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Synlett 2016; 27(09): 1339-1343
DOI: 10.1055/s-0035-1561346
letter
© Georg Thieme Verlag Stuttgart · New York

A Concise Enantioselective Synthesis of (+)-L-733,060 and (+)-T-2328 via Sequential Proline Catalysis

Komal G. Lalwani
Chemical Engineering and Process Development Division, National Chemical Laboratory, Pashan Road, Pune 411008, India   Email: a.sudalai@ncl.res.in
,
Arumugam Sudalai*
Chemical Engineering and Process Development Division, National Chemical Laboratory, Pashan Road, Pune 411008, India   Email: a.sudalai@ncl.res.in
› Author Affiliations
Further Information

Publication History

Received: 23 November 2015

Accepted after revision: 11 January 2016

Publication Date:
04 February 2016 (online)

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Abstract

A new, sequential proline-catalyzed approach to the synthesis of (+)-L-733,060 and (+)-T-2328 in high optical purity (93% ee) is described starting from phenyl N-Boc imine. The strategy involves proline-catalyzed Mannich reaction of an arylimine with acetaldehyde followed by α-aminoxylation/Wittig olefination in a sequential fashion as the key steps.

Key words

imine - Mannich reaction - aminoxylation - olefination - sequential

Supporting Information

    Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561346.
  • Supporting Information
 

  • References

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  • 27 (+)-T-2328 Dihydrochloride Salt (3) Yield: 38 mg (quant.); colorless solid; mp 279–281 °C (lit.4a 280–281 °C); [α]D 25 +70.1 (c 0.6, H2O). IR (CHCl3): 680, 889, 1128, 1250, 1370, 1556, 2923, 3350 cm–1. 1H NMR (400 MHz, D2O): δ = 2.07 (s, 2 H), 2.25 (d, J = 7.8 Hz, 1 H), 2.46 (d, J = 14.9 Hz, 1 H), 3.29 (quin, J = 7.3 Hz, 1 H), 3.60 (s, 3 H), 3.66–3.72 (m, 1 H), 4.02 (dd, J = 3.4, 16.1 Hz, 2 H), 4.29 (d, J = 13.2 Hz, 1 H), 4.92 (d, J = 2.9 Hz, 1 H), 7.25 (d, J = 6.6 Hz, 2 H), 7.32 (s, 1 H), 7.44 (d, J = 7.1 Hz, 3 H), 7.49–7.58 (m, 4 H). 13C NMR (100 MHz, D2O): δ = 16.8, 22.7, 43.3, 47.5, 55.3, 55.6, 58.0, 110.9, 111.6, 117.2, 118.4, 119.9 (d, J = 27.0 Hz), 126.2, 126.4, 128.9 (d, J = 3.1 Hz), 129.8, 130.0, 130.4, 131.2, 132.0, 132.6 (d, J = 3.1 Hz), 132.7, 157.4, 157.7 (d, J = 248 Hz). HRMS (ESI): m/z [M + H]+ calcd for C26H27ON3F: 416.2133; found: 416.2114.