Substrate-Controlled Diastereoselectivity Reversal in NHC-Catalyzed Cross-Benzoin Reactions Using N-Boc-N-Bn-Protected α-Amino Aldehydes

Abstract

The effectiveness of utilizing N-Bn-N-Boc-α-amino aldehydes in cross-benzoin reactions with heteroaromatic aldehydes is demonstrated. The reaction is both chemoselective and syn-selective, making it complementary to the anti-selective cross-benzoin reaction of NHBoc-α-amino aldehydes. Good diastereoselectivity is obtained for a variety of amino aldehydes, including nonhindered ones. A Felkin-Anh model can be used to rationalize the observed diastereoselectivity.

Stereodivergent Catalysis

“…Recently, a switch of diastereoselectivity has been reported by Gravel and co-workers in the cross-benzoin or cross-acyloin reaction catalyzed by an N-heterocyclic carbene (NHC) derived from 137 . , Substrate-controlled diastereodivergent results were observed for the reaction of aldehydes with α-amino aldehydes 136 . In the case of 136a (NHBoc), anti -selective cross-benzoin reaction took place giving α-hydroxyketones 138 with de up to 90% (Scheme ).…”

“…In the case of 136a (NHBoc), anti -selective cross-benzoin reaction took place giving α-hydroxyketones 138 with de up to 90% (Scheme ). On the other hand, when α-amino aldehydes 136b (NBnBoc) were used, syn -selectivity was observed affording products 139 with de up to 82% . The observed diastereoselectivity was rationalized using a Cram-chelate model 138A in the first case and a polar Felkin–Anh TS model 139A for the last case.…”

“… On the other hand, when α-amino aldehydes 136b (NBnBoc) were used, syn -selectivity was observed affording products 139 with de up to 82% . The observed diastereoselectivity was rationalized using a Cram-chelate model 138A in the first case and a polar Felkin–Anh TS model 139A for the last case.…”

Organocatalytic Name Reactions Enabled by NHCs

“…Such a procedure of reaction between aldehydes and paraformaldehyde was reported by Glorius in 2011 [67]. It is worth noting that the chemoselective cross-benzoin reaction with the use of α-aminoaldehydes as electrophilic agents is also possible [68,69].…”

Total Synthesis of (+)-Hyacinthacine A1 Using a Chemoselective Cross-Benzoin Reaction and a Furan Photooxygenation–Amine Cyclization Strategy

“…Previously, in attempting to solve the chemoselectivity issues that plagued cross-benzoin reactions, our group discovered that two aldehydes could be coupled catalytically with N-heterocyclic carbenes (NHCs) when one of the reactants was a protected amino aldehyde. , The reaction generates an α-hydroxy-β-aminoketone [ 3 (Figure )] with good yields and diastereoselectivities. We believed that incorporating a furan ring into this structure would make it more amenable to useful transformations, thereby allowing us to target a variety of natural products. − The high availability and versatility of furans from biomass emphasize the importance of furthering our understanding of these transformations …”