The conjugate addition reaction of carbon nucleophiles to electron-deficient olefins is one of the most reliable methods for selective C-C bond formation. However, the conjugate addition to the vinylogous electron-deficient dienes has been much less developed, as there is considerably more difficulty in controlling the regioselectivity of the addition to these extended conjugate systems due to the presence of three electrophilic sites, as well as the stereoselectivity. Although still underdeveloped, new approaches to tackle these challenges are beginning to emerge. Both transition-metal-catalyzed and organocatalytic approaches are currently being developed to cope with the main selectivity issues of this type of process: regioselectivity (1,2-, 1,4-, and 1,6-addition) and stereoselectivity (asymmetric formation of the new C-C bonds). In this tutorial review, we have surveyed representative examples to get an overview of the recent advances obtained in the scope of the conjugate addition reaction of carbon nucleophiles to electron-deficient dienes.

[reaction: see text] The stereoselective Rh(I)-catalyzed conjugate addition reaction of aryl and alkenylboronic acids to unprotected 2-phenyl-4-hydroxycyclopentenone is presented. The free OH group on the substrate is responsible for the stereochemistry, which is cis for arylboronic derivatives. In the case of the alkenylboronic compounds, the stereochemistry can be tuned to either a cis (bases as additives) or trans addition (CsF as additive) without the need of protecting groups.

Gramine-MeI salts were useful starting materials for the synthesis of 3-benzyl- and 3-allylindoles by the 1,4-addition of boronic acids to the C=C-C=N linkages generated in situ under Rh(I)-catalysis. On the other hand, under Ir(I) catalysis, the reaction of gramines with indoles was used to produce nonsymmetrical diindolylmethanes. [reaction: see text]

Cyclopentane derivatives Q 0030 Stereoselectivity Control in the Rh(I)-Catalyzed Conjugate Additions of Aryl and Alkenylboronic Acids to Unprotected Hydroxycyclopentenones. -The stereochemistry concerning the reaction of alkenylboronic acids (IV) with pentenone (I) can be tuned by the appropriate additive without the need of protecting the free hydroxyl group. -(DE LA HERRAN, G.; MBA, M.; MURCIA, M. C.; PLUMET, J.; CSAKY*,

Catalysts. -Gramines are used under optimized conditions as substrates for in situ generation of C=C-C=N conjugate systems which further react with indole (II) or boronic acids to give the products shown in the scheme. -(DE LA HERRAN, G.; SEGURA, A.; CSAKY*, A. G.; Org. Lett. 9 (2007) 6, 961-964; Dep. Quim. Org., Fac. Quim., Univ. Complutense, E-28040 Madrid, Spain; Eng.) -R. Steudel 31-089

Review: 60 refs.

The stereoselective conjugate addition reaction of organolithium reagents to unprotected 4-hydroxycyclopentenones is reported. The OH group on the substrate is transformed into the corresponding magnesium alkoxide, which has been used to control the regioselectivity of the organolithium addition. Following this procedure, the conjugate addition reaction was obtained instead of the products of direct addition to the carbonyl group usually found in other organolithium additions to similar starting materials. Additionally, the OH group controls the cisstereochemistry of the final products. Both aspects, regio-and stereoselectivity, can be understood by means of a chelation-controlled addition.

We report a concise synthesis of the enantiomerically pure 1,2-trans-1,5-cis-methyl esters of rosaprostol, a prostaglandin derivative used for the treatment of gastric and duodenal ulcers, using as key step the chemo-and stereoselective Michael addition of a Grignard reagent to an unprotected hydroxycyclopentenone.