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Very short highly enantioselective Grignard synthesis of 2,2-disubstituted tetrahydrofurans and tetrahydropyrans.

ABSTRACT: Phenones with elongated chains are shown to be excellent substrates for ligand-promoted asymmetric Grignard synthesis of tertiary alcohols. In turn this enables the simple, short and highly enantioselective (up to 96% ee) preparation of chiral 2,2-disubstituted THFs and THPs. Thus, asymmetric addition of Grignard reagents to ?-chlorobutyrophenones and ?-chlorovalerophenones takes place in the presence of a chiral diaminocyclohexyl-derived tridentate ligand and subsequent base-promoted intramolecular cyclisation occurs with complete retention of asymmetry. As examples of the methodology, we report the shortest syntheses of gossonorol, ?-ethyl-?-phenylbutyrolactone and ?-methyl-?-tolylvalerolactone, the joint-shortest and flexible synthesis of boivinianin A and the shortest formal syntheses of boivinianin B and yingzhaosu C.

SUBMITTER: Monasterolo C

PROVIDER: S-EPMC6611064 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

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Very short highly enantioselective Grignard synthesis of 2,2-disubstituted tetrahydrofurans and tetrahydropyrans.

Monasterolo Claudio C Müller-Bunz Helge H Gilheany Declan G DG

Chemical science 20190527 26

Phenones with elongated chains are shown to be excellent substrates for ligand-promoted asymmetric Grignard synthesis of tertiary alcohols. In turn this enables the simple, short and highly enantioselective (up to 96% <i>ee</i>) preparation of chiral 2,2-disubstituted THFs and THPs. Thus, asymmetric addition of Grignard reagents to γ-chlorobutyrophenones and δ-chlorovalerophenones takes place in the presence of a chiral diaminocyclohexyl-derived tridentate ligand and subsequent base-promoted int ...[more]

PMID: 31341606

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