Stereo- and Site-Selective Conversion of Primary Alcohols to Allylic Alcohols via Ruthenium-Catalyzed Hydrogen Auto-Transfer Mediated by 2-Butyne

Abstract

The first enantioselective ruthenium-catalyzed carbonyl vinylations via hydrogen autotransfer are described. Using a ruthenium-JOSIPHOS catalyst, primary alcohols 2a–2m and 2-butyne 1a are converted to chiral allylic alcohols 3a–3m with excellent levels of absolute stereocontrol. Notably, 1°,2°-1,3-diols participate in site-selective C–C coupling, enabling asymmetric carbonyl vinylation beyond premetalated reagents, exogenous reductants, or hydroxyl protecting groups. Using 2-propanol as a reductant, aldehydes dehydro-2a, 2l participate in highly enantioselective 2-butyne-mediated vinylation under otherwise identical reaction conditions. Regio-, stereo-, and site-selective vinylations mediated by 2-pentyne 1b to form adducts 3n, 3o, and epi-3o also are described. The tiglyl alcohol motif obtained upon butyne-mediated vinylation, which is itself found in diverse secondary metabolites, may be converted to commonly encountered polyketide stereodiads, -triads, and -tetrads, as demonstrated by the formation of adducts 4a–4d. The collective mechanistic studies, including deuterium labeling experiments, corroborate a catalytic cycle involving alcohol dehydrogenation to form a transient aldehyde and a ruthenium hydride, which engages in alkyne hydrometalation to form a nucleophilic vinylruthenium species that enacts carbonyl addition. A stereochemical model for carbonyl addition invoking formyl CH···I­[Ru] and CH···OC­[Ru] hydrogen bonds is proposed based on prior calculations and crystallographic data.

Historical perspective on ruthenium-catalyzed hydrogen transfer and survey of enantioselective hydrogen auto-transfer processes for the conversion of lower alcohols to higher alcohols

“…Remarkably, when the latter conditions are applied to 2-butyne, alkyne-to-allene isomerization is interrupted at the stage of intermediate vinylruthenium species via carbonyl addition to form products of alkenylation (Scheme 8). 28,29 This divergent reactivity suggests acetylenic substituents larger than methyl ( i.e. aryl or sec -alkyl) stabilize a syn -periplanar conformation of the carbon–ruthenium and propargylic C–H bonds, reducing the entropy of activation for β-hydride elimination to accelerate allene formation.…”

Recent Progress in Upgrading of Alcohol and Amine via Asymmetric Dehydrogenative Coupling

“…该反应底物范围广, 具有不同电性和带有各类杂环的底 物均能很好地兼容, 并且这一催化体系还可顺利应用于 天然产物(-)-Crataegusanoids 的全合成中. 随后, 该课 题组 [32] 还将 2-丁炔应用于醇的不对称脱氢偶联中, 以良 好的收率和优秀的对映选择性得到手性烯丙醇产物 (Scheme 6, c 图式 6 钌催化的内炔与伯醇的不对称脱氢偶联 Scheme 6 Ruthenium-catalyzed asymmetric dehydrogenative coupling of internal alkyne and primary alcohol α 位的烯丙基化, 能以专一的选择性得到 Z 式手性高烯 丙醇产物 [33] , 该反应具有专一的化学选择性, 并未发生 醇 α 位的炔基化反应.…”

Iridium-, Ruthenium-, and Nickel-Catalyzed C–C Couplings of Methanol, Formaldehyde, and Ethanol with π-Unsaturated Pronucleophiles via Hydrogen Transfer

“…Hence, carbonyl addition from the vinylruthenium intermediate becomes slow with respect to β-hydride elimination to form an allene. 25 Consequently, a dual catalytic process is enacted, wherein alkyne-to-allene isomerization is followed by allene-ethanol C− C coupling by way of an allylruthenium nucleophile. 26 Using the precatalyst RuI(CO) 3 (η 3 -C 3 H 5 ) in combination with the JOSIPHOS ligand SL-J009-1, enantioselective anti-(α-aryl)allylations of ethanol were achieved.…”