Stephen Christopher Martin Fell

Acetonitrile: an excellent solvent for the 1,1-dichloromethylenation of certain ketones

Abstract Cyclohexanones react rapidly at or below room temperature with Ph 3 P and XCCl 3 (X = Br or Cl) in acetonitrile to give 1,1-dichloromethylene compounds in high yield; some α-methoxyimino β-(1,1-dichloro)methylene esters have been similarly prepared.

Olivanic acid analogues. Part 11. Ozonolysis of α-ethylideneazetidinones: ozonide fragmentation to α-amino acid-N-carboxyanhydrides

Ozonolysis of (E)-7-ethylidene[3-oxa-1-azabicyclo[4.2.0]octane-2-spirocyclohexan]-8-one failed to provide the α-oxoazetidinone 2, but afforded an α-amino acid-N-carboxyanhydride [3,8-dioxa-1-azabicyclo[4.3.0]nonane-2-spirocyclohexane]-7,9-dione 5. [3-Oxa-1-azabicyclo[4.2.0]octane-2-spirocyclohexane]-7,8-dione 2 was instead obtained from the trans-ketone 9 by a sequence involving Baeyer–Villiger oxidation of the azido ketone 10.

2,5-dimethoxy-2,5-dihydrofuran: A convenient synthon for a novel mono-protected glyoxal; synthesis of 4-hydroxybutenolides

Abstract Ozonolysis, followed by a reductive work up of 2,5-dimethoxy-2,5-dihydrofuran generates the symmetrical bis-aldehyde (9) which reacts in situ with certain stabilized phosphoranes. Hydrolysis of the resultant alkene acetals affords 4-hydroxybutenolides (1) end (2).

Synthesis of the 3-acetoxy-7-oxo-1-azabicyclo [3.2.0] hept-2-ene-2-carboxylate system

Abstract Lead tetraacetate oxidation of the carbapenem derived ethanethiol adducts (4–6) gave the corresponding 3-acetoxy-3-ethylthio derivatives (7–9). Oxidation to sulphone and elimination of ethylsulphinic acid furnished the 3-acetoxy-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate ester (12). Alternatively, elimination of acetic acid from (7) and (8) provided a new route to alkylthiocarbapenems.

Olivanic acid analogues. Part 10. X-Ray crystallographic study of the stereochemistry of some 7-heteroatom-substituted 7-acetyl-8-oxo-3-oxa-1-azabicyclo[4.2.0]octane-2-spirocyclohexanes: functional group control of the stereoselectivity of their reduction products using borohydride reagents

(6RS, 7SR)-7-Acetyl-7-azido-8-oxo-3-oxa-1-azabicyclo[4.2.0]octane-2-spirocyclohexane 3 was obtained by reaction of mesyl azide with the trans-ketone 2 in the presence of aqueous base, and the stereochemistry of its major sodium borohydride reduction product, (6RS,7SR,9SR)-7-azido-7-(1-hydroxyethyl)-8-oxo-3-oxa-1-azabicyclo[4.2.0]octane-2-spirocyclohexane 4, was determined by X-ray crystallography. X-Ray studies of the keto sulfide 17 and the chloro ketone 20 confirmed their (6RS,7SR) relative stereochemistry. Reduction of 17 gave the alcohol 18 also with (6RS,7SR,9SR) stereochemistry. In contrast, reduction of 20 with trialkylborohydride reagents gave the (6RS,7SR,9RS)-chloro alcohol 21, and a mechanism is proposed to account for this reversal of C-9 stereoselectivity.

The regioselectivity of cycloaddition reactions between diazomethane and 3-vinylcephalosporins

Diphenylmethyl (6R,7R)-7-phenylacetamido-3-vinylceph-3-em-4-carboxylate 1 undergoes regioselective addition of diazomethane to give the 1-pyrazoline 7, which readily undergoes thermolysis to give the cyclopropyl analogue 10. The regioselectivity is reversed, however, when one or more electron withdrawing ester substituents are attached to the 3-vinyl group.

Olivanic acid analogues. Part 7. Lead tetra-acetate oxidation of 3-alkylthio-7-oxo-1-azabicyclo[3.2.0]heptane-2-carboxylates

Lead tetra-acetate oxidation of alkylthiocarbapenams (2)–(4) gave α-acetoxy sulphides (5)–(7) with inversion of stereochemistry, Iodosobenzene diacetate was also an effective oxidant. Oxidation to sulphone and elimination of alkanesulphinic acid provided the 3-acetoxy-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate system (13). Alternatively, elimination of acetic acid from compounds (5) or (6) with DBU furnished a new route to alkylthiocarbapenems.

Olivanic acid analogues. Part 4. Cycloaddition reactions of p-nitrobenzyl 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate, and synthesis of the 8-oxo-1-azatricyclo[4.2.0.02,4]octane-2-carboxylate system

p-Nitrobenzyl 7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (1) participated in Diels–Alder and 1,3-dipolar cycloaddition reactions, yielding a range of novel polycyclic azetidinone structures. The two 8-oxo-1-azatricyclo [4.2.0.02,4]octane-2-carboxylates (21) and (24) were prepared, and their cyclopropane stereochemistries assigned using nuclear Overhauser difference spectroscopy. Sodium (1′RS,2SR,4RS,6RS,7SR)-7-(1-hydroxyethyl)-8-oxo-l-azatricyclo[4.2.0.0.2,4]octane-2-carboxylate (37) was synthesised from compound (1)via p-nitrobenzyl (1′RS,5RS,6SR)-6-[1-(p-nitrobenzyloxycarbonyloxy)ethyl]-7-oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxylate (32).