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

C23H27NO4, monoclinic, P1211 (No. 4), a = 6.356(2) Å, b = 17.418(5) Å, c = 9.586(3) Å, = 100.75(2)°, V = 1042.6 Å, Z = 2, Rgt(F) = 0.055, wRref(F) = 0.153, T = 293 K. Source of material Starting from N-(diphenyl-methyl)-3(S)-[1 (R)-hydroxyethyl]4(S)-(t-butyl-oxomethyl)-azetidin-2-one [3], after treatment at 293 K with N-bromosuccinimide (1.2 equiv.) in CH2Cl2-H2O mixture (5:1) under irradiation (white light) in the presence of a catalytic amount of molecular bromine (0.1 equiv.), we could isolate the titled compound (crude) as a yellowish oil. A typical signal at 87.4 ppm in 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 CH2Cl2 solution. Experimental details All the H atoms of the CH2, CH3 and aromatic groups were calculated. Those of the CH and OH were located by difference Fourier maps. The H atoms were refined with a common isotropic temperature factor (Uiso = 0.120(4) Å). Discussion Chiral functionalized azetidinones ( -lactams) are valuable key-intermediates in organic synthesis for the preparation of various biologically active compounds [1], particularly in the field of antibiotics related to the large family of penicillins [2]. Recently, we became interested in the synthesis of novel precursors of carbapenems [3, 4]. 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]: (i) photoactivated bromination and in situ hydrolysis of the resulting N-(1,1-diphenyl)-bromomethyl residue into N-(1,1-diphenyl)-hydroxymethyl residue; (ii) acid-catalyzed decomposition of the hemi-aminal intermediate into NH-azetidinone and benzophenone. Usually, hemi-acetal and hemiaminal compounds are unstable, and rapidly decompose to regenerate their carbonyl precursors. However, N-[1 ,1 -(diphenyl)hydroxymethyl]-3(S)-[1 (R)-hydroxyethyl]-4(S)-(t-butyl-oxomethyl)-azetidin-2-one was surprisingly stable and required the addition of a strong acid (p-Tos-OH, 1 equiv.) to release benzophenone. 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 H and C NMR data only [6]. Only 4 structures of azetidin-2-one with the N-hemi-aminal motif have been reported [7-10,11]. In all these molecules the C—N (mean value 1.432 Å) and C—OH (mean value 1.390 Å) bond lengths are shorter than those observed in the title compound, 1.472(5) Å and 1.418(5) Å respectively. This is probably the result of the steric constraint on the C atom resulting from the substitution by two phenyl rings. There are two intermolecular hydrogen bonds with the following geometry: O7–H7···O5(1+x, y, z): d(O—H) = 0.86 Å; d(H···O) = 2.13 Å; d(O···O) = 2.959 Å; O–H···O = 161°. O16–H16···O7(x–1, y, z): d(O—H) = 1.19 Å; d(H···O) = 1.98 Å; d(O···O) = 2.998 Å; O–H···O = 140°. A slight intramolecular interaction is also observed between the OH and the C=O of the N-hemi-aminal group: O16–H16···O5: O16-H16 = 1.19 Å; H···O = 2.54 Å; O···O = 3.510 Å and O-H···O = 137°. This is rather curious as a nice intramolecular H bond involving this hydroxyl and the other carbonyl oxygen (O10) would be possible (d(O16···O10) = 2.91 Å but H16 is not properly oriented (d(H16···O10) = 3.19 Å). Z. Kristallogr. NCS 218 (2003) 145–147 145 © by Oldenbourg Wissenschaftsverlag, München