Catalytic Enantioconvergent Allenylation of Aldehydes with Propargyl Halides

Abstract

α-Allenol is a versatile synthon in organic synthesis. The catalytic asymmetric synthesis of α-allenols from readily available starting materials remains a prominent challenge, especially when simultaneous control over axial and central chirality is required. Herein, we describe the Cr-catalyzed enantioconvergent allenylation of aldehydes with racemic propargyl halides to rapidly access a wide range of chiral αallenols with adjacent axial and central chiralities. This method features excellent regio-, diastereo-and enantioselectivity control with broad substrate scope, and provides facile access to all four stereoisomers when allied with a Mitsunobu reaction. Preliminary mechanistic studies support radicalbased reaction pathways. The synthetic utility is demonstrated by the application in late-stage functionalization and the formal total synthesis of (+)-varitriol.

Asymmetric 1,4-functionalization of 1,3-enynes via dual photoredox and chromium catalysis

“…However, the reactivity of N-heteroaromatic aldehydes is rarely demonstrated in previous NHK reactions. As disclosed in recent studies, they generally led to poor yields, including our stereoconvergent allenylation reaction (20-23) 50,[53][54][55] . Aliphatic aldehydes, substituted with diverse primary or secondary alkyl chains, participated efficiently in this 1,4functionalization of 1,3-enynes (24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39).…”

“…As our ongoing efforts in Cr-catalyzed radical-involved reactions 50 , we anticipate that the propargyl radical, which is in equilibrium with the allenyl radical, could be captured by a chiral chromium complex, and subsequent nucleophilic addition to the aldehyde affords the enantioenriched products (Fig. 1a , bottom).…”

Recent advances in the metal-catalyzed asymmetric synthesis of chiral allenes

“…In 2022, Wang's group presented a Cr-catalyzed enantioconvergent synthesis of chiral α-allenols from racemic propargylic halides and aldehydes. 38 A wide range of chiral α-allenols were provided in high yields, enantioselectivities and diastereoselectivities. A possible mechanism was proposed, as outlined in Scheme 23.…”

The Tetrahydrofuran Motif in Marine Lipids and Terpenes

“…Later on, Qin developed a direct cross-coupling between terminal alkynes and glycosyl acetates, that was applied to the formal synthesiss of (+)-109 and analogues [102]. More recently, Wang and coworkers reported another formal synthesis of (+)-109 [103]. There, they developed a chromium-catalyzed enantioconvergent allenylation of aldehydes to synthesize -allenols from racemic propargyl halides.…”