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An umpolung-enabled copper-catalysed regioselective hydroamination approach to α-amino acids.

ABSTRACT: A copper-catalysed regio- and stereoselective hydroamination of acrylates with hydrosilanes and hydroxylamines has been developed to afford the corresponding α-amino acids in good yields. The key to regioselectivity control is the use of hydroxylamine as an umpolung, electrophilic amination reagent. Additionally, a judicious choice of conditions involving the CsOPiv base and DTBM-dppbz ligand of remote steric hindrance enables the otherwise challenging C-N bond formation at the α position to the carbonyl. The point chirality at the β-position is successfully controlled by the Xyl-BINAP or DTBM-SEGPHOS chiral ligand with similarly remote steric bulkiness. The combination with the chiral auxiliary, (-)-8-phenylmenthol, also induces stereoselectivity at the α-position to form the optically active unnatural α-amino acids with two adjacent stereocentres.

SUBMITTER: Nishino S

PROVIDER: S-EPMC8409476 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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An umpolung-enabled copper-catalysed regioselective hydroamination approach to α-amino acids.

Nishino Soshi S Miura Masahiro M Hirano Koji K

Chemical science 20210727 34

A copper-catalysed regio- and stereoselective hydroamination of acrylates with hydrosilanes and hydroxylamines has been developed to afford the corresponding α-amino acids in good yields. The key to regioselectivity control is the use of hydroxylamine as an umpolung, electrophilic amination reagent. Additionally, a judicious choice of conditions involving the CsOPiv base and DTBM-dppbz ligand of remote steric hindrance enables the otherwise challenging C-N bond formation at the α position to the ...[more]

PMID: 34567503

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