Tandem ireland-claisen rearrangement ring-closing alkene metathesis in the construction of bicyclic beta-lactam carboxylic esters.
4-Alkenyl-2-azetidinone systems were converted to the corresponding ethyl 2-¿4-alkenyl-2-oxo-1-azetidinyl-4-pentenoates. In addition, 4-(2-propenyl-1-oxy)-, 4-(2-propenyl-1-thio)-, 4-¿N-(2-propenyl)-(4-toluenesulfonyl)- and (3S, 4R)-4-(2-propenyl)-3-¿(1R)-1-(tert-butyldimethylsilyloxy)ethyl-++ +azeti din-2-one were converted into beta-lactam dienes via sequential N-alkylation, Ireland-Claisen ester enolate rearrangement and esterification. Ring-closing metathesis using the Schrock ¿(CF(3))(2)MeCO(2)Mo(=CHCMe(2)Ph)(=NC(6)H(3)-2,6-iso-Pr(2)) (1) or Grubbs Cl(2)(Cy(3)P)(2)Ru=CHPh (2) carbenes gave a series of ¿5.2.0 and ¿6.2.0 bicycles. Subsequent elaboration of the analogous (2R,7R, 8S)-tert-butyl 8-¿(1R)-(tert-butyldimethylsilyloxy)ethyl-1-aza-9-oxobicyclo++ +¿5.2. 0non-4-ene-2-carboxylate (15), via selenation and desilylation, gave (+)-(2S,7R,8S)-tert-butyl 8-¿(1R)-hydroxyethyl-1-aza-9-oxobicyclo¿5.2.0nona-2, 4-diene-2-carboxylate (18), a novel type of bicyclic beta-lactam. Diels-Alder cycloaddition further afforded tetracyclic systems exemplified by tert-butyl (1R,4S,5R,7S)-4-¿(1R)-1-hydroxyethyl-3,9, 11-trioxo-10-phenyl-2,8,10,12-tetraazatetracyclo¿5.5.2.0.(2, 5)0(8, 12)tetradec-13-ene-1-carboxylate (19).
Barrett
A G
AG
Department of Chemistry, Imperial College of Science, Technology and Medicine, South Kensington, London, UK SW7 2AY.
Ahmed
M
M
Baker
S P
SP
Baugh
S P
SP
Braddock
D C
DC
Procopiou
P A
PA
White
A J
AJ
Williams
D J
DJ
D000475:Alkenes; D002264:Carboxylic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D002625:Chemistry, Organic / Q000379:methods; D004952:Esters / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D015394:Molecular Structure; D047090:beta-Lactams / Q000138:chemical synthesis* / Q000737:chemistry
D000475:Alkenes; D002264:Carboxylic Acids; D004952:Esters; D047090:beta-Lactams