Chiral Allenes via Alkynylogous Mukaiyama Aldol Reaction

Abstract

Herein we describe the development of a catalytic enantioselective alkynylogous Mukaiyama aldol reaction. The reaction is catalyzed by a newly designed chiral disulfonimide and delivers chiral allenoates in high yields and with excellent regio-, diastereo-, and enantioselectivity. Our process tolerates a broad range of aldehydes in combination with diverse alkynyl-substituted ketene acetals. The reaction products can be readily derivatized to furnish a variety of highly substituted enantiomerically enriched building blocks.

Catalytic Enantioselective Simultaneous Control of Axial Chirality and Central Chirality in Allenes

“…General Information. 1 H NMR, 13 C NMR, and 19 F NMR spectra were recorded in CDCl 3 using a 300 MHz NMR spectrometer ( 1 H at 300 MHz, 13 C at 75 MHz, 19 F at 282 MHz). Mass spectra (MS) and high-resolution mass spectra (HRMS) were carried out using electron impact ionization (EI) or electron spray ionization (ESI).…”

“…Catalytic enantioselective syntheses are always the most atom-economic and efficient method in asymmetric synthesis. Recently, transition metal-catalyzed enantioselective constructions of the axial chirality of allenes from 2-bromo-1,3-butadienes (path a), [12] racemic propargylic carbonates (path b), [13] stereo-defined enol triflates (path c), [14] conjugated enynes (path d), [15] and ketenes (path e), [16] etc., [17] have been developed; in addition, Maruoka and List et al applied the nucleophilic 1,2-addition of allenyl anions with aromatic imines or aldehydes (path f); [18,19] Feng et al developed the chiral Lewis acid-catalyzed rearrangement of propargylic cyclic enol ethers (path g) or conjugate addition of malonate with stereo-defined 1-aryl-1-en-3-ynes (path h); [20,21] These strategies show a great potential with very promising diastereoselectivities in some cases (Scheme 1A). On the other hand, racemic 2,3-allenol derivatives have successfully been applied for the generation of optically active allenes with a central or axial chirality under the catalysis of a palladium catalyst via the "allene-asymmerization" strategy with different chiral ligands (Scheme 1B, eqs.…”

Enantio‐ and Diastereoselective Synthesis of Chiral Allenes by Palladium‐Catalyzed Asymmetric [3+2] Cycloaddition Reactions

“…Several traditional approaches utilize common chemical transformations, such as [3,3] and [2,3] sigmatropic rearrangements, S N 2′ displacements, and reductive transposition of chiral propargyl precursors to form enantiomerically enriched allenes. More recent methods have employed traditional catalytic asymmetric organocatalytic processes, such as a Mannich reaction, an alkynylogous Mukaiyama aldol reaction, or a three‐step sequence including a Petasis reaction . Furthermore, metal‐catalyzed asymmetric allene syntheses have been developed based on transformations of achiral dienes, terminal alkynes, or vinyl triflates .…”

Enantioselective Synthesis of Allenes by Catalytic Traceless Petasis Reactions

“…32 Organocatalytic methods have been developed recently, 33–36 such as an enantioselective alleno-Mannich reaction employing phase-transfer catalysis 35 and an enantioselective alkynylogous Mukaiyama aldol reaction using a chiral phosphoric acid catalyst. 36 While significant advances have been made, the development of broadly useful and convergent strategies to synthesize enantioenriched chiral allenes from achiral precursors remains a significant challenge.…”