The Enantioselective Allylation and Crotylation of Sterically Hindered and Functionalized Aryl Ketones: Convenient Access to Unusual Tertiary Carbinol Structures

Abstract

The development of reagents and catalysts for the enantioselective allylation of ketones has been an important goal in asymmetric synthesis for many years. Over the past decade, some important and seminal advances have been recorded, but most of these require the use of potentially toxic tin-based allyl reagents.[1] More recently, Chong, [2] Shibasaki, [3] Soderquist, [4] and Yamamoto [5] have recorded truly remarkable advances. With only a few notable exceptions, however, the scope of reactions that gives useful levels of efficiency and enantioselectivity remains limited to aryl methyl, cyclohexenyl methyl, and tert-butyl methyl ketones and structurally related derivatives thereof. There is no current solution at all for the enantioselective allylation of several important classes of ketones, including highly sterically hindered aryl alkyl ketones and diaryl ketones. In addition, only limited success has thus far been recorded in enantioselective ketone crotylation reactions, and no method that can produce both the syn and anti diastereomers with high levels of diastereoand enantioselectivity has been reported. Our own recent investigations into the use of strained allylsilanes [6] for enantioselective aldehyde allylations and crotylations [7]

Diastereoselective Allylation of Carbonyl Compounds and Imines: Application to the Synthesis of Natural Products

“…112 As was previously mentioned, phenols were effective directing and activating groups for these allylchlorosilane reagents. 113 Leighton and co-workers also reported the stereoselective allylation of both aliphatic and aromatic aldimines derived from ortho-aminophenols with chiral allylsilanes 14.…”

Silver‐Catalyzed Allenylation and Enantioselective Propargylation Reactions of Ketones

“…[19][20][21] In 2006, the Leighton group reported the highly enantioselective allylation of prochiral 2'-hydroxyphenylketones, where the phenol directing group accelerates reaction rates and differentiates the arenes. [6] To the best of our knowledge, however, enantioselective propargylation of prochiral benzophenones has not been demonstrated. The ability of the silver catalyst to distinguish between two aromatic rings would lead to enantioenriched diaryl carbinols, which are present in a variety of drugs [22] and medicinal agents.…”

“…In the early 1990s, the first catalytic asymmetric methods to form chiral secondary alcohols were reported, spurring renewed interest in the field. [6] Herein, we report silver-catalyzed allenylation and propargylation reactions on a wide range of ketones (Scheme 1). [4,5] Several of these catalyst systems provide high enantioselectivity in additions to methyl ketones.…”

“…Enantioselective propargylation reactions of prochiral diaryl ketones have not been reported, however. [6] Herein, we report silver-catalyzed allenylation and propargylation reactions on a wide range of ketones (Scheme 1). Allenylation predominates in the absence of exogenous ligands, whereas enantioselective propargylation takes place in the presence of a chiral phosphine ligand.…”

Direct and highly regioselective and enantioselective allylation of β-diketones

“…5,7,8,19 We therefore decided to interrogate the ability of crotylsilanes 20 and 21 20 to crotylate β-diketones, and it was found that treatment of acetylacetone and benzoylacetone with trans -crotylsilane 20 led to the isolation of 22 (69%, 89% ee) and 23 (75%, 97% ee), respectively (Fig. 4a).…”