Catalytic Synthesis of Enantiopure Chiral Alcohols via Addition of Grignard Reagents to Carbonyl Compounds

Abstract

Remarkable progress in the enantioselective addition of Grignard reagents to carbonyl compounds has been made over the past decade. This enantioselective transformation now allows the use of these challenging reactive nucleophiles for the formation of chiral alcohols using catalytic amounts of chiral ligands. This review summarizes the developments in the area.

Enantioselective vinylation of aldehydes with the vinyl Grignard reagent catalyzed by magnesium complex of chiral BINOLs

“…Optical rotations were recorded on a polarimeter. 1 H nuclear magnetic resonance (NMR) and 13 C NMR spectra were measured on 200 and 100 MHz spectrometers, respectively, in CDCl 3 with TMS as an internal standard; chemical shifts are reported in parts per million. The determination of ee values was carried out using chiral high-performance liquid chromatography (HPLC) with an OD-H, OJ-H, or AS-H column.…”

“…Because of greatly reactive, however, the catalytic asymmetric addition of Grignard reagents to aldehydes is typically challenging . Only recently successful strategies were developed in access to highly enantiopure secondary alcohols via catalytic asymmetric Grignard reactions . The groups of Harada, Xu, and Yus utilized superstoichiometric Ti (O i ‐Pr) 4 to transmetallate RMgX (Br, Cl) to less reactive R‐Ti (O i ‐Pr) 3 , and then R‐Ti (O i ‐Pr) 3 highly enantioselectively delivered R group to aldehydes catalyzed by chiral diol‐Ti (O i ‐Pr) 2 complexes.…”

“…[1][2][3][4][5][6][7][8][9][10] Only recently successful strategies were developed in access to highly enantiopure secondary alcohols via catalytic asymmetric Grignard reactions. [11][12][13] The groups of Harada, [14][15][16] Xu, 17,18 and Yus 19,20 utilized superstoichiometric Ti (Oi-Pr) 4 to transmetallate RMgX (Br, Cl) to less reactive R-Ti (Oi-Pr) 3 , and then R-Ti (Oi-Pr) 3 highly enantioselectively delivered R group to aldehydes catalyzed by chiral diol-Ti (Oi-Pr) 2 complexes. Our group demonstrated that the additive bis([2-[N,N′-dimethylamino)]thyl) ether (BDMAEE) effectively deactivated the reactivity of Grignard reagents and then similarly transmetallated R functional group of RMgBr to R-Ti (Oi-Pr) 3 by using stoichiometric Ti (Oi-Pr) 4 .…”

Catalytic Enantioselective Addition of Organozirconium Reagents to Aldehydes

“…The catalytic enantioselective 1,2-addition reaction of organometallic reagents to carbonyl compounds is one of the most efficient approaches to chiral alcohols. This transformation has been extensively studied with dialkylzinc [ 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ] and trialkylaluminium [ 18 , 19 , 20 ] reagents; more recently, excellent results with Grignard [ 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 ] and organolithium [ 36 , 37 , 38 ] reagents have also been reported. The high reactivity and sometimes pyrophoric character of these premade, non-stabilized organometallic nucleophiles, however, restricts the implementation of these methodologies in industrial processes and large-scale reactions [ 39 ].…”

Cobalt-Catalyzed Carbonylative Cross-Coupling of Alkyl Tosylates and Dienes: Stereospecific Synthesis of Dienones at Low Pressure

“…3 This approach capitalizes on the array of methods available for preparing simple building blocks stereoselectively (e.g., chiral, non-racemic secondary alcohols). 4 Despite the potential for such processes, they are currently limited in scope.…”