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I'd like to deprotect a benzyl group for a Fráter–Seebach alkylation. Would it be possible to do this with a Birch reduction using Li/NH3 (or Na/NH3), without also reducing the ester carbonyl group?

Selective debenzylation of methyl (S)-3-(benzyloxy)butanoate

If not, hydrogenation over Pd/C seems to be a plausible alternative. How else can I remove the benzyl group on oxygen?

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In Wutz's book on protecting groups,[1] I found an example of almost instantaneous reductive debenzylation which leaves an ester untouched:[2]

Debenzylation example with Na/NH3

The use of BCl3 is also possible:[3]

Debenzylation with BCl3


References:

  1. Wuts, P. G. M. Greene's Protective Groups in Organic Synthesis, 5th ed.; Wiley: Hoboken, NJ, 2014, p 131.

  2. Sulikowski, M. M.; Davies, G. E. R. E.; Smith, A. B., III. Avermectin–milbemycin synthetic studies. Part 7. An approach to the southern hemisphere of milbemycin α1. J. Chem. Soc., Perkin Trans. 1 1992, 979–989. DOI: 10.1039/P19920000979.

  3. Williams, D. R.; Brown, D. L.; Benbow, J. W. Studies of Stemona alkaloids. Total synthesis of (+)-croomine. J. Am. Chem. Soc. 1989, 111 (5), 1923–1925. DOI: 10.1021/ja00187a081.

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