This article was published as part of the

2009 Metal–organic frameworks issueReviewing the latest developments across the interdisciplinary area of

metal–organic frameworks from an academic and industrial perspective Guest Editors Jeffrey Long and Omar Yaghi

Please take a look at the issue 5 table of contents to access the other reviews.

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Enantioselective catalysis with homochiral metal–organic frameworksw

Liqing Ma, Carter Abney and Wenbin Lin*

Received 24th October 2008

First published as an Advance Article on the web 23rd February 2009

DOI: 10.1039/b807083k

This tutorial review presents recent developments of homochiral metal–organic frameworks

(MOFs) in enantioselective catalysis. Following a brief introduction of the basic concepts and

potential virtues of MOFs in catalysis, we summarize three distinct strategies that have been

utilized to synthesize homochiral MOFs. Framework stability and accessibility of the open

channels to reagents are then addressed. We finally survey recent successful examples of

catalytically active homochiral MOFs based on three approaches, namely, homochiral MOFs

with achiral catalytic sites, incorporation of asymmetric catalysts directly into the framework, and

post-synthetic modification of homochiral MOFs. Although still in their infancy, homochiral

MOFs have clearly demonstrated their utility in heterogeneous asymmetric catalysis, and a bright

future is foreseen for the development of practically useful homochiral MOFs in the production

of optically pure organic molecules.

Introduction

Metal–organic frameworks (MOFs), also known as coordina-

tion polymers, are hybrid solids with infinite network structures

built from organic bridging ligands and inorganic connecting

points.1–5 MOFs can be constructed from designer building

blocks to impart unique properties for a wide range of potential

applications including nonlinear optics,6 gas storage,7–10

sensing,11 and catalysis.12–15 One of the most extraordinary

features of MOFs is their ability to possess unprecedentedly

high porosity. Depending on the size of ligands and inorganic

connecting points and network connectivity, the porosity of

MOFs can be readily tuned to afford open channels and pores

with dimensions of several angstroms to several nanometres.

The ability to incorporate functional groups into porous

MOFs makes them excellent candidates as heterogeneous

catalysts. The well-defined pores and channels in MOFs have

the potential to endow them with the size- and shape-selective

catalysis that is the hallmark of zeolites. The diversity of

zeolites, however, is rather limited due to the use of exclusively

SiO4/AlO4 tetrahedral building units. The resulting 3D frame-

works of zeolites are microporous with channels/cavities of up

to 1.0 nm, and as a result, the catalytic applications of zeolites

are restricted to relatively small organic molecules (typically

no larger than xylenes). In contrast, MOFs can be built from

an infinite number of building blocks to allow for a systematic

fine-tuning of their properties. Furthermore, the mild synthetic

conditions typically employed for MOF synthesis allow direct

incorporation of a variety of delicate functionalities into the

framework structures. For example, either enantiopure

chiral ligands or their metal complexes can be incorporated

directly into the frameworks of MOFs to lead to efficient

asymmetric catalysts. Such a process would not be possible

with zeolites or other microporous crystalline oxide-based

materials because of the harsh conditions typically used for

their synthesis (e.g., calcination at high temperatures to

remove organic templates).

Department of Chemistry, CB#3290, University of North Carolina,Chapel Hill, NC, 27599, USA. E-mail: wlin@unc.edu;Fax: +1-919-962-2388; Tel: +1-919-962-6320w Part of the metal–organic frameworks themed issue.

Liqing Ma

Liqing Ma obtained his PhDdegree from Case WesternReserve University in 2006under the supervision ofProf. John D. Protasiewicz.Currently he is a PostdoctoralAssociate with Prof. WenbinLin at the University of NorthCarolina at Chapel Hill. Hiscurrent research focuses on de-veloping porous metal–organicframeworks for gas storage,chiral separation, and hetero-geneous catalysis.

Carter W. Abney

Carter W. Abney obtained hisBS degree from the Universityof Wisconsin at Madison in2007. He is currently a PhDstudent at the University ofNorth Carolina at Chapel Hillunder the guidance of Prof.Wenbin Lin. His researchemphasis is on the developmentof novel homochiral metal–organic frameworks and theircatalytic applications.

1248 | Chem. Soc. Rev., 2009, 38, 1248–1256 This journal is �c The Royal Society of Chemistry 2009

TUTORIAL REVIEW www.rsc.org/csr | Chemical Society Reviews

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In spite of the great potential for MOFs in heterogeneous

catalysis, very few of them have been explored for catalytic

applications. This is in part due to the relative thermal and

hydrolytic instability of MOFs as compared to zeolites.

Furthermore, it remains a great challenge to engineer very

strong Lewis acid or Brønsted acid sites in MOFs. These two

limitations make it difficult for MOFs to find applications in

many of the processes that are currently catalyzed by zeolites

(such as hydrocracking of crude oil).

Two very different strategies have been utilized to synthesize

catalytically active MOFs. In the first approach, the

metal-connecting points with unsaturated coordination

environments are utilized as catalytically active sites. The

metal-connecting points in MOFs typically have coordinated

water or other solvent molecules that can be readily removed

without distorting the framework structures. Such accessible,

coordinatively unsaturated metal centers can be used to catalyze

organic reactions (Scheme 1). In the second approach, catalytic

sites are incorporated directly into the bridging ligands used to

construct MOFs (Scheme 2). Although more synthetically

demanding, the second approach is much more versatile and

allows for the incorporation of a wide variety of catalysts.

Compared to the limited number of MOFs that have been

used as achiral catalysts, even fewer examples have been

reported for application in asymmetric catalysis, despite the

great importance of heterogeneous asymmetric catalysis in the

production of enantiomerically pure products. The scarcity of

MOF-based heterogeneous asymmetric catalysts is directly

related to the difficulty of designing porous MOFs with open

channels that are several nanometres in dimension. Such large

open channels are essential for asymmetric catalytic reactions

because of the need to transport organic substrates and

products that are typically quite sizeable.

In the present review, we briefly introduce the basic concepts

of catalysis with MOFs and describe the general strategies for

the synthesis of homochiral MOFs. We then survey recent

examples of homochiral MOFs that have been examined for

heterogeneous asymmetric catalysis.

Strategies for homochiral MOF synthesis

Homochiral MOFs with built-in catalytic sites are necessary for

enantioselective reactions, and thus far three distinct strategies

have been used for their construction. In the first approach,

homochiral MOFs are prepared from totally achiral components

via self-resolution during crystal growth. Such a strategy would

offer the greatest advantage as it does not use chiral components

which often require laborious synthesis and are typically

expensive. Although numerous claims of such self-resolution of

homochiral MOFs have been made, almost all of these MOFs

are in fact racemic because their bulk samples contain both

enantiomorphs (opposite handedness) of MOFs. Aoyama and

coworkers reported the first example of obtaining a homochiral

MOF Cd(apd)(NO3)2�H2O�EtOH, 1, based on achiral Cd2+

centers and 5-(9-anthracenyl)pyrimidine (apd) bridging ligand.16

1 crystallizes in the chiral space group P21, with chirality arising

from a pyrimidine-Cd2+ helical array (Fig. 1). Crystals of 1 were

observed to grow radially from the first appearing nucleus,

suggesting the possibility of seeding the growth of homochiral

1 in the bulk. By using solid-state circular dichroism spectro-

scopy, they convincingly demonstrated the seed-induced

synthesis of homochiral 1 from totally achiral components.

Zheng and coworkers recently demonstrated the synthesis

of homochiral MOFs from totally achiral components by

Scheme 1 Coordinatively unsaturated metal connecting points as

active catalytic sites.

Scheme 2 Incorporation of active catalytic sites into the bridging

ligands of MOFs.

Fig. 1 Structure of 1 showing two hydrogen-bonded helices.Wenbin Lin

Wenbin Lin is a professor ofchemistry and pharmacy at theUniversity of North Carolina atChapel Hill. His researchfocuses on designing novelmolecular and supramolecularsystems and hybrid nano-materials for applications inchemical and life sciences. Hehas published B150 papers inseveral research areas.

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chemically manipulating the statistical fluctuation of enantio-

meric pair formation.17 The kinetics of [{Cu(succinate)-

(4,40-bipyridine)}n]�(4H2O)n (2) crystallization were retarded

when ammonia was added to the mixture as a competing

ligand, resulting in the formation of fewer parent crystals.

Careful tuning of ammonia concentrations and solvent

evaporation rates led to the growth of a single cluster of

homochiral 2. This elegant chiral symmetry breaking strategy

obviates the use of a seed crystal, but the handedness of the

MOF crystals cannot be known a priori.

In the second approach, bulk homochiral MOFs are

synthesized from achiral metal connecting points and bridging

ligands under chiral influence. Rosseinsky and coworkers

utilized enantiomerically pure 1,2-propanediol as a chiral

template (co-ligand) to synthesize homochiral MOFs

from 1,3,5-benzenetricarboxylate (btc) and M(NO3)2�6H2O

(M = Ni, Co).18,19 Enantiopure 1,2-propanediol chelates to

the metal centre, allowing the stereochemistry of the metal

to control the absolute helicity of the growing polymeric

structure and to determine the nature of interpenetration.

Morris and coworkers recently utilized ionic liquids with chiral

anions to induce spontaneous crystallization of homochiral

MOFs of the same enantiomorph.20 Using the chiral ionic

liquid 1-butyl-3-methylimidazolium L-aspartate (BMIm-L-asp)

as the reaction medium, homochiral (BMIm)2[Ni(btc-H)2(H2O)2]

(3) was obtained (Fig. 2). Although containing neither chiral

ligands nor chiral anions, 3 crystallizes in the chiral space

group P41212. Analysis of 10 randomly selected crystals of 3

by single-crystal X-ray determination verified the enantio-

morphic purity. Chiral induction was further supported by

the fact that substitution of L-aspartate with D-aspartate

yielded crystals of 3 with the opposite chirality and that

removal of chiral anions in the ionic liquid resulted in an

achiral MOF (BMIm)2[Ni3(btc-H)4(H2O)2].

More recently, Bu and coworkers further advanced the

concept of chiral influence and successfully used sub-

stoichiometric amounts of a chiral spectator to amplify the

chiral induction of homochiral MOFs from achiral bulking

blocks.21 Utilizing small amounts of the alkaloids

(�)-cinchonidine or (+)-cinchonine, enantomorphically pure,

homochiral MOFs such as (Me2NH2)[In(thb)2]�xDMF (4)

were grown from achiral precursors (H2thb refers to thiophenen-

2,5-dicarboxylic acid). As expected, crystals of opposite

chirality were obtained when they were grown in the presence

of (�)-cinchonidine or (+)-cinchonine. The resulting crystals

were found to be racemic twins when no chiral alkaloid was used.

The third approach to homochiral MOF construction is to

use readily available chiral linker ligands as the building

blocks. This approach not only provides the most reliable

means for homochiral MOF synthesis, but also allows the

synthetic elaboration of the chiral bridging ligands to impart

desirable functionalities for asymmetric catalysis. Indeed, all

of the homochiral MOFs examined for asymmetric catalysis so

far were prepared via this third strategy. Any of the chiral

auxiliaries used for homogeneous asymmetric catalysis can, in

principle, be elaborated to contain functionally orthogonal

groups to bridge metal centres and form homochiral MOFs.

For example, Lin et al. have extensively functionalized

1,10-binaphthyl-derived chiral auxiliaries, such as 1,10-bi-

naphthalene-2,20-diol (BINOL) and, 2,20-bis(diphenylphosphino)-

1,10-binaphthyl (BINAP), with exo-bidentate or exo-multidentate

bridging ligands to construct a variety of homochiral

MOFs.22–24 The 1,10-binaphthyl framework is of particular

interest because of the ability to selectively functionalize

the different positions (e.g. 2,20-, 3,30-, 4,40-, 5,50-, 6,60-,

and 7,70-positions as well as several combinations of them)

with a variety of groups such as pyridyl, carboxyl, and

phosphonic acid (Scheme 3). Furthermore, these functional

groups can be installed on the 1,10-binaphthyl framework via

different linkers to afford chiral bridging ligands of the same

geometry but varied lengths. Such ligand families are of great

importance in constructing homochiral MOFs with tunable

porosity and pore and channel sizes.

Framework stability and reagent-accessible channels

For a homochiral MOF to function as an effective hetero-

geneous asymmetric catalyst, it needs to maintain its frame-

work structure during the catalytic reaction, as well as sustain

the open channels to allow rapid transport of the reagents and

the products. Chiral MOFs with large open channels (typically

larger than 1.5 nm) are desired due to the large size of

prochiral substrates and the resulting chiral products.

Unfortunately, MOFs with large open channels tend to

undergo significant framework distortion upon the removal

of solvent molecules, affording materials that exhibit veryFig. 2 Perspective view of 3 along the a axis showing the two helices

with the same handedness running through both a and b axes.

Scheme 3 Examples of BINOL-derives chiral ligands used by the Lin

group.

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different powder X-ray diffraction (PXRD) patterns than

those of the pristine solids. These MOFs also typically exhibit

lower surface areas than those calculated from single crystal

structure data. It is thus important to demonstrate the frame-

work stability of homochiral MOFs during the catalytic

reactions and to prove the accessibility of their open channels

to large organic molecules.

In order to demonstrate framework stability of homochiral

MOFs, Wu and Lin synthesized a 1D homochiral MOF

[Cd(L1)2(ClO4)2]�11EtOH�6H2O, 5, built from the elongated

di-pyridyl ligand L1 and Cd(ClO4)2.25 The pristine crystals lost

crystallinity upon removal of the included solvent molecules as

judged by PXRD. However, the crystallinity was readily

restored when the amorphous material was exposed to a

solvent vapour. More importantly, the homochiral MOF

remained crystalline and underwent a single-crystal-to-single-

crystal transformation during the solvent exchange process

(Fig. 3). These results indicate that the framework distortion

does not negatively impact the accessibility of solvent mole-

cules to the open channels and that the homochiral framework

structure should be maintained under typical heterogeneous

asymmetric catalytic conditions where a solvent is involved.

More recently, Lin and co-workers reported homochiral

MOFs based on a BINOL-derived tetra-carboxylate bridging

ligand L2.26 The resulting 3D MOF [Cu2(L2)(H2O)2]�(DEF)12�

(H2O)16, 6, possesses large channels of 3.2 nm running through

the b axis (Fig. 4), and represents the first example of a

mesoporous homochiral MOF. Interestingly, this system

exhibits catenation isomerism that is not only controlled by

the chirality of the bridging ligand but also influenced by the

solvent used to grow the MOF crystals. When the crystals

were grown in dimethylformamide (DMF), the enantiopure

ligand L2 gave a noninterpenetrating structure, while the

racemic L2 yielded a 2-fold interpenetrated MOF 7 (Fig. 4).

However, both enantiopure and racemic L2 yielded

non-interpenetrating structures when the crystals were grown

from diethylformamide (DEF). The non-interpenetrating

framework 6 has a remarkable solvent accessible void space

of B85% as calculated by PLATON, whereas the 2-fold

interpenetrated framework 7 has a smaller void space of

B70% and possess smaller open channels of 1.4 � 0.7 nm.

As a result of the very open structures, the frameworks of both

6 and 7 severely distorted when the solvent molecules were

removed and exhibited surface areas much smaller than those

calculated from single crystal data. In spite of such evacuation-

induced framework distortion, 6 readily took up 103 wt%

(dye/framework) of the nano-sized dye molecule Brilliant Blue

R-250, with dimensions of B1.8 � 2.2 nm. In contrast, 7 took

up only 10.6 wt% of Brilliant Blue R-250 under the same

conditions, presumably via surface adsorption. The resulting

dye-incorporated solids exhibited the same PXRD patterns as

pristine 6 and 7. These results conclusively demonstrate the

maintenance of open channels in these frameworks and the

accessibility of the open channels to nano-sized molecules in

solution.

Recent examples of enantioselective catalysis with

homochiral MOFs

Several strategies have been used to construct catalytically

active homochiral MOFs. Earlier attempts focused on

examining the activities of achiral catalytic sties that were

incorporated into the homochiral MOFs.13,27 Enantio-

selectivities of such systems arise from the remote influence

by chiral environments of the open channels, and to date,

disappointingly low ee’s were obtained with this approach.

Later efforts were directed toward designing homochiral

Fig. 3 Schematic illustration of reversible single crystal to single

crystal transformations of 5.

Fig. 4 (a) A view of the [Cu2(O2CR)4] paddle-wheels in 6 and their

connectivity with R-L2. (b) Space filling model of [R-L2Cu2] (6) viewed

down the b axis, showing open channels of 3.2 nm at the greatest

point. (c) The largest channels of 3.2 nm can be described as helices

running through both a and b axes. (d) Two-fold interpenetrating

structures of [rac-L2Cu2] (7).

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MOFs with bridging ligands that contain chiral functional

groups exploitable for asymmetric catalysis based on two

distinct approaches. In the precatalyst approach, bridging

ligands containing asymmetric catalytic sites are linked with

metal-connecting points to generate homochiral MOFs. In an

alternative and complementary post-synthetic modification

approach, homochiral MOFs are constructed with chiral

bridging ligands that contain secondary and orthogonal

functionalities. The secondary functional groups are then

converted into catalytic sites via post-synthetic modification.

Although the precatalyst approach provides a versatile

method for synthesizing a wide range of catalytically active

homochiral MOFs, it is not compatible with some of the less

stable Lewis acid and late transition metal catalysts. The

post-synthetic modification approach overcomes this limita-

tion and expands the range of heterogeneous asymmetric

catalysts based on homochiral MOFs.

Achiral catalytic sites within homochiral MOFs

Kim et al. reported the first example of asymmetric catalysis

with a homochiral MOF based on an enantiopure

tartaric acid-derived bridging ligand L4, and the Zn3(m3-O)-

(carboxylate)6 secondary building unit (SBU). Homochiral

[Zn3(m3-O)(L4-H)6]�2H3O�12H2O (8) was synthesized under

solvothermal conditions (Scheme 4).27 Three zinc ions are held

together by six carboxylate groups and a m3-oxygen to form

the enantiopure trinuclear SBU (Fig. 5). Each of the SBUs

possesses six pyridyl groups, with two of them protonated and

three of them involved in coordination with zinc ions. The

Zn3(m3-O)(carboxylate)6 SBUs are linked by the L4 ligands to

generate 2D layers with a hexagonal topology. The resulting

MOF has large (B13.4 A) chiral 1D channels along the c axis

and an estimated void space of B47%. The remaining

pyridine is exposed in the channels of 8 and endows the

MOF with its catalytic properties.

Compound 8 catalyzed the transesterification between an

aromatic ester (A) and ethanol to afford ethyl acetate in 77%

yield after reacting in carbon tetrachloride for 55 h (Scheme 5).

Under similar conditions, a very modest enantiomeric excess

(ee) of B8% was observed when 8 was used to catalyze the

transesterification of A with racemic 1-phenyl-2-propanol.

Lin et al. prepared a series of homochiral MOFs

[Ln(L3-H2)(L3-H3)(H2O)4]�xH2O (9) based on lanthanide

phosphonate and examined their activities as Lewis acid

catalysts by taking advantage of the lanthanide metal-

connecting points (Fig. 6).28 Unfortunately, negligible ee’s

were observed in several Lewis acid catalyzed reactions

including cyanosilylation of aldehydes and ring opening of

meso-carboxylic anhydrides. These results illustrate the challenge

in designing highly enantioselective MOF catalysts via remote

influence by chiral environments of the open channels.

Incorporation of asymmetric catalysts directly into the

framework

A more reliable route to designing homochiral MOFs with

asymmetric catalytic activity is to utilize bridging ligands that

contain ready-to-use catalysts. As chiral metal complexes have

been widely used for enantioselective organic transformations

under homogeneous conditions, their incorporation into

bridging ligands can directly impart asymmetric catalytic

activities to the resulting MOFs.

Lin and coworkers have designed BINAP based homochiral

bridging ligands (L5 and L6) with ruthenium complexes

incorporated in the scaffold. Such diphosphoric acid substi-

tuted ligands were reacted with zirconium tetra-tert-butyloxide

to yield chiral porous hybrid solids 10 and 11 (Scheme 6).23

With the imbedded Ru(BINAP)(diamine)Cl2 precatalysts, 10

and 11 showed excellent enantioselectivity for the asymmetric

hydrogenation of aromatic ketones (up to 99.2% ee). These

catalysts were readily recycled by centrifugation, and could be

reused up to 10 times without significant loss of activity or

enantioselectivity. Analogous zirconium phosphonates con-

taining Ru(BINAP)(DMF)2Cl2 moieties were also prepared

and used for asymmetric hydrogenation of b-keto esters.29

Scheme 4 Synthesis of homochiral MOF 8.

Fig. 5 1D equilateral triangular shape channel along the c axis of 8,

with a size of 13.4 A (left); coordination environment or metal centres

of 8, showing the catalytic centre and the chiral pocket (right).

Scheme 5 Transesterification reactions catalyzed by 8.

Fig. 6 Perspective view of 9 along the a axis, showing lamellar

structure. Different colours illustrate different lamellae.

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These zirconium phosphonate-based solids are amorphous,

however, and difficult to characterize in molecular details.

Hupp and coworkers reported a homochiral MOF

constructed from the chiral (salen) Mn ligand L7, biphenyl-

4,40-dicarboxylic acid (H2bpdc), and Zn2+ ions (Scheme 7).

The framework [Zn2(bpdc)2L7]�10DMF�8H2O (12) was

obtained under solvothermal conditions, showing a twofold

interpenetrating 3D network with 57% solvent accessible

volume (Fig. 7).15 The channels in the a and c directions

possess dimensions of 6.2 � 6.2 A and 6.2 � 15.7 A, respec-

tively. Due to the diagonal displacement of the network, all

MnIII sites are accessible to the channels (Fig. 8).

Compound 12 was examined for asymmetric olefin

epoxidation reactions and effectively catalyzed the epoxidation

of 2,2-dimethyl-2H-chromene to result in the desired product

in 71% yield and 82% ee (Scheme 8). 12 has a higher activity

than the homogeneous counterpart, albeit with slightly lower

enantioselectivity. Unlike related homogeneous epoxidation

catalysts, which are highly active for only a few minutes, 12

maintained its activity throughout a three hour reaction

period. Additionally, 12 was recycled and reused three times,

displaying only a slight decrease in activity and no loss in

enantioselectivity.

Based on an approach developed by the Lin group, Tanaka

and coworkers used 5,50-dicarboxy-substituted BINOL as a

bridging ligand (L8) to react with copper nitrate under

solvothermal conditions (Scheme 9).30 The resulting 2D

infinite framework [Cu2(L8)2(H2O)2]�MeOH�H2O (13) con-

tains copper paddle-wheels as SBUs and are stacked along

the b axis with an interlayer Cu–Cu distance of 15.6 A (Fig. 8).

The water molecules terminating the copper paddle-wheels

were removed upon heating, allowing the exposed copper

centres to function as Lewis acid catalytic reaction centres.

To test the catalytic activity of framework 8, the asymmetric

ring-opening of epoxides with amines was examined

(Scheme 10). Following 48 h of reacting at 25 1C in toluene,

a maximum 54% yield with 45% enantiomeric excess was

obtained. The catalyst was recovered by filtration and recycled

without detrimental affect to the reactivity and enantio-

selectivity. Interestingly, enantioselectivity and reactivity both

Scheme 6 Asymmetric hydrogenation of aromatic ketones catalyzed

by homochiral hybrid solids 10 and 11.

Scheme 7 Chiral bridging ligand L7 with (salen) Mn complex and the

achiral bridging ligand H2bpdc.

Fig. 7 Schematic representation of open channels and catalytic active

sites within the two-fold interpenetrating framework of 12.

Fig. 8 Stacking patterns of a 2D grid of 13 as viewed along the c axis.

Scheme 8 Asymmetric epoxidation catalyzed by 12.

Scheme 9 Schematic representation of the synthesis of 13 and the

connectivity of L8 and the copper paddle wheels.

Scheme 10 Asymmetric ring-opening reaction of epoxide with amine

catalyzed by 13.

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improved under solvent-free conditions. Control experiments

indicated that (S)-BINOL itself is not catalytically active. To

date, the mechanism of this catalytic reaction remains unclear.

Post-synthetic modification of homochiral MOFs

Lin and co-workers pioneered the post-synthetic route to

catalytically active homochiral MOFs by utilizing orthogonal

functionalities within the backbones of BINOL-derived

bridging ligands. For example, 3D homochiral MOF

[Cd3(L9)3Cl6]�4DMF�6MeOH�3H2O (14) was synthesized via

slow vapour diffusion of diethyl ether into a mixture of L9 and

CdCl2 in DMF/MeOH.24 Through the linkage of 1D zigzag

[Cd(m-Cl)2]n SBUs with the L9 ligands via pyridine coordina-

tion, the 3D framework showed the largest channel opening of

1.6 � 1.8 nm running along the a axis (Scheme 11 and Fig. 9).

The permanent porosity of 14 was characterized by CO2

adsorption experiments that showed a surface area of

601 m2 g�1. Despite the use of such an elongated ligand, frame-

work catenation was prevented due to the 1D zigzag Cd chain.

Further analysis of the framework 14 reveals that two-thirds

of the orthogonal hydroxyl groups are inaccessible due to tight

pairing of L9 ligands by hydrogen-bonding and p� � �p stacking

interactions, but the remaining third are oriented into the

channels and readily react with Ti(OiPr)4 to form a chiral

catalytic species and thus functionalize the MOF (Fig. 10). The

resulting Ti-BINOLate species are capable of catalyzing the

diethylzinc addition to aldehydes with high ee’s up to 93%

(Table 1), which is comparable to the homogeneous analogue

(94%). The absence of catalytic activity in the supernatant of

the 14 and Ti(OiPr)4 mixture illustrated the heterogeneous

nature of this porous solid. To confirm that the aldehydes are

accessing the active Ti sites located within the interior of the

framework, a series of aldehydes with sizes from 0.8 nm to

2.0 nm were tested. The data showed that larger aldehydes

gave lower conversions, which further demonstrates that

catalytic conversion happened inside the crystal channels,

and verifies the heterogeneous nature of 14.

It is well-established that different anions used in the crystal

growth may direct the growth of different MOF structures.

For example, the reaction of CdCl2 with L9 afforded

[Cd(m-Cl)2]n SBUs resulting in the formation of a MOF with

large open channels. In contrast, the MOFs formed by

Cd(NO3)2 and Cd(ClO4)2 with L9 adopted two different

Scheme 11 Schematic representation of the synthesis of 14, and its

3D network showing zigzag chains of [Cd(m-Cl)2]n along the a axis.

Fig. 9 (a) Space-filling model of 14 as viewed down the a axis,

showing the large 1D chiral channels (1.6 � 1.8 nm). (b) Schematic

representation of the active (BINOLate)Ti(OiPr)2 catalytic sites in the

open channels of 14.

Fig. 10 (a) The 2D square grid in 15. (b) Schematic representation of

the 3D framework of 15. (c) Schematic representation of the inter-

penetration of mutually perpendicular 2D grids in 16. (d) Schematic

representation of steric congestion around the chiral dihydroxyl group

of L9 (orange sphere) arising from the interpenetration of mutually

perpendicular 2D grids in 16.

Table 1 Ti(IV)-catalyzed ZnEt2 additions to aromatic aldehydes

Ar

BINOL/Ti(OiPr)4 14�Ti

Conv.(%) ee(%) Conv.(%) ee(%)

1-Naph 499 94 499 93Ph 499 88 499 834-Cl-Ph 499 86 499 803-Br-Ph 499 84 499 8040-G0OPh 499 80 499 8840-G1

0OPh 499 75 73 7740-G1OPh 499 78 63 8140-G2

0OPh 95 67 0 —

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homochiral structures, [Cd3(L9)4(NO3)6]�7MeOH�5H2O (15)

and [Cd(L9)5(ClO4)2]�DMF�4MeOH�3H2O (16), respectively,12

with both networks containing 2D grids as shown at Fig. 10a.

In 15 the grids are stacked in layers, interconnected by 1D

polymeric chains (green zigzag line at Fig. 10b), and possess

large channels with dimensions of 13.5 � 13.5 A along the

c axis. However, framework 16 was constructed solely by 2D

grids and displays a 2-fold interpenetrating pattern (Fig. 10c)

to result in 12 � 15 A 1D channels.

When activated by Ti(OiPr)4, framework 15 showed very

good enantioselectivity (up to 90% ee) in the diethylzinc

addition to aromatic aldehydes. Surprisingly, framework 16

showed no activity at all under the same reaction conditions.

Further examination revealed the interpenetration pattern

adopted by 16 brought dihydroxyl groups from one 2D

grid within close proximity of the the Cd(py)2(H2O)2 moiety

in the other 2D grid (Fig. 11d). The Cd(py)2(H2O)2moiety sterically prohibits the Ti(OiPr)4 from reacting with

the dihydroxyl groups and prevents formation of the active

Ti-BINOLate species. It is this subtle structural difference that

leads to completely different catalytic reactivity of the two

frameworks.

Rosseinsky and coworkers recently reported a microporous

MOF that can afford Brønsted acid sites after post-synthetic

modification.31,32 The open framework [Cu(L-asp)2(bipy)]�2HCl�H2O (17) was obtained by a solvothermal reaction of

Cu(L-asp)�3H2O with 4,40-bipyridine (bipy) in H2O and

MeOH, followed by protonation with HCl. As evidenced by

powder X-ray diffraction, 17 bears a very similar structure to

its Ni counterpart framework, which contains 1D channels of

size 4.3 � 3.2 A running through the b axis (Fig. 11). When a

longer ligand 1,2-bis(4-pyridyl)-ethane (bpe) was used, frame-

work 17b with larger 1D channels of 8.6 � 3.2 A was obtained.

The resulting Brønsted acid sites were used to catalyze the

methanolysis of cis-2,3-epoxybutane (Scheme 12). Both 17 and

17b showed some enantioselectivity, however, in all test reac-

tions moderate yields (32–65%) and very low ee’s (up to 17%)

were obtained. Nevertheless, their heterogeneous nature was

evidenced by the inactive filtered supernatant. No conversion

was observed for attempted methanolysis of the bulkier

epoxide (2,3-epoxypropyl)-benzene, suggesting catalysis does

occur mostly in the channels and pores rather than on the

external surfaces.

Conclusions

This review summarized the developments of homochiral

MOFs for applications in heterogeneous asymmetric catalysis.

The various synthetic techniques used in homochiral MOF

formation were discussed and their ability to maintain frame-

work structure during solvent exchange and to take up

nanosized dye molecules was analyzed. Finally, recent exam-

ples of MOFs used in asymmetric catalysis were reviewed.

Although inferior to zeolites in thermal or hydrolytic stability,

MOFs possess extensive tunability, highly regular catalytic

sites, and homochirality and thus represent a unique oppor-

tunity to design MOF-based heterogeneous asymmetric

catalysts. Homochiral MOFs have a bright future in the

asymmetric catalytic synthesis of important optically pure

organic molecules.

Acknowledgements

We thank NSF for financial support.

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