Tetrahedron Letters.. Vo1.32, No.5, pp 569-572.1991 printed m Great Britain

ca&4039/91 $3 cm+ Do Pergamon Ress plc

PALLADIUM-CATALYZED SYNTHESIS OF QUINOLINES FROM ALLYLIC ALCOHOLS AND o-IODOANILINE

Richard C. Larock* and Mann-Yan Kuo

Department of Chemistry, Iowa State University, Ames, Iowa 50011

Summary: The palladium-catalyzed coupling of allylic alcohols and o-iodoaniline provides a

convenient, one-step synthesis of quinolines.

Palladium-based methodology has provided valuable routes to a wide variety of heterocycles. 1

Though quinolines have been observed as unexpected products in the cyclization of N-allyhc anilines

to indoles, and indirect3 or miscellaneou&g routes to quinolines or their derivatives are known, the

only reasonably general routes ta quin~lines based Qn palladium chemistry are (,11 the cychzatlon of

N-(3-alkenyl)-o-iodoanilines (eq. 1),6 (2) the conjugate addition of appropriately functionalized

fl < cat. Pd(O)_ 2 (1)

a,/ l!I

arylmercurials to enones and subsequent cyclization (eq. 2),7 (3) the ortho palladation-olefination-

HgC1 H,C=CHCOR

NHR LizPdCL

HCl

(2)

cychzation of acetanilides (eq. 31s8 and (4) oh&nation Qf Q-iodaanilines by acrolein acetal (eq. 4).g We

wish to report a convenient, new, one-step synthesis of quinolines via palladium-catalyzed coupling

of o-iodoanilines and allylic alcohols.

569

570

I H2C=CHCH(OCH& H@+

NH2 cat. Pd(OAc)z

t

(4)

I% 53% 32%

The palladium-catalyzed coupling of o-iodoanilines and allylic alcohols according to Scheme 1

appeared to offer a promising new approach to quinolines heretofore unexplored. The palladlum-

catalyzed coupling of aryl halides and allylic alcohols is known to afford aryl ketones.9 Subsequent

intramolecular condensation to an imine and palladium-catalyzed dehydrogenation6 would be

expected to generate quinolines. Indeed, we wish to report that with the appropnate choice of

reaction conditions, this reaction affords in a single step quinolines in fair to good yields.

OH

Pdl H,C=CH&HR

NH2

IPd OH

CH,AH&HR -HPdI NHz

OH 0

1

HPdI e HI + Pd

The reaction of o-iodoaniline and 3-buten-2-01 was chosen as a model system and a wide variety

of reaction conditions were examined. l-2 equivalents of alkenol per aryl halide, 2.5-10% Pd catalyst

[Pd(OAc)z, PdC12, Pd(PPh&, Pd(dba)a, Pd(dppe)& presence or absence of 1 or 2 equivalents of hgand

per palladium [PPhs, (o-MeCsH&P, (P-MeZNCeH&P, Ph2PCH2CH2PPh2, P(OPhJ3, n-BuyPI,

presence or absence of 1 equivalent of n-BqNCl, 3 equivalents of various bases [NaOAc, KOAc,

NaHC03, KHCO3, Na2CO3, TMEDA, Et3NJ, various solvents [DMF, CH$N, DMSO, MeOH, HMPAI,

lOO-14O*C, 4-24 hours reaction time. The reaction proved surprisingly little affected by most variables

examined. The anticipated 2-methylquinoline product was formed under virtually all reaction

conditions, but it was almost always accompanied by substantial amounts of 2-methyl-1,2,3,4-

tetrahydroquinoline, presumably formed by reduction of the cyclic imine 1 (R = CH3). Typical ratios

of the desired quinoline to undesired tetrahydroquinoline were 1.53:l. This side product could only

be eliminated by running the reaction in HMPA.

The optimal conditions established for this qumoline synthesis proved to be 5 mol % PdC12, 5 11101

% PPh3, 3 equivalents NaHC03, 1.5 equivalents alkenol, 10 ml HMPA per mmol of o-iodoaniline, at

140C for 1 day under a nitrogen atmosphere. Using this procedure the quinolines reported in

571

Table I were prepared in fair to good yields.

TABLE I SYNTHESIS OF QUINOLINES

Entry Alkenol Quinoline % Isolated Yield

1

2

OH H,C=CHCHCH,

YH H,C = CHCHCsHS

CH3

H2C=CCH20H

76H5

H,C =CCH,OH

5 CH,CH=CHCH,OH

C6H5

62

50

52

li,23a

40

Reaction run for four days.

The reaction is reasonably versatile. A variety of allyhc alcohols can be employed, although ally1

alcohol itself gave only a mixture of products from which quinohne could not be easily isolated As

expected from previous work on the addition of organopalladium compounds to alkcncs, the more

substituted the carbon-carbon double bond, the lower the yield. Nevertheless, even crotyl alcohol

(entry 5) gives a reasonable yield. Primary and secondary alcohols have been employed with

approximately equal success. However, when the carbon-carbon double bond is placed in

conjugation with an aromatic ring, poor results are obtained (entry 4). Substantial amounts of the

starting alkenol are still present at the end of this reaction.

In conclusion, a convenient new route to the quinoline ring system has been developed via the

palladium-catalyzed coupling of o-iodoaniline and allylic alcohols. The starting materials ale

readily available. The reactions are generally quite clean, affording a single predictable product m

reasonable isolated yield. The reaction accommodates a variety of substitution patterns and previous

experience suggests that it should accommodate a wide variety of functional groups I0

Acknowledgment. The financial support of this research by the National Institutes of Health

(GM 40036) and generous loans of palladium reagents by Kawaken Fine Chemicals, Ltd. and

Johnson Matthey, Inc. are deeply appreciated.

572

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(Received in USA 15 October 1990)