While the conjugate addition reaction has been widely studied over many years, effective methods for the asymmetric addition of alkyl groups to acyclic α,β-unsaturated carbonyls are less common. Importantly, in this report both alkyl and aryl substitution at the β-position of the α,β-unsaturated N-acylpyrrolidinone gave good enantioselectivities. Both Et2Zn and i-Pr2Zn gave good results with the former outperforming the latter.

A new and practical way to introduce an alkyl fragment in the β-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 α,β-unsaturated carboxylic acid, were found to be the substrates of choice featuring good reactivity and high enantioselectivities (up to > 99% ee).

A conceptually new regioselective and highly syn-stereoselective intermolecular Friedel-Crafts-type O-alkylation of phenols with aryl epoxides by the use of appropriately substituted aryl borates is reported. The carbon-carbon bond formation occurs in neutral and mild conditions without the need for external Lewis acids or transition metal catalysts. (c) 2005 Elsevier Ltd. All rights reserved.

Abstract An unprecedented catalytic asymmetric ring-opening of easily accessible 2,3-heterosubstituted norbornenes with hard alkyl metals (R-M), is able to give a practical regio- and stereoselective access to hetero-functionalized alkyl cyclopentenes in an enantioenriched form. The copper-catalyzed desymmetrization reaction with trialkylaluminums of sterically hindered and rigid, tri- or tetracyclic Diels-Alder adducts, easily available by cycloaddition reaction of cyclopentadiene with 4-phenyl-urazole and 2,3-phthalazine-1,4-dione, proved to be particularly efficient. Interestingly, the chirality of the amine part of the BINOL-based phosphoramidite is able to impose the absolute stereochemistry of the corresponding adducts.

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 conceptually new, simple and practical method for the syn-nucleophilic displacement of aryl and vinyl epoxides and aryl aziridines with (substituted) phenols, using aryl borates as activating nucleophiles under neutral conditions, is reported.

4-Alkyl-2,5,7-cyclooctatrienols with high enantiomeric purities (93-96% ee), obtained by an improved copper-phosphoramidite-catalyzed addition of dialkylzinc reagents to cyclooctatetraene monoepoxide, have been subjected to simple and practical manipulations. Simple esterification reactions are able to deliver new functionalized isomeric 8-alkyl-7-acyloxybicyclo[4.2.0]octa-2,4-dienes through a domino sequence of rearrangement reactions, in good yields. Moreover, new 4-alkyl-substituted-2,6-cyclooctadienones with high optical purity can be efficiently obtained from gramscale reactions by simple thermal treatment. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004).

The reactions of some organocopper reagents with cyclic 2-alkenyl aziridines were examined. The stereoselectivity of the addition reaction of dialkylzinc can be strongly influenced by the use of phosphoramidites as ligands for copper. Chiral copper complexes of 2,2′-binaphthyl-based phosphoramidites were shown to be highly effective catalysts for the regio- (SN2′) and anti-stereoselective addition of dialkylzinc reagents to these compounds according to a kinetic resolution protocol. The corresponding new cyclic allylic amine reaction products were obtained with a good enantioselectivity (83% ee).

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.

The copper-catalysed addition of organometallic reagents (Grignard and dialkylzinc) to new vinyl diepoxides was examined. Cyclic vinyl diepoxides undergo clean S(N)2' reactions to afford oxa-bridged systems of various sizes after a domino intramolecular O-alkylation reaction. Acyclic vinyl diepoxides are alkylated in good yields and with good regioselectivities, and a new catalytic enantioselective desymmetrization reaction to afford an enantioenriched allylic epoxy alcohol by the use of catalytic amounts of a copper phosphoramidite complex was demonstrated. Remarkable differences in terms of reactivity and selectivity are found when different organocopper reagents, generated in situ, are employed.

[reaction: see text] The first alkylative and enantioselective ring-opening of COT-monoepoxide (1) without the occurrence of any ring-contraction-isomerization by the use of in situ-formed organocuprates is reported. Because of the particular geometric constraint of compound 1, this work reports the largest deviation from coplanarity between the pi-orbital of the double bond and the sigma-bond connecting the leaving group ever observed for an S(N)2'-cuprate alkylation.

The regiochemical behavior of the pairs of diastereoisomeric activated aziridines 1–8 deriving from the cyclohexane system, bearing a remote O-functionality, was determined in the acid methanolysis in the condensed phase (cd-phase) and in the reaction with MeOH in the gas-phase using a gaseous acid (D3+) as the promoting agent. The results obtained in the opening process of the cis diastereoisomers indicate the constant incursion in the gas phase of D+(corresponding to H+)-mediated chelated bidentate species able to modify the regiochemical result found in the methanolysis in the cd-phase.

The regiochemical behavior of the title deoxy anhydrosugars, prepared in an enantioselective way starting from methyl α-d-glucopyranoside, was examined in opening reactions, both under standard and chelating conditions. The results clearly indicate the influence of the reaction conditions and the importance of the relative orientation of the methyl group with respect to the oxirane ring on the regiochemical outcome of these epoxides. An useful inversion of regioselectivity is obtained in some cases.

[reaction: see text] An unprecedented copper phosphoramidite catalyzed enantioselective alkylative ring-opening reaction of oxabenzonorbornadiene derivatives with dialkylzinc reagents is reported. The reaction shows high levels of anti-stereoselectivity (up to anti/syn >99:1), complementary to the Pd(0)-catalyzed syn-selective ring-opening protocol, allowing a new entry to anti-dihydronaphthols with high enantioselectivity (up to 99% ee).

Chiral recognition leads to enantio- and regiodivergent reactivity: An unusual regiodivergent catalytic kinetic resolution has been accomplished for the first time in an organometallic reaction in which a C-C bond is formed. Chiral copper complexes of the non-racemic phosphoramidite ligand L* discriminate the enantiomers of semirigid vinyloxiranes (having a blocked s-cis or s-trans conformation) to give separable regioisomeric products with very high stereocontrol in a two-step process.

The first catalytic asymmetric synthesis of both (R)-(+)-and (S)-(-)-4-methyl-2-cyclohexen-1-one and a new and improved synthesis of both enantiomers of (IS,4S)-(-) and (1R,4R)-(+)-4-methyl-2-cyclohexen-1-ol was developed on a multigram scale. The key step of this approach is the asymmetric catalyzed addition of Me2Zn (S(N)2'-pathway) to racemic 1,3-cyclohexadiene monoepoxide. This step has been optimized as for as enantio- and regioselectivities, and work-up procedures. The striking ligand accelerated catalysis exhibited by the chiral copper complex of the 2,2'-binaphthyl-based phosphoramidite, herein reported, permitted a very low catalyst loading (0.6 mol%).

The first catalytic enantioselective trapping of symmetrical and racemic arene oxides with organometallic reagents is reported.