Catalytic enantioselective arylations: boron to zinc exchange as a powerful tool for the generation of transferable aryl groups

Abstract

A transmetalação entre boro e zinco apresenta uma grande importância para diversas aplicações em síntese orgânica, uma vez que permite a formação de novas ligações carbono-carbono entre reagentes organometálicos e espécies eletrofílicas. A arilação direta de aldeídos e, mais raramente de cetonas, de maneira catalítica e enantiosseletiva, empregando catalisadores quirais, têm sido descrita recentemente. Os diaril metanóis opticamente enriquecidos, obtidos nessas reações são precursores valiosos para a síntese de moléculas bioativas. O presente trabalho apresenta uma revisão sobre essa crescente área de atuação e destaca alguns dos desafios que ainda permanecem.The transmetalation between boron and zinc is of great importance for application in organic synthesis, since it allows the formation of new carbon-carbon bonds between organometallic units and electrophiles. The direct arylation of aldehydes or more scarcely ketones, in a catalytic, enantioselective manner using chiral catalysts has been described recently. The enantiomerically enriched diarylmethanols obtained in these reactions are valuable precursors for important bioactive molecules. This review provides a synopsis of this ever-growing field and highlights some of the challenges that still remain.

Diastereoselective addition of arylzinc reagents to a sugar aldehyde. Formal synthesis of (+)-7-epi-goniofufurone

“…1 After optimization of the reaction conditions in order to achieve high yields and diastereoselectivity, we found that conducting the reaction in toluene, at 60 o C furnished the best results. Next, the scope of the arylation of the chiral furanoside aldehyde 1 with different arylzinc reagents was examined and in all cases studied, good yields and d.r.…”

The inexpensive additive N‐methylmorpholine effectively decreases the equivalents of nucleophiles in the catalytic highly enantioselective arylation of aryl aldehydes

“…An increase of the catalyst loading did not further raise the enantioselectivity (entries 2 and 6). The decrease and increase of titanium tetrapropoxide both slightly reduced enantioselectivity to 94% and 93%, respectively (entries 2,7,8). For the loading of NMM, 1.6 mmol NMM was ideal in view of the 95% ee (entries 2, 9, 10).…”

“…Enantiopure diarylmethanols are important structural scaffolds in the synthesis of pharmaceuticals and bioactive compounds. [1][2][3][4][5][6][7][8] Accordingly, the catalytic asymmetric addition of arylmetal reagents and aryl boronic acids to aldehydes has attracted considerable attention over the past decades. [9][10][11][12][13][14][15][16][17] Since Fu and coworkers seminally reported the asymmetric addition with Ph 2 Zn, 18 arylzinc reagents from various aryl sources such as arylboronic acids have been commonly explored for the enantioselective synthesis of diarylmethanols.…”

Catálise assimétrica no Brasil: desenvolvimento e potencialidades para o avanço da indústria química brasileira

“…Com esse ligante, uma série de diarilmetanóis foi preparada com altos rendimentos e excessos enantioméricos de até 96%. 45 Os diarilmetanóis quirais obtidos são valiosos precursores para a síntese de compostos biológica e farmacologicamente importantes, 46 tais como a orfenadrina e a neobenodina, que apresentam atividade anti-histamínica e anti-colinérgica (Esquema 12). 47 Já a carbinoxamina é um antagonista histamínico H 1 , usado no tratamento de doenças alérgicas, assim como o cloridrato de cetirizina que é extremamente seletivo para receptores do tipo H 1 e já é comercializado na sua forma enantiomericamente pura (S) desde 2002.…”