Development of Ketone-Based Brominating Agents (KBA) for the Practical Asymmetric α-Bromination of Aldehydes Catalyzed by Tritylpyrrolidine

Abstract

Ketone-based brominating agents (KBA), orthosubstituted 2,2,2-tribromoacetophenones, have been developed, and the highly enantioselective and practical α-bromination of aldehydes with KBA was achieved. The reaction could be performed in the presence of only 0.1−1 mol % of catalyst without using a halogenated solvent at 0 °C and was found to be scalable.

Recent Developments in Enantioselective Organocatalytic Cascade Reactions for the Construction of Halogenated Ring Systems

“…Bromination follows the same trend as the other halogenation reactions, in that due to the hazardous nature of elemental bromine, which is a strong irritant, a few practical reagents have been developed as bromine transfer agents that are popular in the laboratory (Figure 62). New ones continue to be developed [146,147] . Nevertheless, in many applications bromine is still used.…”

“…New ones continue to be developed. [146,147] Nevertheless, in many applications bromine is still used.…”

Organocatalytic Enantioselective α-Bromination of Aldehydes with N-Bromosuccinimide

“… 4 − 7 These α-bromination reactions provide highly versatile chiral building blocks that can be rapidly derivatized to α-bromoimines, 8a azidoalcohols, 8b epoxides, 8c or bromohydrins ( Figure 1 ). 4 − 7 …”

“…In 2020, Maruoka and Kano explored alternative aminocatalytic methods using pyrrolidine derivatives instead of 3c as catalyst ( Figure 2 d). 7 They reported the rapid decomposition of NBS ( 2a ) and 4,4-dibromo-2,6-di- tert -butyl-cyclohexa-2,5-dienone ( 2c ) in the presence of pyrrolidine and explored milder brominating agents to avoid the bromination of the pyrrolidine derivatives used as catalysts. They explored several noncommercially available ketone-based brominating agents (KBAs) and chose to use ClPh-KBA 2d ( Figure 2 d).…”

“… 11 Additionally, due to the inherent difficulty of the transformation, the turnover frequencies of their methodologies are generally low, hence requiring either very high catalyst loadings (up to 20 mol %) 4 , 5 or very long reaction times (74 h when using 0.1 mol % of catalyst). 7 Some of the reactions also involve atypical, noncommercially available catalysts and low temperatures (lower than −20 °C). Herein, we describe a method that achieves excellent turnover frequencies and enantioselectivities using NBS and 2 mol % of a Jørgensen–Hayashi type catalyst at convenient temperatures.…”