Enantiodivergent Formation of C-P Bonds: Synthesis of P-Chiral Phosphines and Methylphosphonate Oligonucleotides

被引：75

作者：

Xu, Dongmin ^{[1
]}

Rivas-Bascon, Nazaret ^{[1
]}

Padial, Natalia M. ^{[1
]}

Knouse, Kyle W. ^{[1
]}

Zheng, Bin ^{[2
]}

Vantourout, Julien C. ^{[1
]}

Schmidt, Michael A. ^{[2
]}

Eastgate, Martin D. ^{[2
]}

Baran, Phil S. ^{[1
]}

机构：

[1] Scripps Res, Dept Chem, La Jolla, CA 92037 USA

[2] Bristol Myers Squibb, Chem Dev, New Brunswick, NJ 08903 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2020年 / 142卷 / 12期

关键词：

EFFICIENT ASYMMETRIC-SYNTHESIS; STEREOSPECIFIC DEOXYGENATION; LIGANDS; OXIDES; STEREOCHEMISTRY; HYDROGENATION; CATALYSIS;

D O I：

10.1021/jacs.9b13898

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Phosphorus Incorporation (PI, abbreviated Pi) reagents for the modular, scalable, and stereospecific synthesis of chiral phosphines and methylphosphonate nucleotides are reported. Synthesized from translimonene oxide, this reagent class displays an unexpected reactivity profile and enables access to chemical space distinct from that of the Phosphorus-Sulfur Incorporation reagents previously disclosed. Here, the adaptable phosphorus(V) scaffold enables sequential addition of carbon nucleophiles to produce a variety of enantiopure C-P building blocks. Addition of three carbon nucleophiles to Pi, followed by stereospecific reduction, affords useful P-chiral phosphines; introduction instead of a single methyl group reveals the first stereospecific synthesis of methylphosphonate oligonucleotide precursors. While both. enantiomers are available, only one isomer is required.the order of nucleophile addition controls the absolute stereochemistry of the final product through a unique enantiodivergent design.

引用

页码：5785 / 5792

页数：8

共 39 条

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