D. Ivor John

Stereoselective preparation of 6β -substituted penicillanates : Tri-organotin hydride reduction of 6-isocyano-,6-phenylselenenyl-, 6-halo-, and 6-isothiocyanato-penicillanates

Abstract 6β-Benzyl-, 6β-(2-hydroxyprop-2-yl)-, 6β-methoxycarbonylmethyl-, 6β-methoxycarbonylethyl-, 6β-(t-butoxycarbonylmethyl)-, and 6β-methylthiopenicillanates 10 – 15 have been prepared stereo-selectively by tri-n-butyltin hydride reduction of the corresponding 6β-isocyanopenicillanates 4 – 9 A minor side-product (15%) isolated from the reduction of benzyl 6α-(2-hydroxyprop-2-yl)-6β-isocyanopenicillanate 5 was identified as (1R, 5R)-6-[(1R)-1-benzyloxycarbonyl-2-methylprop-1-yl]-1-(2-hydroxyprop-2-yl) -2,6-diaza-4-thiabicyclo [3,2,0]hept-2-en-7-one 18 , and small quantities of analogous thiazolines 19 and 20 were detected in the crude mixtures from the reductions of the 6α-benzyl- and 6α-methoxycarbonylmethyl-6β-isocyanopenicillanates 4 and 6 . Benzyl and methyl penicillanates 30 and 31 were obtained by tri-n-butyltin hydnde reduction of the 6α-bromopenicillanates 28 and 29 , and reduction of benzyl 6,6-dibromopeniciallanate 35 gave a mixture of products in which the 6β-bromopenicillanate 37 predominated. 6β-Chloro-, 6β-phenylselenenyl-, and 6β-allylpenicillanates 48 , 49 and 52 were obtained by tri-n-butyltin hydride reduction of the corresponding 6-phenyl- selenenylpenicillanates 43, 45, 50 and 51 . In contrast, tri-organotin hydride reduction of methyl 6α-isothiocyanatopenicillanate 53 was accompanied by sulphur-C(2) bond cleavage to give rearranged thiazoline-azetidinones 54 and 55

Preparation of 6α-monosubstituted and 6,6-disubstituted penicillanates from 6-diazopenicillanates: reactions of 6-diazopenicillanates with alcohols, thiols, phenylseleninyl compounds, and allylic sulphides, and their analogues

Reactions of 6-diazopenicillanates (1) and (2) with a range of compounds, in some cases catalysed by BF3–Et2O or Cu(acac)2, have been investigated, and found to be useful for the synthesis of 6α-monosubstituted and 6,6-disubstituted penicillanates. Thus the 6α-alkoxy- and 6α-alkylthio-penicillanates (7)–(15), the 6-phenylselenopenicillanates (26)–(32), and the 6-allyl-6-alkylthio- and 6-ally-6-phenylseleno-penicillanates (39)–(46), were obtained from reactions between 6-diazopenicillanates (1) and (2) and alcohols, thiols, phenylselenol, diphenyl diselenide, phenylseleninyl chloride, allylic sulphides, and allylic selenides. Reactions between 6-diazopenicillanates (1) and (2) and carboxylic acid derivatives and ethers were also briefly examined.The structure of 2,2,2-trichioroethyl 6α-allyl-6β-phenylthiopenicillanate (39) was confirmed by a single-crystal X-ray study.

Boron trifluoride catalysed reactions of 2,2,2-trichloroethyl 6-diazopenicillanate with aromatic aldehydes: rearrangements via penam c(5)-c(6) bond cleavage.

Abstract The BF3·Et2O catalysed reactions of diazopenicillanate 1 with aromatic aldehydes provide 2,3-dihydrothiazolo[2,3-b][1,3]oxazin-5-ones 4 via C(5)-C(6) cleavage of 6-formyl-penicillanates 8.

Triorganotin hydride reduction of 6β-isothiocyanatopenicillanates: a radical-induced sulphur–C(2) bond cleavage

Triorganotin hydride reduction of methyl 6β-isothiocyanatopenicillanate is accompanied by intra-molecular radical capture and cleavage of the sulphur–C(2) bond to give thiazolines (9) and (10); a similar mechanism is proposed for the formation of thiazoline (3), a minor product of tri-n-butyltin hydride reduction of benzyl 6α-(1-hydroxyl-1-methylethyl)-6β-isocyanopenicillanate (1; R2= Me2COH).

Reduction of 6α-alkyl-6β-isocyanopenicillanates by tri-n-butyltin hydride. A stereoselective synthesis of 6β-alkylpenicillanates

Summary 6β-Benzyl-, 6β-(1-hydroxy-1-methylethyl)-, 6β-methoxycarbonylmethyl-, and 6β-(2-methoxycarbonylethyl)-penicillanates (5)–(8) have been prepared stereoselectively, and in good yield, by tri-n-butyltin hydride reduction of the corresponding 6α-alkyl-6β-isocyanopenicillanates (1)–(4); similarly 6,6-dibromopenicillanate (12) has been reduced to give a mixture of 6β- and 6α-bromopenicillanates (13) and (14) in the ratio of 85 : 15, respectively.

Reactions of benzyl 6-lsocyanopenicellanate with thiocarbonyl reagents. Novel rearrangements to 2,3-dihydrothiazolo [2,3-b][1,3]-thiazin -5-ones via penam C(5)–C(6) bond cleavage. X-Ray crystal structure and absolute configuration of two rearrangement products

Base-promoted reactions of benzyl 6-isocyanopenicillanate with CS2, with CS2–Mel, and with PhNCS, Proceed via C(5)–C(6) bond cleavage to give pairs of diastereoisomers; the structures of two of these diastereoisomers were established by X-ray crystallography.

Aspects of the chemistry of 6-diazopenicillanate S-oxide and S,S-dioxide

Procedures are developed for the preparation of 6-diazopenicillanate S-oxides and S,S-dioxides from the corresponding 6-phenylacetamidopenicillanates by N-nitrosation and thermal decomposition of the intermediate N-nitroso amides. The chemistry of these 6-diazopenicillanate S-oxides and S,S-dioxides was then briefly investigated, their reactions with pseudohalogens, alcohols, thiols, phenylseleno compounds, and aromatic aldehydes being examined. In some cases the products from these reactions were rearranged into the corresponding cepham or cephem derivatives.

Synthesis of penicillanate dimers: an X-ray crystal structure of a penicillanylidene-penicillanate

On treatment with copper bis(acetoacetonate) in dichloromethane, 2,2,2-trichloroethyl 6-diazopenicillanate (1), and its (1S)-S-oxide and S,S-dioxide (2) and (3), were found to lose nitrogen and dimerize to give mixtures of (E)- and (Z)- alkenes (5)–(10), in which the (E)-isomers (5)–(7) predominated. The structure of the minor dimer from the 6-diazopenicillanate (1) was established as (8) by X-ray crystallography.

Some Lewis acid-catalysed reactions between 2,2,2-trichloroethyl 6-diazopenicillanate and ketones

In the presence of boron trifluoride–diethyl ether, 6-diazopenicillanate (1) and acetone, cyclopentanone, and acetophenone, gave mixtures of 6α-alkyl-6β-acylpenicillanates and thiazolo-oxazinones, which had been formed via C(5)–C(6) bond cleavage.

The formation and X-ray crystal structures of novel spiro-aziridine-azetidinones from thermal reactions between 6-diazopenicillanates and aromatic imines

The spiro-aziridine-azetidinones (8), (9), (12)–(17) were prepared by heating equimolar amounts of 6-diazopenicillanate (1) and aromatic imines under reflux in chloroform; the structures of the analogues (18) and (19), prepared from cinnamylidene p-methoxyaniline, were established by X-ray diffraction, as was the structure of the monocyclic β-lactams (10) and (11) formed by heating the benzylidene aniline adducts (8) and (9) under reflux in toluene.