Synthesis of W-Phos Ligand and Its Application in the Copper-Catalyzed Enantioselective Addition of Linear Grignard Reagents to Ketones.

The asymmetric catalytic addition of linear Grignard reagents to ketones has been a long-standing challenge in organic synthesis. Herein, a novel family of PNP ligands (W-Phos) was designed and applied in copper-catalyzed asymmetric addition of linear Grignard reagents to aryl alkyl ketones, allowing facile access to versatile chiral tertiary alcohols in good to high yields with excellent enantioselectivities (up to 94 % yield, 96 % ee). The process can also be used to synthesize chiral allylic tertiary alcohols from more challenging α,β-unsaturated ketones. Notably, the potential utility of this method is demonstrated in the gram-scale synthesis and modification of various densely functionalized medicinally relevant molecules.

Luo W ，Zhang LM ，Zhang ZM ，Zhang J ... -  《-》

Access to chiral α-bromo and α-H-substituted tertiary allylic alcohols via copper(I) catalyzed 1,2-addition of Grignard reagents to enones.

The catalytic asymmetric synthesis of tertiary alcohols by the addition of organometallic reagents to ketones is of central importance in organic chemistry. The resulting quaternary stereocentres are difficult to prepare selectively by other means despite their widespread occurrence in natural products and pharmaceuticals. Here we report on a new methodology which allows access to both α-bromo-substituted and α-H-substituted allylic tertiary alcohols with excellent yields, and enantioselectivities of up to 98% using the copper(I)-catalysed 1,2-addition of Grignard reagents to enones. As an example, the methodology is applied in the synthesis of a chiral dihydrofuran.

Madduri AV ，Minnaard AJ ，Harutyunyan SR 《-》

Copper(I) catalyzed asymmetric 1,2-addition of Grignard reagents to α-methyl substituted α,β-unsaturated ketones.

The first catalytic enantioselective 1,2-addition of Grignard reagents to ketones is presented. This additive-free copper(I) catalyzed 1,2-addition provides chiral allylic tertiary alcohols with an er of up to 98:2 and excellent yields due to the complete shift of overwhelming 1,4-selectivity of copper(I)-catalysts towards 1,2-selectivity in the addition reaction to enones.

Madduri AV ，Minnaard AJ ，Harutyunyan SR 《-》

Asymmetric Direct 1,2-Addition of Aryl Grignard Reagents to Aryl Alkyl Ketones.

Osakama K ，Nakajima M 《-》

Copper-catalyzed asymmetric conjugate addition of Grignard reagents to trisubstituted enones. Construction of all-carbon quaternary chiral centers.

Martin D ，Kehrli S ，d'Augustin M ，Clavier H ，Mauduit M ，Alexakis A ... -  《JOURNAL OF THE AMERICAN CHEMICAL SOCIETY》