Lanthanum Tricyanide-Catalyzed Acyl Silane−Ketone Benzoin Additions and Kinetic Resolution of Resultant α-Silyloxyketones

Abstract

We report the full account of our efforts on the lanthanum tricyanide-catalyzed acyl silane-ketone benzoin reaction. The reaction exhibits a wide scope in both acyl silane (aryl, alkyl) and ketone (arylalkyl, alkyl-alkyl, aryl-aryl, alkenyl-alkyl, alkynyl-alkyl) coupling partners. The diastereoselectivity of the reaction has been examined in both cyclic and acyclic systems. Cyclohexanones give products arising from equatorial attack by the acyl silane. The diastereoselectivity of acyl silane addition to acyclic α-hydroxy ketones can be controlled by varying the protecting group to obtain either FelkinAhn or chelation control. The resultant α-silyloxyketone products can be resolved with selectivity factors from 10 to 15 by subjecting racemic ketone benzoin products to CBS reduction.

Photochemically Induced Silylacylations of Alkynes with Acylsilanes

“…In contrast, analogous silylacylations starting from acylsilanes appear to be under‐represented2 although arguably leading to valuable synthetic products (Scheme ). Only recently, acylations of aldehydes (benzoin condensations),3a–c ketones,3d,e α,β‐unsaturated carbonyls,3f–h nitrones,3i and imines3j with acylsilanes have been reported, which involve the intermediacy of polarity‐reversed carbonyl anions being formed by catalysts such as KCN, La(CN) 3 , metallophosphites, or thiazolium salts 3. Alkynyl‐substituted acylsilanes can cyclize under rhodium catalysis, but subsequently the silyl group is lost 4.…”

Catalytic Non‐Enzymatic Kinetic Resolution

“…In the same area, the KR of α‐silyloxy ketones was recently achieved through the CBS reduction methodology by Johnson et al. As shown in Scheme , the unreacted α‐silyloxy ketones were obtained with selectivity factors in a range of 10–15 by using catalyst 105 255. It must be noted that this methodology was limited to aryl methyl ketones since other substrates including dialkyl, vinyl alkyl, and alkynyl alkyl ketones resulted in very little discrimination between the enantiomers.…”

Organocatalyzed Kinetic Resolution of α-Functionalized Ketones: The Malonate Unit Leads the Way

“…However, a thorough survey of the history of KR showed that, although the resolution of α-functionalized ketones can be dated back to 1941 by Woodward’s seminal report, the field has been extremely underdeveloped (Scheme c). Before 2001, only stoichiometric chiral reagents were used by Yamamoto, Narasaka, and Brown to resolve α-alkylated cyclic ketones; the first catalytic KR of α-substituted cyclic ketones was reported by Overman et al in 2001 . Not until 2010, Johnson and Tarr disclosed the first catalytic KR of acyclic α-substituted ketones using CBS reduction, but the efficiency is low with a selectivity factor ( s ) of 13.8 observed .…”