For the first time, an excellent enantioselectivity has been obtained in the conjugate addition of hard organometallic reagents to alpha,beta-unsaturated lactams bearing appropriate protecting-activating groups on the nitrogen.

An unprecedented regioselective and anti stereoselective asymmetric ring opening of 1,3-cyclopentadiene-heterodienophile cycloadducts, including also 2,3-diazabicyclo[2.2.1]heptenes, with hard alkylmetals and copper-phosphoramidite catalysts, is reported. The induced ring opening, in conjunction with C-C bond formation, gives a catalytic and practical access to new heterofunctionalized cyclopentenes in an enantioenriched form (up to 86% ee). [reaction: see text]

A novel regiodivergent kinetic resolution of a series of allylic epoxides with alkylzinc reagents is described. Results demonstrate the potential of chiral copper-phosphoramidite catalysts for enantiomer differentiation of allylic epoxides, allowing a chiral catalyst-stereoregulated synthesis of cyclic allylic and homoallylic alcohols with high optical purities.

A new and practical way to introduce an alkyl fragment in the b-position of aliphatic carboxylic acid derivatives with high enantioselectivities by the use of a commercially available chiral ligand is reported. N-Acylpyrrolidinones, as simple derivatives of an a,b-unsaturated carboxylic acid, were found to be the substrates of choice featuring good reactivity and high enantioselectivities (up to > 99% ee).Keywords: asymmetric catalysis; C À C bond formation; conjugate addition; copper; phosphoramidite ligands; zincThe asymmetric conjugate addition (ACA) of organometallic reagents to a,b-unsaturated carbonyl compounds has been the subject of intensive research activity in the past few years.[1] However, highly enantioselective catalytic procedures which make use of acyclic unsaturated carboxylic acid derivatives are rare.[2] The high conformational mobility of these species, together with the presence of only feeble substrate-catalyst steric and electronic interactions, makes the design of effective highly enantioselective systems a real challenge. Whereas chiral imides have been widely used to perform efficient ACA in the context of a chiral auxiliary approach, [3] the addition of alkylmetals to the enantiotopic faces of a,b-unsaturated imides remained problematic until Hoveydas recent report on the asymmetric addition of dialkylzinc reagents to N-acyloxazolidinones promoted by modular triamide phosphanes.[4] However, high enantioselectivities were reached only with b-alkyl derivatives whereas, for example, simple b-aryl derivatives proved to be only poorly reactive and b-vinyl derivatives were not considered. Moreover, it has been suggested that conventional chiral ligands developed for enones were not suitable for the 1,4-addition of R 2 Zn to aliphatic bidentate substrates with chiral metal catalysts, pointing to an apparent need for specialist ligands. [5] We report here the development of a simple, practical and highly enantioselective copper-catalyzed 1,4-addition of alkylmetals to acyclic a,b-unsaturated carboxylic acid derivatives, based on the use of modular (bidentated) cyclic imides and the commercially available phosphoramidite chiral ligand 1, developed by Feringa et al. [6] We recently reported a new copper-catalyzed ACA of organometallic reagents to a,b-unsaturated lactams bearing appropriate protecting-activating groups on the nitrogen atom.[7] The use of carbonyl protecting groups on the endocyclic nitrogen of g-and d-lactams was essential to attain their reactivity and to reach high ees of the corresponding conjugate adducts. In the search for a new carbonylic protecting-activating group for the nitrogen, we considered the 2-butenoyl moiety. The copper-phosphoramidite (R,S,S)-1 catalyzed addition of Et 2 Zn to compounds 2a and b, each containing two conjugated double bonds of a different nature, afforded a reaction mixture in which the addition occurred predominantly on the acyclic framework, to give adducts 3 with a moderate to good enantioselectivity (Scheme 1).The use of imides 5a a...

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