Highly Enantioselective Catalytic Conjugate Addition and Tandem Conjugate Addition–Aldol Reactions of Organozinc Reagents

Abstract

COMMUNICATIONSX-ray crystal structure analysis of [ (Li+)2(Zz-)(OEt,),(thf)2]: C44H76Li201r Pi, a = 9.782(1), b=14.594(1), c=15.640(1) A, a=74.999(2), p=81.977 (2), y = 83.417(2)", V=2128.34 A3, Z=2, pcalcd = 1.07 gem-), p =0.060 mm-I, T = 150 K, crystal dimensions ca. 0.25 x 0.50 x 0.50 mm3, 90 frames, 26428 measured (8101 unique) reflections, R = 0.0472 and R, = 0.0475 for 5823 reflections with t > 6o(l), maximum and minimum peak in final Fourier difference synthesis 0.58 and -0.42 e k 3 . Unit weights were used in the refinements. The asymmetric unit consists of half of a molecule of [(Li'),(ZZ-)(OEt2),] and half a molecule [(Li+)2(22-)(thf)4]. each located about an inversion center. X-ray crystal structure analysis of [ (K+)2(22-)( [18]crown-6),1: C26H88KZ0,2, P2.,ln, u = 13.959(1), b = 10.403(1), C = 19.733(1) A, b= 107.376(1)", V= 2740.31 A3, Z = 2, pca,d = 1.19 gcm-', # =0.22 mm-', T = 150 K, crystal dimensions ca. 0.20 x 0.25 x 0.40 mm', 90 frames, 29555 measured (6266 unique) reflections, R = 0.0422 and R,=0.0464 for 5403 reflections with t>3o(I), maximum and minimum peak in final Fourier difference synthesis 0.36 and -0.23 e k 3 . A weighting scheme based on an optimized three-coefficient Chebyshev polynomial was used in the refinements [31]. General crystallographic information: Data were collected on an Enraf-Nonius DIP 2000 image plate diffractometer using graphite-monochromated Mo,, radiation (step of 2" between frames, B, , = 26"). Corrections were made for Lorentz and polarization effects [32]. The structures were solved by direct methods using SIR92[33] and refined by using full-matrix least-squares. Hydrogen atoms were fixed in geometrically idealized positions and allowed to ride on their attached carbon atoms. Corrections for the effects of anomalous dispersion and isotropic extinction (through an overall extinction coefficient) [34] but not for absorption, were made in the final stages of refinement. All crystallographic calculations were performed by using the Oxford CRYSTALS system[35] running on a Silicon Graphics Indigo R4000 computer. Crystallographic data (excluding structure factors) for the structures reported in this paper have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-100693. Copies of the data can he obtained free of charge on application to The Director, CCDC, 12 Union Road, Cambridge CB21 lEZ, UK

Asymmetric Organocopper Chemistry: Cu‐Catalyzed Conjugate Addition and Allylic Substitution

“…30 Functionalized dialkylzincs afford comparable enantioselectivities as Et2Zn. 13,15,21 The compatibility of R2Zn with many functional groups is clearly an advantage of the methodology. 31 However, it should be pointed out that diaryl or divinyl zinc reagents are scarce.…”

Enantioselective synthesis of (R)-isocarvone from (S)-perillaldehyde

“…7 Nakao and co-workers, 17 in their reported results on the enantioselective 1,4-addition of tetraorganosilicon reagents under the rhodium-chiral diene catalysis to α,β-unsaturated carbonyl acceptors, have prepared (R)-3-isopropenylcyclohexanone (4a) with a high enantiomeric excess (96 %) from cyclohexen-2-one. The higher saturated 3-isopropylcyclohexanone (4b) can be prepared more easily with a high yield and enantiomeric excess by catalytic 1,4-addition of organometallic reagents to cyclohexenone, 18 by organocatalytic asymmetric transfer hydrogenation of 3-isopropyl-2-cyclohexenone 19 or by a chemoenzymatic process. 20 The (R)-enantiomer form of isocarvone (1) has also been shown to be a valuable building block for the synthesis of the complex target (C 1 -C 24 ) carbon framework of Norzoanthamine, which has a broad spectrum of potent biological activities.…”

Copper-catalyzed asymmetric conjugate addition of Grignard reagents to cyclic enones

“…The development of highly enantioselective catalytic versions of this key transformation is of paramount importance (2)(3)(4)(5)(6)(7)(8)(9). In recent years, the design of new chiral ligands and catalysts has led to the realization of asymmetric Michael additions (10,11) and conjugate additions of dialkylzinc reagents (12,13) as well as arylboronic acids (14) with excellent levels of stereocontrol. For the asymmetric conjugate addition of alkylmetals, the subject of the present study, particularly effective methods based on alkylzinc reagents are now available for various cyclic enones (12,15) including the usually problematic cyclopentenones (16,17), lactones (18), nitroalkenes (19,20), and acyclic enones (21).…”

“…In recent years, the design of new chiral ligands and catalysts has led to the realization of asymmetric Michael additions (10,11) and conjugate additions of dialkylzinc reagents (12,13) as well as arylboronic acids (14) with excellent levels of stereocontrol. For the asymmetric conjugate addition of alkylmetals, the subject of the present study, particularly effective methods based on alkylzinc reagents are now available for various cyclic enones (12,15) including the usually problematic cyclopentenones (16,17), lactones (18), nitroalkenes (19,20), and acyclic enones (21). Meanwhile, considerable difficulties have been experienced in attempts to reach high stereoselectivities in transition metalcatalyzed 1,4-addition of other organometallic reagents.…”