1β-Methylcarbapenem intermediates via the thiolysis of a Meldrum's precursor

Jacopin, Christophe; Laurent, Mathieu Y.; Belmans, Marc; Kemps, Luc; Cérésiat, Marcel; Marchand‐Brynaert, Jacqueline

doi:10.1016/s0040-4020(01)01082-1

Cited by 4 publications

(2 citation statements)

References 29 publications

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“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Tinant¹,

Laurent²,

Cérésiat³

et al. 2003

Zeitschrift Für Kristallographie - New Crystal Structures

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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 CH 2Cl2-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 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. Experimental detailsAll the H atoms of the CH 2, 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 (U iso = 0.120(4) Å 2 ). Discussion -[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 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]. 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

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Section: Discussionmentioning

confidence: 99%

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

Tinant¹,

Laurent²,

Cérésiat³

et al. 2003

Zeitschrift Für Kristallographie - New Crystal Structures

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“…Accordingly, 13 could be engaged in the further synthesis of carbapenems 1 , instead of intermediate 2 . This possibility has been experimentally confirmed by reacting 13 with the Meldrum ester of 2-methylmalonic acid ( 14 ) to furnish the known azetidinone 15 (Scheme ) 6 Following Steps To Obtain 2 a a Reagents and conditions: (i) TBDMSCl, imidazole, DMF, rt, 95%; (ii) NaOAc, 18-c-6, AcOH, rt, 17 h, 68% conversion; (iii) Et 3 N, AcOEt, 70 °C, 5 h, 66% conversion. …”

mentioning

confidence: 96%

Regioselective Baeyer−Villiger Oxidation in 4-Carbonyl-2-azetidinone Series: A Revisited Route toward Carbapenem Precursor

2004

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A novel synthesis of acetoxyazetidinone 2 is presented. The azetidinone ring of compounds 7 is formed by C-3/C-4 cyclization of (2R,3R)-epoxybutyramide precursors 6, N-protected with a benzhydryl group. N-Deprotection by photoactivated bromination and acidic treatment leads to compounds 10 with various CO-R substituents at C-4. Transformation of these substituents by Baeyer-Villiger oxidation gives the desired regioisomer 11 with the cyclopropyl side-group which is the only group (among R = H, Ph, t-Bu, i-Pr, c-Pr) able to satisfy both the steric requirements of the cyclization step and the electronic requirements of the oxidative rearrangement step.

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Synthesis of Bis‐spiro Cyclopropanes Based on Meldrum’s Acid by Milling

Kashani

Pesyan

Tunç

et al. 2015

J Chinese Chemical Soc

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Reaction of 2,2-dimethyl-1,3-dioxane-4,6-dione (Meldrum's acid) with various solid aldehydes in the presence of cyanogen bromide and solid sodium ethoxide (EtONa) leads to the selective and efficient formation of bis-spiro cyclopropanes based on Meldrum's acid at the range of 0°C to room temperature. The products were obtained in good to excellent yields. Structure elucidation is carried out by 1 H NMR, 13 C NMR, FT-IR spectroscopy, mass analyses and X-ray crystallography techniques. A possible mechanism for the formation of products is also discussed under solvent-free condition.

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1β-Methylcarbapenem intermediates via the thiolysis of a Meldrum's precursor

Cited by 4 publications

References 29 publications

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

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

Regioselective Baeyer−Villiger Oxidation in 4-Carbonyl-2-azetidinone Series: A Revisited Route toward Carbapenem Precursor

Synthesis of Bis‐spiro Cyclopropanes Based on Meldrum’s Acid by Milling

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