Enantioselective Ruthenium-BINAP-Catalyzed Carbonyl Reductive Coupling of Alkoxyallenes: Convergent Construction of syn-sec,tert-Diols via (Z)-σ-Allylmetal Intermediates

Abstract

The first catalytic enantioselective ruthenium-catalyzed carbonyl reductive couplings of allene pronucleophiles is described. Using an iodide-modified ruthenium-BINAP-catalyst and O-benzhydryl alkoxyallene 1a, carbonyl (α-alkoxy)­allylation occurs from the alcohol or aldehyde oxidation level to form enantiomerically enriched syn-sec,tert-diols. Internal chelation directs intervention of (Z)-σ-alkoxyallylruthenium isomers, which engage in stereospecific carbonyl addition.

Understanding Halide Counterion Effects in Enantioselective Ruthenium-Catalyzed Carbonyl (α-Aryl)allylation: Alkynes as Latent Allenes and Trifluoroethanol-Enhanced Turnover in The Conversion of Ethanol to Higher Alcohols via Hydrogen Auto-transfer

“…Here, by understanding halide counterion effects , and exploiting trifluoroethanol (TFE)-enhanced turnover, we report an improved catalytic system for alkyne−alcohol C−C coupling, as illustrated by the regio- and enantioselective conversion of ethanol (the most abundant renewable small-molecule carbon source) to enantiomerically enriched homoallylic alcohols. Specifically, using a ruthenium catalyst modified by JOSIPHOS in the presence of TFE, diverse 1-aryl-1-propynes react with ethanol to form branched secondary homoallylic alcohols through a tandem catalytic cycle in which alkyne-to-allene redox isomerization is followed by allene−​aldehyde reductive coupling via hydrogen auto-transfer. − As corroborated by DFT calculations and crystallographic characterization of a series of halide-bound complexes, RuX­(CO)­(η 3 -C 3 H 5 )­(JOSIPHOS), where X = Cl, Br, or I, there exists a halide-dependent diastereomeric preference that defines metal-centered stereogenicity and, therefrom, the absolute stereochemical course of C−C coupling. Whereas the chloride- and bromide-bound catalysts exist as stereoisomeric mixtures, the iodide-bound catalyst exists as a single stereoisomer, enforcing superior levels of enantioselectivity.…”

Confronting the Challenging Asymmetric Carbonyl 1,2-Addition Using Vinyl Heteroarene Pronucleophiles: Ligand-Controlled Regiodivergent Processes through a Dearomatized Allyl–Cu Species

“…The enantioselective coupling of two prochiral molecules constitutes an effective strategy for the construction of multiple vicinal stereogenic centers in a single operation. − In particular, the reaction between prochiral vinyl heterocycles and carbonyl-containing electrophiles such as aldehydes and ketones provides rapid entry to enantiomerically enriched alcohols, which are prominent substructures in pharmaceuticals and natural products (Figure A). − Prototypical approaches to form enantioenriched secondary or tertiary alcohols have relied on utilizing stoichiometric chiral auxiliaries to relay stereochemical information to the product . Catalytic asymmetric approaches to access secondary and tertiary alcohols generally promote the 1,2-carbonyl addition of preformed organometallic reagents with a chiral Lewis acid or base catalyst. − The application of these protocols, however, is frequently complicated by the pregeneration of a stoichiometric amount of highly reactive carbon nucleophiles, limiting the functional group compatibility.…”

Zinc-Mediated Hydroxyallylation of Aldehydes with Cyclopropanols: Direct Access to Vicinal anti-sec,tert-Diols via Enolized Homoenolates

“…4 Recently, Krische disclosed an enantioselective ruthenium-catalyzed reductive coupling of alkoxyallene and aldehyde via (Z)-configured α-alkoxyallylruthenium species, which also afforded syn-diol products (Scheme 1b). 5 Besides the need for deprotection of the alkoxy groups, a common limitation in these reactions concerns the scope of the αsubstituent in the allylmetal species. Marek's approach was limited by the scope of organocopper reagents capable of carbocupration (R = primary alkyl), whereas Krische's method employed only α-methylalkoxyallene due to the difficulty in the preparation of differently substituted alkoxyallenes.…”

“…Marek reported carbocupration/zinc homologation of ynol ethers as a means to generate ( E )-configured α-alkoxyallylzinc species, which reacted with aldehydes to afford syn - sec , tert -diols (Scheme a) . Recently, Krische disclosed an enantioselective ruthenium-catalyzed reductive coupling of alkoxyallene and aldehyde via ( Z )-configured α-alkoxyallylruthenium species, which also afforded syn -diol products (Scheme b) . Besides the need for deprotection of the alkoxy groups, a common limitation in these reactions concerns the scope of the α-substituent in the allylmetal species.…”