Synthesis 2002(7): 0945-0950
DOI: 10.1055/s-2002-28503
SPECIALTOPIC
© Georg Thieme Verlag Stuttgart · New York

Indium-Induced Addition of Bromomethylacrylates to Phthaloyl-Protected Amino Aldehydes

Steffen Steurer, Joachim Podlech*
Institut für Organische Chemie der Universität Stuttgart, Pfaffenwaldring 55, 70569 Stuttgart, Germany
Fax: +49(711)6854269; e-Mail: joachim.podlech@po.uni-stuttgart.de;
Further Information

Publication History

Received 3 March 2002
Publication Date:
14 May 2002 (online)

Abstract

The indium-mediated reaction of phthaloyl-protected α-amino aldehydes 1-4 with methyl 2-(bromomethyl)acrylate in aqueous solvents was investigated. The homoallyl alcohols 5-8 were formed in 72-89% yields, the anti-isomers being the major diastereoisomers (dr 45:55-18:82). Acid-catalyzed esterification (H2SO4 in Et2O) led to α-methylene γ-butyrolactones 9,10 with yields ranging from 88 to 99%. Conjugate addition of cyanide and thiophenolate led to the addition products with improved selectivities compared with additions to carbamate-protected substrates. During the conjugate addition of a cuprate, a trapping of the intermediate enolate by a phthaloyl carbonyl group occurred, leading to tetracycle 11 in 57% yield. The configuration of all diastereo­isomers could be established by three X-ray crystallographic analyses and by NMR spectroscopy.

11

The respective isomers could be separated by medium pressure liquid chromatography (MPLC). All new compounds gave satisfactory spectroscopic data (NMR, IR, MS, [α]D 20 and elemental analyses).

13

Crystal data for 11a: C24H35NO4Si, M = 429.62 g/mol, orthorhombic, space group P212121. a = 10.009(2), b = 12.223(2), c = 20.057(3) Å, V = 2453.8(7) Å3, Z = 4, Dc = 1.163 Mg/m3, µ (Mo-Kα) = 0.123 mm-1, F(000) = 928. Data (2735 collected reflections, and 2063 unique reflections [I > 2σ(I)]) were measured on a Nicolet P3 diffractometer with Mo-Kα radiation (graphite monochromator) using 2θ-ω-scans at 293(2) K. The structure was solved by direct methods and the non-hydrogen atoms were refined anisotropically by full-matrix least-squares based on F2 to give the agreement factors R1 = 0.0597, ωR2 = 0.1289. Computations were carried out using the SHELXTLTM program. Crystallographic data have been deposited at the Cambridge Crystallographic Data Centre as supplementary publication no. CCDC-179132 (8a), CCDC-179133 (9a), and CCDC-179131 (11a). Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, (UK), fax:+44(1223)336033 or email: deposit@ccdc.cam.ac.uk.