Recent Progress in Selective Additions of Organometal Reagents to Carbonyl Compounds

Abstract

Carbon-carbon bond forming reactions are simple and direct methods for synthesizing the various skeletons and the diverse structures of organic compounds. Even 100 years after the discovery of the Grignard reaction, organomagnesium, organolithium, and organoaluminum remain popular for carbon-carbon bond formation reactions in modern organic chemistry. Moreover, asymmetric alkyl-or aryl-additions to carbonyl compounds with organometal reagents is attractive due to the enantioselective synthesis of chiral secondary alcohols, which sharply contrasts the enantioselective reduction of carbonyl compounds. Herein, we review recent progress in the selective addition to carbonyl compounds with organometal reagents, particularly Li, Mg, and Zn from both a classic viewpoint using metal ate complexes and from a catalytic enantioselective viewpoint using new chiral ligands.

Room temperature and highly enantioselective additions of alkyltitanium reagents to aldehydes catalyzed by a titanium catalyst of (R)‐h8‐binol

“…[1][2][3][4] Over the past two decades, a variety of chiral ligands have been developed to deliver desired alcohols in high enantioselectivities. [5][6][7][8][9][10][11][12][13][14][15][16] Recent studies have shown that organoaluminum compounds are effective reagents, [17][18][19][20][21][22][23][24][25][26][27][28][29] and addition reactions can even be completed in 10 min.…”

“…24 Grignard [30][31][32][33] and lithium 34 reagents have also been established recently as efficient nucleophiles for addition reactions despite their high reactivity. In these studies, a presence of diamine additive and/or excessive amounts of Ti(O-i-Pr) 4 were used to deactivate the high reactivity of the Grignard and lithium reagents. The presence of excess Ti(Oi-Pr) 4 is a general feature of titanium-catalyzed addition reactions for products achieving high enantioselectivities.…”

“…In these studies, a presence of diamine additive and/or excessive amounts of Ti(O-i-Pr) 4 were used to deactivate the high reactivity of the Grignard and lithium reagents. The presence of excess Ti(Oi-Pr) 4 is a general feature of titanium-catalyzed addition reactions for products achieving high enantioselectivities. Mechanistic studies have suggested that the reactions involve an addition of organotitanium compounds, and one of the roles of excess Ti(O-i-Pr) 4 is an in situ generation of the organotitanium reagent via transmetallation of organic nucleophile from organozinc compounds to Ti(O-i-Pr) 4 .…”

“…The presence of excess Ti(Oi-Pr) 4 is a general feature of titanium-catalyzed addition reactions for products achieving high enantioselectivities. Mechanistic studies have suggested that the reactions involve an addition of organotitanium compounds, and one of the roles of excess Ti(O-i-Pr) 4 is an in situ generation of the organotitanium reagent via transmetallation of organic nucleophile from organozinc compounds to Ti(O-i-Pr) 4 . [35][36][37][38][39] However, only a few reports have demonstrated direct asymmetric additions of organotitanium compounds.…”

Different influence of polyoxygenation on the catalytic activity of amido- versus amino-isoborneols

“…[1][2][3][4][5][6][7][8][9][10][11][12] Additionally, the reaction leads to secondary alcohols, which are valuable chiral building blocks 13,14 for the preparation of natural products or new materials with interesting physicochemical properties, 2,9 such as chiral liquid crystals 15 (Scheme 1). Although many chiral ligands for the reaction have been described so far, most of them being N,N-dialkyl amino alcohols (e.g.…”