Catalytic Asymmetric Formal Insertion of Aryldiazoalkanes into the C–H Bond of Aldehydes: Synthesis of Enantioenriched Acyclic α-Tertiary Aryl Ketones

Abstract

A novel, catalytic enantioselective route to synthesize a variety of α-tertiary aryl ketones via a boron Lewis acid promoted formal insertion of aryldiazoalkane into the C-H bond of both aromatic and aliphatic aldehydes is described. In the presence of chiral (S)-oxazaborolidinium ion catalyst 1, the reaction proceeded in good yields (up to 94%) with excellent enantioselectivities (up to 99% ee).

Boron‐Based Catalysts for C−C Bond‐Formation Reactions

“…Ryu and co‐workers explored a series of C−C bond‐formation reaction between diazoacetates compounds and various carbonyl substrates (Scheme ) . With catalyst 124 , highly functionalized chiral cyclopropane derivatives 134 were obtained by Michael‐initiated cyclopropanation of α,β‐substituted aldehydes 133 with aryl and alkyl diazoacetates 132 .…”

“…Interestingly, the reactions of aldehydes 139 with alkyl diazoacetate substrates 132 in the presence of catalyst 128 in toluene or 129 in propionitrile led to different chiral products 140 and 141 , respectively (R 7 group versus hydride migration) . Moreover, the insertion of aryldiazoalkanes 132 into the C−H bond of aldehydes 139 could proceed smoothly in the presence of catalysts 130 or 131 to give a variety of enantioenriched α‐tertiary aryl ketones 140 …”

Catalytic Enantioselective Synthesis of 2,5‐Dihydrooxepines

“…Notably,diazo compounds with along alkyl chain or as terically hindered alkyl group successfully reacted with a-bromoacrolein to provide the corresponding 2,5-dihydroox-epine products in moderate to high yield and excellent ee (entries 5-7). While the reactivity of g-aryl-a-vinyldiazoesters was lower than that of g-alkyl-a-vinyldiazoesters,e nantioselective formation of chiral 2,5-dihydrooxepines with aryl substituents proceeded with high yields and excellent enantioselectivity up to 99 %(entries [8][9][10][11][12].…”

“…Va rious g-alkyl-a-vinyl diazo compounds were successfully applied, resulting in high yields and excellent enantioselectivity (entries 1-7). While the reactivity of g-aryl-a-vinyldiazoesters was lower than that of g-alkyl-a-vinyldiazoesters,e nantioselective formation of chiral 2,5-dihydrooxepines with aryl substituents proceeded with high yields and excellent enantioselectivity up to 99 %(entries [8][9][10][11][12]. This catalytic system was also successfully applied to the reaction of a-vinyl a-diazo Weinreb amide to furnish highly optically active 2,5-dihydrooxepine 2bin 72 %yield and 95 % ee (entry 2).…”

“…[4c] Indeed, using this approach for the formation of oxepine derivatives is discouraged due to the multiple steps required to prepare chiral cis-1-formyl-2-vinylcyclopropanes (FVCs) for such arearrangement reactions. [6] Recently,o ur group has reported highly enantioselective catalytic Michael addition initiated cyclopropanations [7] using diazoesters as ylides with the chiral oxazaborolidinium ion [8] (COBI) as aL ewis acid catalyst. We envisioned that the reaction of substituted acroleins with vinyldiazoester would generate chiral cis-1-formyl-2-vinylcyclopropanes (FVCs; 1), which are ideally substituted for subsequent retro-Claisen rearrangement to provide highly functionalized 2,5-dihydrooxepines (2;Scheme 1).…”