Synthesis of Conjugated Triynes via Alkyne Metathesis

doi.org/10.26434/chemrxiv.8342534.v1

Synthesis of Conjugated Triynes via Alkyne MetathesisRomane Manguin, Idriss Curbet, Anthony Clermont, Alexandre Quelhas, Daniel S. Müller, Thierry Roisnel,Olivier BASLE, Yann Trolez, Marc MAUDUIT

Submitted date: 28/06/2019 • Posted date: 28/06/2019Licence: CC BY-NC-ND 4.0Citation information: Manguin, Romane; Curbet, Idriss; Clermont, Anthony; Quelhas, Alexandre; Müller, DanielS.; Roisnel, Thierry; et al. (2019): Synthesis of Conjugated Triynes via Alkyne Metathesis. ChemRxiv. Preprint.

The synthesis of conjugated triynes by molybdenum-catalyzed alkyne metathesis is reported. Strategic to thesuccess of this approach is the utilization of sterically-hindered diynes that allowed the site-selective alkynemetathesis to produce the desired conjugated triyne products. The steric hindrance of alkyne moiety wasfound to be crucial in preventing the formation of diyne byproducts. This novel synthetic strategy wasamenable to self- and cross-metathesis providing straightforward access to the corresponding symmetricaland dissymmetrical triynes with high selectivity (up to 98%).

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https://chemrxiv.org/authors/Olivier_BASLE/6709844

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https://chemrxiv.org/authors/Marc_MAUDUIT/6885695

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Synthesis of Conjugated Triynes via Alkyne Metathesis. Romane Manguin,†⊥ Idriss Curbet,†⊥Anthony Clermont,†⊥Alexandre Quelhas,† Daniel S. Müller,† Thier-ry Roisnel,† Olivier Baslé,‡† Yann Trolez*† and Marc Mauduit*† † Univ Rennes, Ecole Nationale Supérieure de Chimie de Rennes, CNRS, ISCR UMR 6226, F-35000 Rennes, France Supporting Information Placeholder

ABSTRACT: The synthesis of conjugated triynes by molybdenum-catalyzed alkyne metathesis is reported. Strategic to the success of this approach is the utilization of sterically-hindered diynes that allowed the site-selective alkyne metathesis to produce the desired con-jugated triyne products. The steric hindrance of alkyne moiety was found to be crucial in preventing the for-mation of diyne byproducts. This novel synthetic strategy was amenable to self- and cross-metathesis providing straightforward access to the corresponding symmet-rical and dissymmetrical triynes with high selectivity (up to 98%).

Polyynes are an important class of natural products which display a broad array of biological activities such as antibacterial, antimicrobial, antitumor and anticancer properties.1 Conjugated diynes and triynes (e.g. ivorenolide B 12 and ichthyothereol 23) represent the major part of this class of compounds that can be isolat-ed from plants, fungi or bacteria (Figure 1, a). While the diyne core is easily accessible,4 the triyne moiety ap-pears more difficult to access and represents a synthetic challenge.5 Several methods have been developed to access symmetrical and unsymmetrical triynes.6 For instance, Tykwinski recently reported an elegant synthet-ic strategy involving a Pd-catalyzed cross-coupling be-tween 3 and various terminal alkynes that lead to the desired triynes 4 (Figure 1, b).7 Despite the mentioned advances in this field, the development of versatile and efficient methodologies is still necessary.

Figure 1. (a) Examples of natural products containing diynes and triynes. (b) Synthesis of triynes as reported by Tykwinski and co-workers.

Several well-defined Mo- and W-based catalysts (e.g. Cat-1 and Cat-2, Figure 2) can promote metathesis reactions of alkynes, allowing for the formation of new carbon-carbon triple bonds.8 Logically, extension of this methodology to diyne substrates would represent a promising and straightforward way to synthesize the highly desirable 1,3,5-hexatriyne core. This strategy was recently attempted by Tamm and co-workers using a tungsten-alkyne complex Cat-1, which unexpectedly led to the exclusive formation of symmetrical diynes (e.g. 5) and related dimethyldiacetylene 7 (Figure 2, a). Figure 2. Previous works on diynes metathesis catalyzed by Mo- or W-catalysts and the proposed concept for the access of conjugated triynes (this work)

Ivorenolide B 1

Me O

HO

(-)-Ichthyothereol 2

Br Br

OTfiPr3Si

3

H Ar

P(tBu)3/CuI (20 mol%)

Pd(OAc)2 (10 mol%)

iPr2NH

b)

a)

4

Ar

iPr3Si

O

O

OH

O

R2

(1.0 equiv)

(4.0 equiv)

+(62 to 91% yield)

Cat-1 (2 mol %)

CH2Cl2, rt

(b) Cross-Metathesis (Tamm, 2013 & 2018)

(a) Self-Metathesis (Tamm, 2012)

MeCat-1 (2 mol %)

toluene, rt, 2 hMS 5 Å

+Me Me

6 (97% yield)

7 (DMDA)

Cat-2

5

MoPh3SiO

Ph3SiOOSiPh3

W(tBuO)3SiO

(tBuO)3SiOOSi(OtBu)3

Cat-1 Cat-2

O

O

Et

Me

OTBS

O

O

OTBSEtCat-2 (40 mol%)

toluene, rt, 22 hMS 4 Å / 5 Å

9 (82% yield)

(c) Ring-Closing Metathesis (Fürstner, 2015)

( )2

8

Me+

Me?

R1 = R2 or R1 = R2

p-MeOPhPh

R1 R1

R2R1 R2

R1 = Ar or alkyl; R2 = n-Bu or SiMe3

+

R1 Me

R2Me

(d) This work: Alkyne metathesis with sterically-demanding diynes

R1 R2

The anticipated conjugated triynes could not be isolat-ed.9 In 2013, the authors extended the methodology to diyne cross-metathesis (DYCM) (Figure 2, b)10,11 result-ing in unsymmetrical diynes products along with traces of the triyne products upon prolonged reaction time. In line with these pioneering works, Fürstner and cowork-ers also observed a similar reactivity in the catalytic ring-closing metathesis (RCM) of a bis-diyne 8 with molybdenum-alkyne complex Cat-2 that produced the corresponding cyclized diyne 9 (Figure 2, c), a key in-termediate in the total synthesis of Ivorenolide B 1 (Fig-ure 1).12 In order to enforce the appropriate CºC triple bond to react, it was hypothesized that the introduction of bulky groups would influence the regioselectivity13 of diyne metathesis reactions favoring the triyne products over the diyne products as previously reported (Figure 2, d).9-12 We would like now to report on a methodology that allows for the unprecedented selective formation of symmetrical and dissymmetrical conjugated triynes from alkyne metathesis. Investigations began with the synthesis of diynes 13a-c bearing various bulky substituents following a robust methodology from the literature (Scheme 1).14 Starting from terminal alkynes 10, the Pd-catalyzed Sonogashira coupling with (E)-1,2-dichloroethylene 11 resulted in the corresponding chloro-enynes 12. The latter was then reacted with n-Buli and iodomethane to produce the expected diynes 13 in moderate to good yield (Scheme 1). Additionally, structures of diynes 13b and 13c were confirmed by single crystal X-ray diffraction studies (Scheme 1).15 The reactivity and behavior of these steri-cally-demanding diynes were then assessed in alkyne self-metathesis (Table 1).

Scheme 1. Synthetic access of sterically-demanding dienes 13a-c.

a Isolated yield after silica gel purification.

Triisopropylsilylpentadiyne 13a was partially trans-formed into the highly desired triyne 14 upon exposure to alkyne metathesis catalyst Cat-2 at 20 °C for over one hour (Table 1, entry 1, 57% conv.). Nevertheless, albeit triyne 14 was the major product, symmetrical diyne 15 was also obtained in a respective ratio of 74:26 (see Supplementary Information, SI for details). Furthermore, NMR spectroscopy and GC analysis indicated the for-mation of a side product (<5%) identified as dissymmet-rical diyne 16a resulting from the metathesis of 13a with Cat-2 (see scheme 4 and SI for details). In line with the observed moderate conversion and low 17% GC yield of triyne 14, the existing equilibrium with the co-metathesis product 2-butyne was suspected to enhance catalyst decomposition, as a significant amount of Ph3SiOH was detected (see scheme 4 and SI for details). Fortunately, as described by Fürstner and co-workers,12

the addition of 5 Å molecular sieves in the reaction me-dia to trap 2-butyne could increase the conversion up to 91% (Table 1, entry 2). Interestingly, the addition of molecular sieves also improved the triyne/diyne ratio to 83:17 and the desired triyne 14 was formed in 28% yield. Since GC analysis of the crude mixture did not indicate other side products, it was suspected that this loss of material was due to the competitive formation of higher molecular weight polyynes.16 It is noteworthy that the GC yield of triyne 14 was significantly im-proved (47%, entry 3) when a mixture of 4 and 5 Å mo-lecular sieves was used12 without affecting the 85:15 triyne/diyne selectivity. The conditions were then forced by performing the reaction at 80 °C for over 3h. Never-theless, no improvement was observed as the triyne was isolated in a moderate 37% isolated yield after silica gel purification (see SI for details). Table 1. Self-metathesis of triisopropylsilyl-diyne 13a catalyzed by Mo-complex Cat-2a

entry additive Conv.

(%)b Yield of 14 (%)b Ratio 14:15

1 - 57 17 74:26

2 MS 5Å 91 28 83:17

3 MS 4Å + MS 5Å 86 47 85:15

aReaction conditions: Diyne (0.05 mmol), catalyst (0.005 mmol), additive (50 mg), toluene (1 mL), under Ar. bDe-termined by GC-analysis with acetophenone as the external standard.

R H ClCl+

11 (3 equiv)

RCl

PdCl2(PPh3)2 (5 mol%)CuI( 10 mol%)

HN(iPr)2 (5 equiv)THF, 50 °C, 14 h

nBuLi (2 equiv)THF, 0 °C

then MeI (4.5 equiv)rt, 16 h

R Me

10

13

12

Si Me

13a (91%)a

Me

13b (19%)a X-ray of 13b

X-ray of 13c

MePh

PhPh

13c (52%)a

Cat-2 (20 mol%)

toluene, 20 °C, 1 h

14Si Me

13a

1516a (trace)

+

Si Si

SiSi

Si Ph(pOMe)

Furthermore, the stability of triyne 14 toward the Mo-benzylidyne catalyst was evaluated, as the partial cover-sion of triyne to diyne 15 was suspected. After 3 h at 80 °C in the presence of 20 mol % of Cat-2, up to 86 % of triyne 14 was recovered and only traces of diyne 16a (<5%) could be detected (see SI for details). After demonstrating that the presence of a bulky triiso-propylsilyl (TIPS) group allowed for the formation of the triyne as the major metathesis product, it was inves-tigated whether a less sterically-hindered substituent such as a trimethylsilyl (TMS) group would give prefer-entially rise to the diyne or the triyne product. Hence, diyne 17 was synthesized according to a protocol from the literature and exposed it to the aforementioned con-ditions (Scheme 2).17 Mo-based complex Cat-2 ap-peared quite productive, although favoring diyne 19 over triyne 18 (ratio of 18:19 = 7:93), which is consistent with previous observation of the Tamm group (Scheme 1b).11

Scheme 2. Self-metathesis of trimethylsilyl-substituted diyne 17 catalyzed by Mo-complex Cat-2.

aDetermined by GC-analysis with acetophenone as the external stand-ard. Encouraged by the promising good result reached with TIPS substituent, whether the selectivity towards the triyne product could be further improved in the presence of other bulky substituents such as mesityl (Mes) or triphenylmethyl (trityl) groups was investigated (Scheme 3). To our delight, as seen with the TIPS-substrate 13a, Cat-2 demonstrated efficient catalytic activity in the self-metathesis of the mesityl-substituted diyne 13b resulting in the desired triyne product 20 with good 81% selectivity (Scheme 3, a). Importantly, GC-MS analysis evidenced some traces (2%) of tetrayne 22,18 confirming the formation of higher polyynes as aforementioned with the self-metathesis of TIPS-diyne 13a. Interestingly, Mo-benzylidyne catalyst was also efficient toward trityl-substituted diyne 13c affording the expected triyne 23 in 51% isolated yield (Scheme 3, b). The absence of other products as evidenced by the >98:2 triyne:diyne ratio determined by 13C-NMR19 analyses, (see SI for details), highlighted the correlation between improved selectivity and increase of the steric hindrance. X-ray diffraction analysis unambiguously confirmed the structure of trityl-substituted triyne 2315 exhibiting usual geometrical features for this kind of compounds (Figure 3).20 It is notable that, due to the significant catalyst loading, some traces of diynes 16b,c were also observed

resulting from the metathesis of starting materials with Cat-2 (see Scheme 3, a-b and SI for details). The more challenging cross-metathesis reaction was then studied. First, by reacting TIPS- and Mes-diynes 13a and 13b, the formation of the highly desirable dissymmetrical triyne 25 as the major product was observed, reaching up to 39.5% yield (Scheme 3, c). Unsurprisingly, some amounts of symmetrical triynes 14 and 20 were also observed (19 and 11%, resp.), as well as the dissymmet-rical diyne 26 (4%) and its symmetrical congeners 15 and 21 (3 and 9%, resp.). Secondly, with trityl-diyne 13c as a partner, TIPS-diyne 13a led to the expected dis-symmetrical triyne 27 in 47% isolated yield while Mes-diyne 13b produced the corresponding asymmetric tri-yne 2 in 38% isolated yield (Scheme 3, d and e). Scheme 3. Scope of self- and cross-metathesis cata-lyzed by Mo-complex Cat-2.

aDetermined by GC-analysis with acetophenone as the external stand-ard. bBased on the recovering starting material. cIsolated yield after silica gel chromatography. dBased on 13C NMR spectroscopy. eIsolat-ed as an inseparable mixture of 20 + 21 (ratio = 60/40).

Cat-2 (20 mol%)


18Si Me

17

Si Si

19Si Si

+MS 4Å/5Å

88% conv.a

yield of 19 = 74%aratio 18:19 = 7:93a

(a)

Si Me

13a (1 equiv.)

13b (1 equiv.)

Cat-2 (20 mol%)


MS 4Å/5Å

>97% conv.a

(c)

Si Mes25 (39.5%)a

+ 14 (19%)a, 20 (11%)a

+

13a (1 equiv.)

13c (1 equiv.)

Cat-2 (20 mol%)

toluene, 20 °C, 3 hMS 4Å/5Å(d) Si

27 (47%)c

+

MePh

PhPh

Me

13b

MesMes21 (10%)a

Cat-2 (20 mol%)

toluene, 20 °C, 3 hMS 4Å/5Å

72% conv.a20 (49%)a

(b)

+

Ph

PhPh

Me

MePh

PhPh 13c (1 equiv.)

13b (1 equiv.)

Cat-2 (20 mol%)


(e)Ph

PhPh

Mes

28 (38%)c

+

Me+ 20 (16%)e, 21 (17%)e, 23 (29%)c

Mes Mes

22 (2%)a

+

MesMes2

Mes

26 (4%)a

Si

Cat-2 (20 mol%) 23 (51%)c

MePh

PhPh

13c

PhPh

Ph

Ph

PhPh

24 (not detected)d

PhPh

Ph Ph

PhPh

+


94% conv.b

+

+ 15 (3%)a, 21 (9%)a

+ 14 (11%)c , 23 (17%)c

R Ph(pOMe)16b (R = Mes)16c (R = Trityl)

Si Me

>98% conv.

>98% conv.

Figure 1. Solid-state structures of symmetrical triyne 23 (top) and dissymmetrical triynes 27 (down, left) and 28 (down, right) from single crystal X-ray diffraction.

Again, some amounts of symmetrical triynes/diynes were also formed. Furthermore, solid-state structures of these challenging dissymmetrical triynes were also con-firmed by X-ray diffraction analysis (Figure 3). Considering the aforementioned experimental results, a plausible reaction pathway for the self-metathesis of sterically-hindered diynes is suggested in Scheme 4. Depending on the steric hindrance brought by the RL-substituent of the diyne, and according to the established mechanism of the alkyne metathesis,21,9-11 a catalytic cycle could be envisioned. If RL is large enough, Mo-based complex Cat-2 reacts preferably with the d,g - CC triple bond to form the metallacyclobutadiene IA leading to active species IA-1. The latter is then engaged through the catalytic cycle of Scheme 4 to produce the valuable symmetrical (g,g)-triyne. In opposition, if the Mo-catalyst reacts with the more sterically-hindered a,b-alkyne, a catalytic cycle already described by Tamm and co-workers is involved and explains the formation of the diyne product.11 In conclusion, it was demonstrated herein that the utili-zation of sterically-hindered diynes can modify the se-lectivity of alkyne metathesis to favor the formation of the desired triynes. Therefore, the first synthesis of symmetrical and dissymmetrical conjugated triynes by self- and cross-metathesis was successfully achieved. By involving an efficient molybdenum benzylidyne com-plex, remarkable triyne:diyne ratios were obtained (up to >98:2) in good isolated yields (up to 51%). These pio-neer results pave the way to further developments with the quest of more efficient alkyne-metathesis complexes for higher productivity. Notably, the synthesis of more sophisticated (highly functionalized) triyne frameworks that are ubiquitous in a wide range of natural products will be targeted in the future.

ASSOCIATED CONTENT Supporting Information The Supporting Information is available free of charge on the ACS Publications website.

Scheme 4. Proposed mechanisms for the self-metathesis of sterically-hindered diynes catalyzed by Mo-complex Cat-2 leading to conjugated triynes.a

a Reversibility is expected for each step. Only productive metathesis are represented.

NMR spectra of products, GC analyses, experimental procedures and single crystal X-ray crystallographic (PDF) X-ray crystallographic data (CIF)

AUTHOR INFORMATION Corresponding Author * E-mail: [email protected] * E-mail: [email protected] ⊥These authors contributed equally to this work

ORCID Olivier Baslé: 0000-0002-4551-473X Yann Trolez: 0000-0002-5421-9556 Marc Mauduit : 0000-0002-7080-9708

Present Address ‡ LCC-CNRS, Université de Toulouse, CNRS, Toulouse, France Notes The authors declare no competing financial interests.

ACKNOWLEDGMENT We are grateful to the Centre National de la Recherche Scientifique (CNRS), the Ecole Nationale Supérieure de

Me RL+

(Ph3SiO)3MoPhOp-Me

RL

(Ph3SiO)3MoPh(p-OMe)

RL

Me

Me

(Ph3SiO)3Mo Ph(p-OMe)

favoredunfavored

(Ph3SiO)3Mo Me

decomposition

Ph3SiOH

(Ph3SiO)3MoMe

Me

RL

Me Me (Ph3SiO)3Mo RL

(Ph3SiO)3Mo

RL

Me

RL

RLRL

Me RL

RL(p-MeO)Ph

RL Me

cat-2

αβδ γ

δ γ

αβ

IA

IB

IA-1

IA-2

IA-3

IA-4

α β δγ

αβδ γ

δγγδ

δ

δ

δδ γ

γ

γ γ

γ

Chimie de Rennes (ENSCR, grant to RM and AC) and the Ministère de l’Enseignement Supérieur, de la Recherche et de l’Innovation (MESRI, grant to RM and AQ). This work was also supported by the region Bretagne (SAD 2016 N° 9639 – RZSELECT; grant to DSM) and the FASO (grant to IC and DSM). Prof. A. Fürstner is acknowledged for the generous gift of molybdenum benzylidyne complex.

REFERENCES (1) For a recent review, see: Shi Shun, A. L. K.; Tykwinski, R. R.

Synthesis of Naturally Occurring Polyynes. Angew. Chem. Int. Ed. 2006, 45, 1034–1057.

(2) Wang, Y.; Liu, Q.-F.; Xue, J.-J.; Zhou, Y.; Yu, H.-C.; Yang, S.-P.; Zhang, B.; Zuo, J.-P.; Li, Y.; Yue, J.-M. Ivorenolide B, an Immu-nosuppressive 17-Membered Macrolide from Khaya Ivorensis: Struc-tural Determination and Total Synthesis. Org. Lett. 2014, 16, 2062–2065.

(3) Cascon, S. C.; Mors, W. B.; Tursch, B. M.; Aplin, R. T.; Durham, L. J. Ichthyothereol and Its Acetate, the Active Polyacety-lene Constituents of Ichthyothere terminalis (Spreng.) Malme, a Fish Poison from the Lower Amazon. J. Am. Chem. Soc. 1965, 87, 5237–5241

(4) For a recent review, see: Shi, W.; Lei, A. 1,3-Diyne Chemistry: Synthesis and Derivations. Tetrahedron Lett. 2014, 55, 2763–2772.

(5) For a recent review, see:Jevric, M.; Nielsen, M. B. Synthetic Strategies for Oligoynes. Asian J. Org. Chem. 2015, 4, 286–295.

(6) Jahnke, E.; Tykwinski, R. R. The Fritsch–Buttenberg–Wiechell Rearrangement: Modern Applications for an Old Reaction. Chem. Commun. 2010, 46, 3235–3249.

(7) Azyat, K.; Jahnke, E.; Rankin, T.; Tykwinski, R. R. Synthesis of Tri- and Tetraynes Using a Butadiynyl Synthon. Chem. Commun. 2009, 433–435.

(8) (a) Fürstner, A. Alkyne Metathesis on the Rise. Angew. Chem. Int. Ed. 2013, 52, 2794–2819; (b) Ehrhorn, H.; Tamm, M. Well-Defined Alkyne Metathesis Catalysts: Developments and Recent Applications. Chem. Eur. J. 2019, 25, 3190–3208.

(9) Lysenko, S.; Volbeda, J.; Jones, P. G.; Tamm, M. Catalytic Me-tathesis of Conjugated Diynes. Angew. Chem. Int. Ed. 2012, 51, 6757–6761.

(10) Li, S. T.; Schnabel, T.; Lysenko, S.; Brandhorst, K.; Tamm, M. Synthesis of Unsymmetrical 1,3-Diynes via Alkyne Cross-Metathesis. Chem. Commun. 2013, 49, 7189–7191.

(11) Schnabel, T. M.; Melcher, D.; Brandhorst, K.; Bockfeld, D.; Tamm, M. Unraveling the Mechanism of 1,3-Diyne Cross-Metathesis Catalyzed by Silanolate-Supported Tungsten Alkylidyne Complexes. Chem. Eur. J. 2018, 24, 9022–9032.

(12) (a) Ungeheuer, F.; Fürstner, A. Concise Total Synthesis of Ivorenolide B. Chem. Eur. J. 2015, 21, 11387–11392; (b) Schaubach, S.; Gebauer, K.; Ungeheuer, F.; Hoffmeister, L.; Ilg, M. K.; Wirtz, C.; Fürstner, A. A Two-Component Alkyne Metathesis Catalyst System with an Improved Substrate Scope and Functional Group Tolerance: Development and Applications to Natural Product Synthesis. Chem. Eur. J. 2016, 22, 8494–8507. For pioneer development of Mo-

akylidyne Cat-2, see: c) Heppekausen, J.; Stade, R.; Goddard, R.; Fürstner, A. Practical New Silyloxy-Based Alkyne Metathesis Cata-lysts with Optimized Activity and Selectivity Profiles. J. Am. Chem. Soc. 2010, 132, 11045–11057 d) Heppekausen, J.; Stade, R.; Kondoh, A.; Seidel, G.; Goddard, R.; Fürstner, A. Optimized Synthesis, Struc-tural Investigations, Ligand Tuning and Synthetic Evaluation of Silyloxy-Based Alkyne Metathesis Catalysts. Chem. Eur. J. 2012, 18, 10281–10299.

(13) We previously reported that sterically-hindered alkynes could promote high regioselectivity in asymmetric conjugate addition of enynones, see: Tissot, M.; Poggiali, D.; Hénon, H.; Müller, D.; Gué-née, L.; Mauduit, M. ; Alexakis, A. Formation of Quaternary Stereo-genic Centers by NHC-Cu-Catalyzed Asymmetric Conjugate Addi-tion Reactions with Grignard Reagents on Polyconjugated Cyclic Enones. Chem. Eur. J. 2012, 18, 8731–8747.

(14) (a) Métay, E.; Hu, Q.; Negishi, E. Highly Efficient and Selec-tive Synthesis of Conjugated Triynes and Higher Oligoynes of Bio-logical and Materials Chemical Interest via Palladium-Catalyzed Alkynyl−Alkenyl Coupling. Org. Lett. 2006, 8, 5773–5776; (b) Ker-isit, N.; Ligny, R.; Gauthier, E. S.; Guegan, J.-P.; Toupet, L.; Guille-min, J.-C.; Trolez, Y. Synthesis and Reactivity of 5-Bromopenta-2,4-diynenitrile (BrC5N) an Access to π-Conjugated Scaffolds. Helv. Chim. Acta. 2019, 102, e1800232.

(15) CCDC-1908077 (diyne 13b), CCDC-1908076 (diyne 13c), CCDC-1908075 (triyne 23), CCDC-1915266 (triyne 27) and CCDC-1920652 (triyne 28) contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from The Cambridge Crystallographic Data Centre via: www.ccdc.cam. ac.uk/data_request/cif.

(16) The generation of higher polyynes in such processes was pre-viously reported by Tamm, see ref. 10. Macrocyclic polyynes were also reported, see: Gross, D. E.; Moore, J. S. Arylene–Ethynylene Macrocycles via Depolymerization–Macrocyclization. Macromole-cules 2011, 44, 3685–3687.

(17) Fiandanese, V.; Bottalico, D.; Marchese, G.; Punzi, A. Syn-thesis of Naturally Occurring Polyacetylenes via a Bis-Silylated Diyne. Tetrahedron 2006, 62, 5126–5132.

(18) Tetrayne 22 resulted from the self-metathesis of triyne 20. (19) Due to their higher molecular weight, the alkyne metathesis of

trityl-diynes were monitored by 13C-NMR spectroscopy instead of GC analysis.

(20) Chalifoux, W. A.; Tykwinski, R. R. Synthesis of polyynes to model the sp-carbon allotrope carbyne. Nat. Chem. 2010, 2, 967–971.

(21) Katz, T. J.; McGinnis, J. Mechanism of the Olefin Metathesis Reaction. J. Am. Chem. Soc. 1975, 97, 1592–1594.

6

MoPh3SiOPh3SiO

OSiPh3

Mo-catalyst

p-MeOPh

R1 = R2 or R1 = R2

+

R1 Me

R2Me

R1 R2

sterically-hindered diynes

(R1, R2 = TIPS, trityl, mesityl)

Self- and Cross-alkyne metathesis

6 examplesup to 98% selectivity

38 to 51% yields

download fileview on ChemRxivTriynes 2019.pdf (823.78 KiB)



1

SupportingInformation

Synthesisofconjugatedtriynesviaalkynemetathesis

RomaneManguin,†⊥IdrissCurbet,†⊥AnthonyClermont,†⊥AlexandreQuelhas,†DanielS.Müller,†ThierryRoisnel,§OlivierBaslé,†YannTrolez*†andMarcMauduit*†

†UnivRennes,EcoleNationaleSupérieuredeChimiedeRennes,CNRS,ISCR–UMR6226,F-35000Rennes,France.E-mail:[email protected];[email protected]

Table of contents

I- General.............................................................................................................................3

II- Reagents...........................................................................................................................4

III- Synthesisofdiynesubstrates...........................................................................................5

SynthesisofTriisopropyl(penta-1,3-diynyl)silane(13a)........................................................5

Twostepsynthesisof1,3,5-trimethyl-2-(penta-1,3-diyn-1-yl)benzene(13b).......................5

Twostepsynthesisofhexa-2,4-diyne-1,1,1-triyltribenzene(13c).........................................6

Synthesisoftriisopropyl((4-methoxyphenyl)buta-1,3-diyn-1-yl)silane(16a).........................7

IV- Mo-catalyzedself-metathesisofdiynes...........................................................................9

Self-metathesisofTIPS-diyne13a(Table1)...........................................................................9

Synthesisofbis-triisopropylsilylhexatriyne(14)...................................................................14

Self-metathesisofTMS-diyne17(Scheme2):......................................................................14

Synthesisof1,1,1,8,8,8-hexaphenylocta-2,4,6-triyne(23)(Scheme3)................................17

V- Mo-catalyzedcross-metathesisofdiynes......................................................................18

Cross metathesis of triisopropyl(penta-1,3-diyn-1-yl)silane (13a) and 1,3,5-trimethyl-2-(penta-1,3-diyn-1-yl)benzene(13b)(Scheme3)..................................................................18

Crossmetathesisoftriisopropyl(penta-1,3-diyn-1-yl)silane(13a)andhexa-2,4-diyne-1,1,1-triyltribenzene(13c)(Scheme3).........................................................................................21

Cross metathesis of 1,3,5-trimethyl-2-(penta-1,3-diyn-1-yl)benzene (13b) and hexa-2,4-diyne-1,1,1-triyltribenzene(13c)(Scheme3)......................................................................22

VI- Stabilitystudyof14towardtheMo-benzylidynecatalystCat-2...................................23

VII- NMRspectra...................................................................................................................24

2

VIII- X-RayCrystallographicdata............................................................................................35

X-raystructureoftriyne23..................................................................................................35

X-raystructureofdiyne13c.................................................................................................36

X-raystructureofdiyne13d.................................................................................................37



3

I- General

Reactions were monitored by thin-layer chromatography (TLC) carried out on silica gel plates

(60F254) using UV light as visualizing agent and by staining with KMnO4. Column

chromatography was performed with silica gel (spherical, particle size 40 µm, neutral). 1H (400

MHz) and 13C (101 MHz) NMR spectra were recorded on a Bruker 400 NMR spectrometer

with complete proton decoupling for nucleus other than 1H. Chemical shifts are reported in

parts per million with the solvent resonance as the internal standard (CDCl3: 1H, δ 7.26 ppm; 13C, δ 77.16 ppm; CD2Cl2: 1H, δ 5.30 ppm; 13C, δ 55.52 ppm). Coupling constants (J) are

reported in hertz (Hz). Multiplicities are reported using following abbreviations: s = singlet, d

= doublet, m = multiplet. Solvents: Tetrahydrofuran and toluene were purified using MBraun

MB-SPS-5 Solvent Purification System and typically contained <15 ppm of H2O (verified by

Karl Fischer titration). Solvents used for catalysis were freeze-pump-thaw degassed prior to

use. All commercial chemicals were used as received unless otherwise noted. CDCl3 was

purchased from Euriso-Top company and used as received.

4

II- Reagents

Starting materials and products:

• (E)-(2-chlorovinyl)triisopropylsilane 12a was prepared according to the literature.[1]

• Triisopropyl((4-methoxyphenyl)buta-1,3-diynyl)silane (16a) was prepared according to the

literature to serve as a reference for gas chromatographic analysis.[2]

• The synthesis of 1,4-bis(triisopropylsilyl)buta-1,3-diyne (15) was described in the

literature.[3]

• Prop-2-yne-1,1,1-triyltribenzene (10c) was prepared according to the literature.[4]

• Trimethyl(penta-1,3-diynyl)silane (17) was prepared according to the literature.[5]

• 1,4-bis(trimethylsilyl)buta-1,3-diyne (19) is commercially available. CAS: 4526-07-2.

• 2-ethynyl-1,3,5-trimethylbenzene (10b) is commercially available. CAS: 769-26-6.

• The Mo-based complex Cat-2 was synthesized by the Prof. A. Fürstner group according to

the literature.[6]

5

III- Synthesis of diyne substrates

Synthesis of Triisopropyl(penta-1,3-diynyl)silane (13a)

To a solution of freshly prepared (E)-(2-

chlorovinyl)triisopropylsilane 12a (539 mg, 6.0 mmol, 1.0 equiv) in

THF (25 mL) was added n-BuLi (7.5 mL, 12.0 mmol, 2.0 equiv; 1.6

M solution in hexanes) at 0 °C and the solution was stirred for 1

hour at 0 °C. Then a solution of iodomethane (3.83 g, 27.0 mmol,

4.5 equiv) in THF (5 mL) was added drop wise to the reaction mixture at 0 °C. The mixture

was stirred at room temperature for 16 h and then quenched by the addition of a saturated

aqueous solution of NH4Cl (40 mL). The aqueous layer was extracted with Et2O (2 ´ 40 mL)

and the combined organic layers were washed with brine (40 mL), dried over MgSO4 and

concentrated in vacuo. The resultant residue was purified by flash chromatography (pentane)

to obtain diyne 13a as a pale-yellow oil (1.21 g, 5.48 mmol, 91% yield). Rf = 0.91(pentane).

1H-NMR (400 MHz, CDCl3): δ 1.93 (s, 3 H), 1.07 (s, 21 H). 13C-NMR (101 MHz, CDCl3): δ

90.2, 79.7, 74.7, 65.3, 18.7, 11.4, 4.4. GC-MS (m/z fragments observed): 220.1, 177.0, 149.1,

135.0, 121.1, 107.0.

Two step synthesis of 1,3,5-trimethyl-2-(penta-1,3-diyn-1-yl)benzene (13b)

1) Synthesis of (E)-2-(4-chlorobut-3-en-1-yn-1-yl)-1,3,5-trimethylbenzene (12b)

Argon gas was bubbled through a solution of acetylene 10b (1.37

g, 9.5 mmol, 1.0 equiv), dichloroethylene (2.2 mL, 28.5 mmol, 3.0

equiv), PdCl2(PPh3)2 (333 mg, 0.48 mmol, 0.05 equiv), and

diisopropylamine (6.5 mL, 47.5 mmol, 5.0 equiv) in THF (150 mL)

for 10 minutes. CuI (183 mg, 0.95 mmol, 0.1 equiv.) was added at

rt and the mixture was heated to 50 °C for 14 hours. Then heating was stopped and once the

reaction mixture reached rt it was filtered through a pad of silica gel and thoroughly rinsed with

pentane. The desired compound 12b was obtained after purification by column chromatography

(pure pentane) as a white solid (1.07 g, 5.22 mmol, 55 % yield).

6

1H NMR (400 MHz, CDCl3): δ 6.87 (s, 2 H), 6.59 (d, J = 13.6 Hz, 1 H), 6.23 (d, J = 13.6 Hz,

1 H), 2.37 (s, 6 H), 2.28 (s, 3 H). 13C NMR (101 MHz, CDCl3): δ 140.4, 138.4, 129.0, 127.8,

119.5, 114.5, 91.9, 90.1, 21.5, 21.0 HRMS (ESI) m/z calcd. for C13H1435Cl [M+H]+ 205.07785,

found 205.0782 (2ppm).

2) Synthesis of 1,3,5-trimethyl-2-(penta-1,3-diyn-1-yl)benzene (13b)

To a solution of 12b (1.07 g, 5.2 mmol, 1 equiv.) in THF (75 mL)

was added n-BuLi (6.5 mL, 10.4 mmol, 2 equiv.; 1.6 M solution in

hexanes) at 0 °C and the solution was stirred for 1 hour at 0 °C. Then

a solution of iodomethane (3.25 mL, 52.2 mmol, 10 equiv.) in THF

(5 mL) was added dropwise to the reaction mixture at 0 °C. The

mixture was stirred at room temperature for 16 h and then quenched by the addition of a

saturated aqueous solution of NH4Cl (40 mL). The aqueous layer was extracted with Et2O (2 ´

20 mL) and the combined organic layers were washed with brine (20 mL), dried over MgSO4

and concentrated in vacuo. The resultant residue was purified by flash chromatography (pure

pentane) to obtain diyne 13b as yellow crystals (325 mg, 1.78 mmol, 34% yield). 1H-NMR (400 MHz, CDCl3): δ 6.84 (s, 2 H), 2.39 (s, 6 H), 2.27 (s, 3 H), 2.04 (s, 3 H). 13C

NMR (101 MHz, CDCl3): δ 144.3, 138.2, 128.5, 118.8, 79.5, 70.3, 70.1, 68.5, 21.4, 21.0, 4.3

HRMS (ESI) m/z calcd. for C14H15 [M+H]+ 183.1168, found 183.1168.

Two step synthesis of hexa-2,4-diyne-1,1,1-triyltribenzene (13c)

1) Synthesis of (E)-(3-chloroprop-2-ene-1,1,1-triyl)tribenzene (12c)

Argon gas was bubbled through a solution of acetylene 10c (608

mg, 2.27 mmol, 1.0 equiv), dichloroethylene (673 mg, 6.94 mmol,

3.0 equiv), PdCl2(PPh3)2 (78.5 mg, 0.11 mmol, 0.05 equiv), and

diisopropylamine (1.16 g, 11.4 mmol, 5.0 equiv) in THF (40 mL)

for 10 minutes. CuI (47 mg, 0.25 mmol, 0.1 equiv.) was added at rt

and the mixture was heated to 50 °C for 14 hours. Then heating was stopped and once the

reaction mixture reached rt it was filtered through a pad of silica gel and thoroughly rinsed with

7

pentane. The desired compound 12c was obtained after purification by column chromatography

(pentane: dichloromethane from 100:0 to 95:5) as a colorless solid (539 mg, 1.64 mmol, 72 %

yield). Rf = 0.45 (95:5 pentane:CH2Cl2). 1H NMR (400 MHz, CDCl3): δ 7.29-7.21 (m, 15 H), 6.58 (d, J = 13.6 Hz, 1 H), 6.09 (d, J =

13.6 Hz, 1 H). 13C NMR (101 MHz, CDCl3): δ 144.8, 129.9, 129.1, 128.1, 127.0, 114.0, 98.2,

93.4, 68.7. HRMS (ESI) m/z calcd. for C23H1835Cl [M+H]+ 329.10915, found 329.1091.

2) Synthesis of hexa-2,4-diyne-1,1,1-triyltribenzene (13c)

To a solution of 12c (539 mg, 1.64 mmol, 1.0 equiv) in THF (25

mL) was added n-BuLi (2.05 mL, 3.27 mmol, 2.0 equiv; 1.6 M

solution in hexanes) at 0 °C and the solution was stirred for 1 hour

at 0 °C. Then a solution of iodomethane (1.05 g, 7.4 mmol, 4.5

equiv) in THF (5 mL) was added drop wise to the reaction mixture

at 0 °C. The mixture was stirred at room temperature for 16 h and then quenched by the addition

of a saturated aqueous solution of NH4Cl (20 mL). The aqueous layer was extracted with Et2O

(2 ´ 20 mL) and the combined organic layers were washed with brine (20 mL), dried over

MgSO4 and concentrated in vacuo. The resultant residue was purified by flash chromatography

(pure pentane) to obtain diyne 13c as a white solid (360 mg, 1.17 mmol, 72% yield). Rf = 0.25

(pentane) 1H-NMR (400 MHz, CDCl3): δ 7.31-7.21 (m, 15 H), 1.96 (s, 3 H). 13C NMR (101 MHz,

CDCl3): δ 144.5, 129.1, 128.1, 127.0, 80.8, 76.4, 70.2, 64.5, 56.1, 4.4. HRMS (ESI) m/z calcd.

for C24H19 [M+H]+ 307.14813, found 307.1481.

Synthesis of triisopropyl((4-methoxyphenyl)buta-1,3-diyn-1-yl)silane (16a)

In a two-neck round-bottom flask under argon, were placed 4-ethylanisole (500 mg, 3.78 mmol,

1 equiv.), water (9 mL), methanol (15 mL), diethyl ether (10 mL) and n-propylamine (1.2 mL).

The solution was degased with argon and CuCl (22 mg, 0.22 mmol, 0.058 equiv.) was added.

A solution of (bromoethynyl)triisopropylsilane (1.283 mg, 4.91 mmol, 1.3 equiv.) in methanol

(10 mL) was added dropwise and the mixture was stirred at room temperature overnight. The

reaction was then quenched with a saturated solution of NH4Cl (20 mL) and the aqueous layer

8

was extracted three times with diethylether. The combined organic layers were washed twice

with brine. The organic layer was dried over MgSO4, filtered and concentrated in vacuo. The

desired compound was obtained after purification by column chromatography (n-pentane:

DCM from 100:0 to 96:4) as white solid in 68 % yield (800 mg, 2.56 mmol). Rf (SiO2, n-

pentane) = 0.34.

1H-NMR (400 MHz, CDCl3): δ 7.45 (d, J = 8.8 Hz, 2 H), 6.84 (d, J = 8.8 Hz, 2 H), 3.81 (s, 3

H), 1.11 (s, 21 H). 13C NMR (101 MHz, CDCl3): δ 160.3, 134.3, 114.1, 113.4, 89.8, 87.0, 75.8,

73.5, 55.3, 18.6, 11.3. Spectral data were consistent with those previously reported.[2]

9

IV- Mo-catalyzed self-metathesis of diynes

Note: All reactions were carried out in a glove-box with degassed solvents. The powdered

molecular sieves Molecular sieves 4 Å (CAS: 70955-01-0; Ref. No. 11424553 Alfa Aesar™)

and) and 5 Å (CAS : 69912-79-4; Ref. No. 10296980 Acros Organics™) were heated with a

heatgun (~ 300 °C for 10 min at 1 mbar) prior to introduction into the glove box.

Self-metathesis of TIPS-diyne 13a (Table 1)

To a one-dram vial charged with a solution of catalyst Cat-2 (5.2 mg, 0.005 mmol, 20 mol %)

in toluene (250 µL) were added powdered molecular sieves 4 Å (50 mg) and powdered

molecular sieves 5 Å (50 mg). Then a solution of TIPS-diyne 13a (11.0 mg, 0.05 mmol, 1.0

equiv) was added and the reaction was stirred at rt for 1 hour. Then the vial was removed from

the glove box and a solution of acetophenone (12.0 mg, 0.10 mmol, 2.0 equiv) in technical

grade EtOAc (1.0 mL) was added. Approximately 100 µL of this solution was removed, filtered

through plug of silica and rinsed with 900 µL of ether. The resulting solution was analyzed by

GC-MS.

• GC-analysis:

Description of GC-method: Instument: Shimadzu GC-2014 Carrier gas: Helium Inlet temperature: 300 °C Pressure: 143.4 kPa Column flow: 1.79 mL / min; 40.6 cm / s Split ratio: 20 External standard: acetophenone (2.0 equiv)

Temperature protocol:

10

Determination of response factors:

¿ Area under Peak of triyne 14 / area under peak of acetophenone

¢ Area under Peak of diyne starting material 13a / area under Peak of acetophenone

p Area under Peak of diyne side-product 15 / area under Peak of acetophenone

Determination of GC conversion and yield:

Triyne 14 (%) = 66.7 * (Area of triyne 14 / area of acetophenone) Diyne 13a (%) = 105.3 * (Area of diyne 13a / area of acetophenone) Diyne 15 (%) = 71.9 * (Area of diyne 15 / area of acetophenone)

entry additive temp.(°C)

time(h)

conv.(%)

b yieldof14(%)

b ratio

14:15b

1 - 20 1 57 17 74:26

2 MS5Å 20 1 91 28 83:17

3 MS4Å+MS5Å 20 1 86 47 85:15

11

• GC-trace of Table 1, entry 1 (without molecular sieves)

Figure S1: GC chromatogram of Table 1, entry 1

Calculation details: Conversion of 13a = 100 – [105.3 * (165616 / 408768)] = 57%

Yield of 14 = 66.7 * (106776 / 408768) = 17%

Ratio 14 / 15 = 106776 / 34007 = 3.14

Table 1 Entry 1 :

12

• GC-trace of Table 1, entry 2 (with powdered molecular sieves 4 Å)

Figure S2: GC chromatogram of Table 1, entry 2


Yield of 14 = 66.7 * (165982 / 393377) = 28%

Ratio 14 / 15 = 165982 / 30574 = 5.43

Table 1 entry 2

13

• GC-trace of Table 1, entry 3 (with powdered molecular sieves 4 Å and 5 Å)

Figure S3: GC chromatogram of Table 1, entry


Yield of 14 = 66.7 * (264088 / 375903) = 47%

Ratio 14 / 15 = 264088 / 44454 = 5.94

Table 1 entry 3

14

Synthesis of bis-triisopropylsilylhexatriyne (14)

A solution containing catalyst Cat-2 (19.5 mg, 0.0187 mmol,

20 mol %) in toluene (1 mL) and molecular sieves (5 beads)

was stirred for 5 minutes at room temperature before a

solution of TIPS-diyne 13a (43.1 mg, 0.196 mmol, 2 equiv.)

in toluene (1 mL) was added. The Schlenk was then closed

and taken out of the glovebox, and heated at 80 °C for 3 hours. The mixture was filtered through

a pad of silica and the filtrate was evaporated. The desired triyne 14 was obtained after

purification by column chromatography (pure pentane) as a white solid (14 mg, 37 %, 0.036

mmol). Rf = 0.95 (n-pentane).

1H NMR (400 MHz, CDCl3): δ 1.08 (s, 42 H). 13C NMR (101 MHz, CDCl3): δ 89.9, 84.6,

61.5, 18.7, 11.4. Spectral data were consistent with those previously reported.[6]

Self-metathesis of TMS-diyne 17 (Scheme 2):

To a one-dram vial charged with a solution of catalyst Cat-2 (5.2 mg, 0.005 mmol, 20 mol %)

in toluene (250 µL) were added powdered molecular sieves 4 Å (50 mg) and powdered

molecular sieves 5 Å (50 mg). Then a solution of TMS-diyne 17 (11.0 mg, 0.05 mmol, 1.0

equiv) was added and the reaction was stirred at rt for 1 hour. Then the vial was removed from

the glove box and a solution of n-dodecane (17.0 mg, 0.10 mmol, 2.0 equiv) in technical grade

EtOAc (1.0 mL) was added. Approximately 100 µL of this solution was removed, filtered

through plug of silica and rinsed with 900 µL of ether. The resulting solution was analyzed by

GC-MS.

Note: Commercial 1,4-bis(trimethylsilyl)buta-1,3-diyne 19 was used to establish the

GC-method.

• GC-analysis:

Description of GC-method: Instument: Shimadzu GC-2014 Carrier gas: Helium Inlet temperature: 280 °C Pressure: 137.7 kPa Column flow: 1.86 mL / min; 40.0 cm / s Split ratio: 20 External standard: n-dodecane (2.0 equiv)

15


Determination of response factors:

¿ Area under Peak of diyne product 19 / area under peak of n-dodecane

¢ Area under Peak of diyne starting material 17 / area under Peak of n-dodecane

Determination of GC conversion and yield:

Diyne 17 (%) = 285.7 * (Area of diyne-SM 17 / area of n-dodecane) Diyne 19 (%) = 232,6 * (Area of diyne 19 / area of n-dodecane)

16

Figure S4: GC chromatogram for metathesis of 17 (Scheme 2)

Calculation details: Conversion of 17 = 100 – [285.7 * (25625 / 618289)] = 88%

Yield of 19 = 232.6 * (195577 / 618289) = 74%

Ratio 18 / 19 = 13163 / 195577 = 0.067

GC for scheme 2

n-do

deca

ne

17

Synthesis of 1,1,1,8,8,8-hexaphenylocta-2,4,6-triyne (23) (Scheme 3)

To a 2-dram vial charged with a solution of catalyst Cat-2

(16.6 mg, 0.016 mmol, 20 mol %) in toluene (1.0 mL) were

added powdered molecular sieves 4 Å (150 mg) and powdered

molecular sieves 5 Å (150 mg). Then a solution of trityl-diyne

13c (49 mg, 0.16 mmol, 2.0 equiv) in toluene (0.5mL) was

added. The vial was sealed and the reaction mixture was stirred for 3 h at room temperature.

The crude reaction mixture was filtered through a pad of silica and the filtrate was evaporated.

The crude mixture was purified by column chromatography (pentane: dichloromethane 90:10)

and the obtained solid was washed with pentane to give the desired triyne 23 as white solid

(22.6 mg, 0.034 mmol, 51 %). Rf = 0.30 (n-pentane). m.p. 280-282 °C.

1H NMR (400 MHz, CDCl3): δ 7.32-7.20 (m, 30 H). 13C NMR (101 MHz, CDCl3): δ 144.0,

129.2, 128.3, 127.4, 84.3, 70.2, 63.3, 56.6. HRMS (ESI) m/z calcd. for C44H31 [M+H]+

558.2342, found 558.2338 (1ppm).

18

V- Mo-catalyzed cross-metathesis of diynes

Note: All reactions were carried out in a glove-box with degassed solvents. The powdered

molecular sieves Molecular sieves 4 Å (CAS: 70955-01-0; Ref. No. 11424553 Alfa Aesar™)

and) and 5 Å (CAS: 69912-79-4; Ref. No. 10296980 Acros Organics™) were heated with a

heatgun (~ 300 °C for 10 min at 1 mbar) prior to introduction into the glove box.

Cross metathesis of triisopropyl(penta-1,3-diyn-1-yl)silane (13a) and 1,3,5-trimethyl-2-(penta-1,3-diyn-1-yl)benzene (13b) (Scheme 3, c)

To a 2-dram vial charged with a solution of catalyst Cat-2 (4.1 mg, 0.0039 mmol, 20 mol %)

in toluene (0.2 mL) were added powdered molecular sieves 4 Å (20 mg) and powdered

molecular sieves 5 Å (20 mg). Then a solution of 13a (4.3 mg, 0.0195 mmol, 1.0 equiv) and

13b (3.6 mg, 0.0195 mmol, 1.0 equiv) in toluene (0.2 mL) was added. The vial was sealed and

the reaction mixture was stirred for 3 h at room temperature. The crude reaction mixture was

filtered through a pad of silica and the filtrate was evaporated. Then, the resulting solution was

analyzed by GC-MS with acetophenone as internal standard. All products were identified and

the results are available in Table S1.

Si Me

13a (1 equiv.)

13c (1 equiv.)

Cat-2 (20 mol%)


MS 4Å/5Å

>97% conv.a

(c)

Si Mes25 (39.5%)a

+ 14 (19%)a, 20 (11%)a

+

MeMes

26 (4%)a

Si+

+ 15 (3%)a, 21 (9%)a

19

• GC-MS analysis:

Description of GC-method: Instument: GC-MS Shimadzu QP2010SE Carrier gas: Helium Inlet temperature: 300 °C Pressure : 79.5 kPa Column flow: 40 cm / s Split ratio: 20 External standard: acetophenone (2.0 equiv)


20

Product GC Yield

3%

3%

9%

4%

19%

9%

1%

40%

11%

Table S1: GC yield obtained for the cross-metathesis of 13a and 13b

21

Figure S5: GC-MS chromatogram obtained for the cross-metathesis of 13a and 13b

Cross metathesis of triisopropyl(penta-1,3-diyn-1-yl)silane (13a) and hexa-2,4-diyne-1,1,1-triyltribenzene (13c) (Scheme 3, d)

To a 2-dram vial charged with a solution of catalyst Cat-2 (47 mg, 0.0454 mmol, 20 mol %) in

toluene (1.5 mL) were added powdered molecular sieves 4 Å (400 mg) and powdered molecular

sieves 5 Å (400 mg). Then a solution of 13a (50 mg, 0.227 mmol, 1.0 equiv) and 13c (69.5 mg,

0.227 mmol, 1.0 equiv) in toluene (0.5 mL) was added. The vial was sealed and the reaction

mixture was stirred for 3 h at room temperature. The crude reaction mixture was filtered through

Scheme 3 entry (c)

Chromatogram :

Peak table :

13a (1 equiv.)

13c (1 equiv.)

Cat-2 (20 mol%)


(d) Si

27 (47%)c

+

MePh

PhPh

Ph

PhPh

+ 14 (11%)c , 23 (17%)c

Si Me

>98% conv.

22


purification by column chromatography (pentane to pentane:dichloromethane 90:10) as white

solid (50.4 mg, 0.106 mmol, 47 %). Rf = 0.60 (n-pentane).

1H NMR (400 MHz, CDCl3): δ 7.36-7.27 (m, 9 H), 7.24-7.18 (m, 6 H), 1.10 (s, 21 H). 13C

NMR (101 MHz, CDCl3): δ 129.2, 128.3, 127.4, 18.7, 11.4. HRMS (ESI) m/z calcd. for

C34H37Si [M+H]+ 472.2581, found 472.2582 (1 ppm).

Note: Along the purification over SiO2, triyne 14 was obtained as a white solid (9.6 mg, 0.025

mmol, 11 %). Triyne 23 was also obtained as a white solid (19 mg, 0.034 mmol, 17 %).

Cross metathesis of 1,3,5-trimethyl-2-(penta-1,3-diyn-1-yl)benzene (13b) and hexa-2,4-diyne-1,1,1-triyltribenzene (13c) (Scheme 3, e)

To a 2-dram vial charged with a solution of catalyst Cat-2 (37 mg, 0.036 mmol, 20 mol %) in

toluene (1 mL) were added powdered molecular sieves 4 Å (130 mg) and powdered molecular

sieves 5 Å (130 mg). Then a solution of 13b (33.1 mg, 0.181 mmol, 1.0 equiv) and 13c (40 mg,

0.181 mmol, 1.0 equiv) in toluene (0.6 mL) was added. The vial was sealed and the reaction

mixture was stirred for 3 h at room temperature. The crude reaction mixture was filtered through


purification by column chromatography (pentane to pentane:dichloromethane 90:10) as yellow

solid (29.7 mg, 0.0683 mmol, 38 %). Rf = 0.75 (pentane:dichloromethane 90:10).

1HNMR(400MHz,CDCl3):δ7.35-7.27(m,10H),7.25-7.20(m,5H),6.88(s,2H),2.42(s,6H),

2.30(s,3H).13CNMR(101MHz,CDCl3):δ143.4,142.3,139.2,128.9,128.0,127.7,117.6,21.3,

20.7.HRMS (ESI) m/z calcd. for C34H27 [M+H]+ 435.21073, found 435.2107.

MePh

PhPh 13c (1 equiv.)

13b (1 equiv.)

Cat-2 (20 mol%)


(e)Ph

PhPh

Mes

28 (38%)c

+

Me+ 20 (16%)e, 21 (17%)e, 23 (29%)c

23

Note: Along the purification over SiO2, triyne 23 was obtained as a white solid (18.8 mg, 0.034

mmol, 29 %). Diyne 21 and triyne 20 were also obtained as a mixture (ratio 20 : 21 = 60 : 40

determined by GC analysis).

VI- Stability study of 14 toward the Mo-benzylidyne catalyst Cat-2

To a Schlenk-flask charged with a solution of catalyst Cat-2 (3.8 mg, 0.004 mmol, 20 mol %)

in toluene (1.0 mL) were added 5 beads of molecular sieves 5 Å. Then a solution of triyne 14

(14 mg, 0.036 mmol, 1.0 equiv) in toluene (1.0 mL) was added and the closed Schlenk-flask

was removed from the glove box and heated at 80 °C for 3 h. The crude reaction mixture was

filtered through a pad of silica and the filtrate was evaporated. NMR spectra of the crude showed

some traces of diyne 16a. The triyne 14 was recovered after purification by column

chromatography (pentane:dichloromethane 90:10) as white solid (12 mg, 0.031 mmol, 86%).

24

VII- NMR spectra

Triisopropyl(penta-1,3-diynyl)silane (13a)

Figure S6:

1H and 13C NMR spectra of 13a in CDCl3

25

(E)-2-(4-chlorobut-3-en-1-yn-1-yl)-1,3,5-trimethylbenzene (12b)

Figure S7:

1H and 13C NMR spectra of 12b in CDCl3

26

Hexa-2,4-diyne-1,1,1-triyltribenzene (13b)

Figure S8:

1H and 13C NMR spectra of 13b in CDCl3

27

(E)-(3-chloroprop-2-ene-1,1,1-triyl)tribenzene (12c)

Figure S9:

1H and 13C NMR spectra of 12c in CDCl3

28

Hexa-2,4-diyne-1,1,1-triyltribenzene (13c)

Figure S10:

1H and 13C NMR spectra of 13c in CDCl3

29

Triisopropyl((4-methoxyphenyl)buta-1,3-diyn-1-yl)silane (16a)

Figure S11:

1H and 13C NMR spectra of 16a in CDCl3

30

Bis-triisopropylsilylhexatriyne (14)

Figure S12:

1H and 13C NMR spectra of 14 in CDCl3

31

1,1,1,8,8,8-hexaphenylocta-2,4,6-triyne (23)

Figure S13:


32

triisopropyl(7,7,7-triphenylhepta-1,3,5-triyn-1-yl)silane (27)

Figure S14: 1H and 13C NMR spectra of 27 in CDCl3

NMR of 27

33

(7-mesitylhepta-2,4,6-triyne-1,1,1-triyl)tribenzene (28)

Figure S15:


NMR of 28

34

Stability study of triyne 14 toward the Mo-benzylidyne catalyst Cat-2

Figure S16:

1H and 13C NMR spectra of stability study of 14 in CDCl3

35

VIII- X-Ray Crystallographic data

X-ray structure of triyne 23

Table S2: Crystal data and structure refinement for 23

Empirical formula C44H30 Formula weight 558.68 g/mol Temperature 150 K Wavelength 0.71073 Å Crystal system, space group triclinic, P -1 Unit cell dimensions a = 9.9378(9) Å, a = 93.791(3) ° b = 9.9882(8) Å, b = 94.905(3) ° c = 17.7699(15) Å, g = 98.931(3) ° Volume 1730.4(3) Å3 Z, Calculated density 2, 1.072 g.cm-3 Absorption coefficient 0.061 mm-1 F(000) 588 Crystal size 0.420 x 0.250 x 0.140 mm Crystal color colourless Theta range for data collection 2.914 to 27.484 ° h_min, h_max -12, 12 k_min, k_max -12, 12 l_min, l_max -23, 23 Reflections collected / unique 41529 / 7909 [R(int) = 0.0434] Reflections [I>2sigma(I)] 6557 Completeness to theta_max 0.999 Absorption correction type multi-scan Max. and min. transmission 0.991 , 0.000 Refinement method Full-matrix least-squares on F^2 Data / restraints / parameters 7909 / 0 / 397 Goodness-of-fit 1.051 Final R indices [I>2sigma(I)] R1 = 0.0457, wR2 = 0.1170 R indices (all data) R1 = 0.0571, wR2 = 0.1244 Largest diff. peak and hole 0.342 and -0.342 e.Å-3

36

X-ray structure of diyne 13c

Table S3: Crystal data and structure refinement for 13c.

Empirical formula C16 H12 Formula weight 204.26 g/mol Temperature 150 K Wavelength 0.71073 Å Crystal system, space group orthorhombic, P 21 21 21 Unit cell dimensions a = 9.3055(16) Å, a = 90 ° b = 10.3538(15) Å, b = 90 ° c = 18.151(3) Å, g = 90 ° Volume 1748.8(5) Å3 Z, Calculated density 6, 1.164 g.cm-3 Absorption coefficient 0.066 mm-1 F(000) 648 Crystal size 0.800 x 0.580 x 0.450 mm Crystal color colourless Theta range for data collection 2.943 to 27.470 ° h_min, h_max -12, 12 k_min, k_max -13, 13 l_min, l_max -19, 23 Reflections collected / unique 10436 / 3996 [R(int) = 0.0274] Reflections [I>2sigma(I)] 3603 Completeness to theta_max 0.998 Absorption correction type multi-scan Max. and min. transmission 0.971 , 0.000 Refinement method Full-matrix least-squares on F^2 Data / restraints / parameters 3996 / 0 / 219 Goodness-of-fit 1.029 Final R indices [I>2sigma(I)] R1 = 0.0359, wR2 = 0.0870 R indices (all data) R1 = 0.0433, wR2 = 0.0924 Largest diff. peak and hole 0.190 and -0.176 e.Å-3

37

X-ray structure of diyne 13d

Table S4: Crystal data and structure refinement for 13b. Empirical formula C14H14 Formula weight 182.25 g/mol Temperature 150(2) K Wavelength 0.71073 Å Crystal system, space group triclinic, P -1 Unit cell dimensions a = 7.5855(9) Å, a = 90.902(5) ° b = 8.3989(11) Å, b = 91.564(5) ° c = 17.377(2) Å, g = 91.339(4) ° Volume 1106.2(2) Å3 Z, Calculated density 4, 1.094 g.cm-3 Absorption coefficient 0.061 mm-1 F(000) 392 Crystal size 0.490 x 0.410 x 0.270 mm Crystal color colourless Theta range for data collection 3.347 to 27.480 ° h_min, h_max -9, 9 k_min, k_max -10, 10 l_min, l_max -22, 22 Reflections collected / unique 21175 / 4978 [R(int) = 0.0363] Reflections [I>2sigma(I)] 4166 Completeness to theta_max 0.982 Absorption correction type multi-scan Max. and min. transmission 0.984 , 0.897 Refinement method Full-matrix least-squares on F^2 Data / restraints / parameters 4978 / 0 / 261 Goodness-of-fit 1.049 Final R indices [I>2sigma(I)] R1 = 0.0506, wR2 = 0.1353 R indices (all data) R1 = 0.0605, wR2 = 0.1420 Largest diff. peak and hole 0.307 and -0.265 e.Å-3

38


Table S5: Crystal data and structure refinement for 27. Empirical formula C34H36Si Formula weight 472.72 g/mol Temperature 150 K Wavelength 0.71073 Å Crystal system, space group triclinic, P -1 Unit cell dimensions a = 8.5423(11) Å, a = 76.313(5) ° b = 10.4335(14) Å, b = 77.803(5) ° c = 16.821(2) Å, g = 83.761(5) ° Volume 1421.0(3) Å3 Z, Calculated density 2, 1.105 g.cm-3 Absorption coefficient 0.102 mm-1 F(000) 508 Crystal size 0.420 x 0.280 x 0.090 mm Crystal color colourless Theta range for data collection 2.444 to 27.582 ° h_min, h_max -10, 11 k_min, k_max -13, 13 l_min, l_max -21, 21 Reflections collected / unique 26302 / 6444 [R(int) = 0.0702] Reflections [I>2sigma(I)] 5125 Completeness to theta_max 0.978 Absorption correction type multi-scan Max. and min. transmission 0.991 , 0.827 Refinement method Full-matrix least-squares on F^2 Data / restraints / parameters 6444 / 0 / 322 Goodness-of-fit 1.029 Final R indices [I>2sigma(I)] R1 = 0.0477, wR2 = 0.1191 R indices (all data) R1 = 0.0648, wR2 = 0.1301 Largest diff. peak and hole 0.453 and -0.368 e.Å-3

39


Table S6: Crystal data and structure refinement for 28.

Empirical formula C34H26 Formula weight 434.55 g/mol Temperature 150 K Wavelength 0.71073 Å Crystal system, space group triclinic, P -1 Unit cell dimensions a = 8.5611(8) Å, a = 94.453(3) °, b = 10.3957(10) Å, b = 104.612(3) °, c = 14.5334(13) Å, g = 98.456(3) ° Volume 1229.1(2) Å3 Z, Calculated density 2, 1.174 g.cm-3 Absorption coefficient 0.066 mm-1 F(000) 460 Crystal size 0.350 x 0.240 x 0.060 mm Crystal color colourless Theta range for data collection 2.914 to 27.482 ° h_min, h_max -11, 11 k_min, k_max -13, 13 l_min, l_max -17, 18 Reflections collected / unique 22961 / 5570 [R(int) = 0.0414] Reflections [I>2sigma(I)] 4477 Completeness to theta_max 0.987 Absorption correction type multi-scan Max. and min. transmission 0.996 , 0.874 Refinement method Full-matrix least-squares on F^2 Data / restraints / parameters 5570 / 0 / 310 Goodness-of-fit 0.034 Final R indices [I>2sigma(I)] R1 = 0.0479, wR2 = 0.1201 R indices (all data) R1 = 0.0628, wR2 = 0.1302 Largest diff. peak and hole 0.321 and -0.215 e.Å-3

40

References

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Cryst. 2006, 62, 505-509. [4] Karlen, S. D., Ortiz, R., Chapman, O. L., Garcia-Garibay, M. A., J. Am. Chem. Soc.

2005, 127, 6554-6555. [5] Fiandanese, V., Bottalico, D., Marchese, G., Punzi, A., Tetrahedron 2006, 62, 5126–

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11045–11057; b) Heppekausen, J.; Stade, R.; Kondoh, A.; Seidel, G.; Goddard, R.; Fürstner, A., Chem. Eur. J. 2012, 18, 10281–10299.

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Synthesis of Conjugated Triynes via Alkyne Metathesis