Department of Chemistry, Scripps Research, 10550 North Torrey Pines Road, La Jolla, California 92037, United States.
Chemistry Development, Bristol-Myers Squibb, One Squibb Drive, New Brunswick, New Jersey 08903, United States.
J Am Chem Soc. 2020 Mar 25;142(12):5785-5792. doi: 10.1021/jacs.9b13898. Epub 2020 Mar 16.
Phosphorus Incorporation (PI, abbreviated Π) reagents for the modular, scalable, and stereospecific synthesis of chiral phosphines and methylphosphonate nucleotides are reported. Synthesized from limonene 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 Π, 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 Π 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.
报道了用于手性膦和甲基膦酸核苷酸的模块化、可扩展和立体特异性合成的磷整合（PI）试剂。该试剂类由氧化柠檬烯合成，具有出乎意料的反应性，并能够获得与先前公开的磷-硫整合试剂不同的化学空间。在这里，适应性强的磷（V）支架能够连续添加碳亲核试剂，从而生成各种对映纯的 C-P 构建块。向 Π 添加三个碳亲核试剂，然后进行立体特异性还原，可得到有用的 P-手性膦；引入单个甲基取代基则揭示了第一个立体特异性合成的甲基膦酸寡核苷酸前体。虽然两种 Π 对映异构体都可用，但仅需要一种异构体——亲核试剂的添加顺序通过独特的对映体发散设计控制最终产物的绝对立体化学。
