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Enantioselective synthesis of (R)-tolterodine using lithiation/borylation-protodeboronation methodology.

ABSTRACT: The synthesis of the pharmaceutical (R)-tolterodine is reported using lithiation/borylation-protodeboronation of a homoallyl carbamate as the key step. This step was tested with two permutations: an electron-neutral aryl Li-carbamate reacting with an electron-rich boronic ester and an electron-rich aryl Li-carbamate reacting with an electron-neutral boronic ester. It was found that the latter arrangement was considerably better than the former. Further improvements were achieved using magnesium bromide in methanol leading to a process that gave high yield and high enantioselectivity in the lithiation/borylation reaction. The key step was used in an efficient synthesis of (R)-tolterodine in a total of eight steps in a 30% overall yield and 90% ee.

SUBMITTER: Roesner S

PROVIDER: S-EPMC3672952 | biostudies-literature | 2012 Nov

REPOSITORIES: biostudies-literature

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Enantioselective synthesis of (<i>R</i>)-tolterodine using lithiation/borylation-protodeboronation methodology.

Roesner Stefan S Aggarwal Varinder K VK

Canadian journal of chemistry 20121101 11

The synthesis of the pharmaceutical (<i>R</i>)-tolterodine is reported using lithiation/borylation-protodeboronation of a homoallyl carbamate as the key step. This step was tested with two permutations: an electron-neutral aryl Li-carbamate reacting with an electron-rich boronic ester and an electron-rich aryl Li-carbamate reacting with an electron-neutral boronic ester. It was found that the latter arrangement was considerably better than the former. Further improvements were achieved using mag ...[more]

PMID: 23750041

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