Dual stereoselection in the addition of diethylzinc to benzaldehyde by using highly structurally close ligands

Abstract

The screening of the catalytic activity in the diethylzinc reaction of a series of easily accessible (1S)-ketopinic-acid derived hydroxyamides, designed by key structure modifications of a parent highly active related bis(hydroxyamide), has allowed to find the first case of dual stereoselection in highly structurally close ligands of such interesting chemically sustainable typology. The found striking dual stereoselection is explained on the basis of empiric models for the acting zinc catalysts and involved controlling transition states, which are supported by additional specific experimental structure-activity tests.

New advances in dual stereocontrol for asymmetric reactions

“…Recently, a dual stereoselection for the same reaction was reported by De la Moya Cerero and co-workers by using a series of easily accessible (1S)-ketopinic-acid derived hydroxyl amides. 55 The authors explained the striking observed dual stereoselection on the basis of empiric models. The structures for the active zinc catalysts and involved transition states were supported by additional specific experimental structure-activity tests (Scheme 20).…”

EnantioselectiveEthylation of Various Aldehydes Catalyzed by Readily Accessible Chiral Diols

“…1,2 However, much more effort has been devoted towards the synthesis of various chiral secondary alcohols. [3][4][5][6][7][8][9] These alcohols are both key compounds in the preparation of pharmaceuticals and agrochemicals and important intermediates in the synthesis of many substrates such as esters, amides, and ethers. 10 Since the pioneering study of Oguni and Omi, 11 the design and development of selective and efficient ligand structures have been significantly investigated for this useful transformation.…”

“…Among these reactions, the synthesis of optically active pure secondary alcohols via the enantioselective addition of organozinc reagents to aldehydes is a successful method . However, much more effort has been devoted towards the synthesis of various chiral secondary alcohols . These alcohols are both key compounds in the preparation of pharmaceuticals and agrochemicals and important intermediates in the synthesis of many substrates such as esters, amides, and ethers .…”

Enantioselective Addition of Diethylzinc to Aldehydes Catalyzed by Chiral O,N,O‐tridentate Phenol Ligands Derived From Camphor

“…Therefore, the development of efficient methods for the preparation of optically pure secondary alcohols has received much attention, and the asymmetric addition of diethylzinc to aldehydes is one of the most effective approaches for preparing them. 7,8 Although many bidentate chiral ligands have been prepared and tested in the catalytic asymmetric addition of diethylzinc to aldehydes, [9][10][11][12][13][14][15][16][17][18][19][20][21][22][23] the development of efficient tridentate ligands have not been studied extensively. Tridentate ligands should confer more rigidity to the reactive zinc chelate catalyst structures, thereby allowing better discrimination between the two enantiotopic faces of an aldehyde in the transition state complex.…”

“…Although many bidentate chiral ligands have been prepared and tested in the catalytic asymmetric addition of diethylzinc to aldehydes, the development of efficient tridentate ligands have not been studied extensively. Tridentate ligands should confer more rigidity to the reactive zinc chelate catalyst structures, thereby allowing better discrimination between the two enantiotopic faces of an aldehyde in the transition state complex.…”