Kinetic Resolution of Tertiary Alcohols by Chiral Organotin-Catalyzed O-Acylation

Abstract

A novel highly enantioselective method for the kinetic resolution of racemic tertiary alcohols has been achieved through chiral organotin-catalyzed intermolecular acylation of the hydroxyl group. This process has demonstrated a broad substrate scope (both alkyl- and aryl-substituted tertiary alcohols) with high enantioselectivity under mild reaction conditions, affording the corresponding products and the recovered tertiary alcohols with high enantioselectivities, with s factors up to >200.

A highly enantioselective approach towards optically active γ-amino alcohols by tin-catalyzed kinetic resolution of 1,3-amino alcohols

“…Finally, based on the results stated above and previous reports, 12,16 a possible mechanism was proposed (Scheme 5). First, the chiral organotin catalyst C6 and 1,3-amino alcohol 1 bond covalently to form the diastereomers I-1 and I-2 .…”

“…However, the scope was limited and the selectivity was not satisfactory, with many substrates. The results mentioned above 12,13 led us to think if we could realize the highly enantioselective KR of 1,3-amino secondary alcohols in general and the stereocontrol effect. Combined with our interest in selective modification of hydroxyl groups 14 in polyols, here we describe an efficient method to obtain optically active 1,3-amino alcohols mediated by a chiral organotin catalyst (Scheme 1b).…”

“…Recently, we disclosed a highly enantioselective KR of β-amino alcohols using a chiral organotin catalyst. 12 Simultaneously, an γ-amino alcohol was studied under reaction conditions described previously via a six-membered stannylene aminal intermediate. However, the scope was limited and the selectivity was not satisfactory, with many substrates.…”

Kinetic resolution of racemic tertiary allylic alcohols through SN2′ reaction using a chiral bisphosphoric acid/silver(i) salt co-catalyst system

“…In contrast to the catalytic KR of racemic secondary alcohols, 4 reliable methods for the non-enzymatic KR of tertiary alcohols remain few. 5–9 Several groups have reported the use of chiral Lewis base (nucleophilic) catalysts 6 and chiral transition metal catalysts. 7 In the methodologies reported for the KR of racemic tertiary alcohols in recent years, chiral phosphoric acids (CPAs), which are one of the most powerful and privileged organocatalysts employed in a broad range of enantioselective transformations, 10 have proven to be excellent catalysts.…”

Pseudo-enantiomeric coupling reagents for predictable incorporation into the peptide chain D and/or L amino acid residue of racemic substrates

“…[7][8][9][10] These include kinetic resolution using chiral 4-dimethylaminopyridine (DMAP) analogues, [11][12][13][14] amidine based catalysts, 15 phosphines, [16][17][18] amines, 19 and others. 20,21 Scheme 1. Attachment of rac-Pg-NH-Aaa*-COOH to the chiral amino-component H2N-Bbb*-COOR using chiral coupling reagent H-Y* proceeds with diastereoselectivity controlled by the three stereogenic centres already present in the substrates and an additional stereogenic centre in the tetrahedral intermediate.…”