Kinetic resolution of donor-functionalised tertiary alcohols by Cu–H-catalysed stereoselective silylation using a strained silicon-stereogenic silane

Abstract

A series of propargylic tertiary alcohols decorated with an sp2-hybridised nitrogen donor were kinetically resolved by reagent-controlled dehydrogenative Si-O coupling with a strained, highly reactive silicon-stereogenic cyclic silane.

Broad-spectrum kinetic resolution of alcohols enabled by Cu–H-catalysed dehydrogenative coupling with hydrosilanes

“…Reactions were routinely run for 18 h to achieve synthetically useful conversions. To boost the reactivity28, we tested cyclic and, hence, more Lewis-acidic hydrosilane 2n but the enormous reactivity gain was at the expense of selectivity ( s =3.51, entry 14). Also, alkoxy-substituted hydrosilanes, such as (EtO) 3 SiH ( 2o ), reacted rapidly yet without any asymmetric induction (entry 15).…”

“…Hence, the reported values are not exact but rather an approximation of the order of magnitude. While the present protocol is limited to secondary alcohols, we will now tackle the most difficult class of alcohols in this chemistry, tertiary alcohols28.…”

“…Unlike chlorosilanes, these react without racemization with hydroxy groups. By this, we accomplished the reagent-controlled kinetic resolution of alcohols with an achiral monodentate phosphine ligand at the copper(I) atom2627282930. We were later able to turn this kinetic resolution into a catalyst-controlled process with a chiral monodentate ligand and achiral hydrosilanes31.…”

Catalytic Silylations of Alcohols: Turning Simple Protecting‐Group Strategies into Powerful Enantioselective Synthetic Methods

“…Attack of the nucleophile on the silicon atom results in the formation of ahypervalent silyl species,which not only serves as an activated silylating agent, but also controls the enantioselectivity of the reaction. Whereas pyridine-type and oxazole subunits were effective donor moieties,benzothiazole-or thiophene-functionalized alcohols were unsuitable.O estreich and co-workers also applied this elegant concept to the kinetic resolution of challenging alcohol structures,i ncluding propargylic tertiary alcohols [32] and trifluoromethyl-substituted carbinols. [27, 2b] In 2005, the Oestreich group reported akinetic resolution of chiral secondary alcohols [28] with silicon-stereogenic silanes.…”

Kinetic Resolution of Quaternary and Tertiary β‐Hydroxy Esters

“…[7] Hoveyda, Snapper, and co-workers also used a peptide based catalyst for selective silylation of 1,2diols, including three examples of tertiary alcohols, [8a] as well as the desymmetrization of triols. [9] Matsunaga, Shibasaki, and co-workers also developed a resolution of tertiary nitroaldols through a retro-nitroaldol reaction catalyzed by mixed La/Li heterobimetallic complexes. [9] Matsunaga, Shibasaki, and co-workers also developed a resolution of tertiary nitroaldols through a retro-nitroaldol reaction catalyzed by mixed La/Li heterobimetallic complexes.…”