A New Method of N‐Benzhydryl Deprotection in 2‐Azetidinone Series.

Abstract

LAURENT, M.; BELMANS, M.; KEMPS, L.; CERESIAT, M.; MARCHAND-BRYNAERT*, J.; Synthesis 2003, 4, 570-576; Unite Chim. Org. Med., Univ. Cathol. Louvain, B-1348 Louvain-la-Neuve, Belg.; Eng.) -C. Herrmann 30-132

Crystal structure of N-[1',1'-(diphenyl)-hydroxymethyl]-3(S)-[1'(R)- hydroxyethyl]-4(S)-(t-butyl-oxomethyl)-azetidin-2-one, C23H27NO4, an unexpectedly stable intermediate in the photochemical cleavage of N-benzhydryl protecting group

“…Our strategy involved the use of a benzhydryl moiety as N-protecting group of the azetidinone ring, instead of the habitual p-anisyl substituent [2] which requires large quantities of ceric ammonium nitrate (CAN), a highly toxic reagent, for deprotection. We found that the benzhydryl group could be readily and quantitatively cleaved by a two-step process as follows [5] 13 C NMR data only [6]. Only 4 structures of azetidin-2-one with the N-hemi-aminal motif have been reported [7][8][9][10]11].…”

“…), we could isolate the titled compound (crude) as a yellowish oil. A typical signal at 87.4 ppm in 13 C NMR spectroscopy indicated the presence of an O,N-hemi-aminal motif (N-C-OH) [6]. The compound was crystallized by slow evaporation from a CH 2Cl2 solution.…”

“…X-ray diffraction analysis of a monocrystal confirmed unambiguously the O,N-hemi-aminal structure of the title compound. This structure was initially proposed on the basis of 1 H and 13 C NMR data only [6]. Only 4 structures of azetidin-2-one with the N-hemi-aminal motif have been reported [7][8][9][10]11].…”

Asymmetric Syntheses of Analogs of Kainic Acid

“…The benzyhryl protecting group is not particularly common, but has found applications in the protection of aziridines [Patwardhan, A. P. et al 2005], azetidines [Laurent, M. et al 2003], in particular β-lactams, and in the selective protection of uracil nitrogens [Wu, F. et al 2004]. Deprotection is typically achieved through catalytic hydrogenation or vigorous acid treatment.…”

“…Deprotection is typically achieved through catalytic hydrogenation or vigorous acid treatment. More novel methods involve oxidation to the benzhydrol either with NBS followed by hydrolysis [Laurent, M. et al 2003] Scheme 38. Application of chiral 1, 1'-binaphtholtitanium complex Another method to induce a high enantioselectivity/diastereoselectivity is the employment of chiral auxiliary.…”