Chromium Carbene Complexes of Diterpenoids: Synthesis and Reactivity

Abstract

Aminocarbenes derived from some benzenes and diterpenoids have been synthesised in high yield from alkoxycarbene and amide precursors. Insertion reactions of electron-deficient alkenes with aminocarbenes generally gave aryl ketone products derived from aminocyclopropane ring opening and subsequent enamine hydrolysis. Reaction conditions for the insertion were optimised by varying the amino substituent on the carbene, morpholino substituted aminocarbenes giving the highest yields. Alkenylsulfones gave products derived from insertion of the carbene into the β-CH bond of the alkene, while propenoic acid, propenal or nitroethene gave formyl derivatives. The reaction of aminocarbenes with electron-rich alkenes failed to give insertion products. Reaction of alkynes with ring A modified diterpenoid aminocarbenes gave androstane analogues. The yield of the cyclopentaannulated product was dependent on the alkynyl substituents, heteroatom moieties giving low or zero yield. The reaction was optimised by reaction of 1-heptyne with six different amino-substituted carbenes, the morpholino derivative again giving the highest yields. An attempt to impose asymmetric induction in the cyclopentaannulation by using a C2-symmetric amino-substituted carbene gave a mixture (1:1) of the epimeric steroidal derivatives. Reaction of diterpenoid alkoxy- or thio-carbenes with ethynylferrocene afforded ferrrocenylchrysene-1,4-dione derivatives. 2-Alkynylanilines were synthesised in high yield using palladium mediated coupling of 2-iodoaniline with some monosubstituted alkynes. Reaction of these 2-alkynylanilines with a diterpenoid acyloxycarbene gave diterpenoid-tethered alkynylaminocarbenes. Thermolysis of the tethered alkynylaminocarbenes gave indole derivatives. Photolysis of diterpenoid alkoxycarbenes bearing an ortho methoxy group with N-methylbenzylideneimine failed to give β-lactam products, leading instead to decarbonylation and internal ligation of the ortho methoxy group to chromium. The ortho oxygen-containing substituent was removed by palladium-mediated reductive cleavage of the corresponding triflate prior to carbene formation, a range of conditions being investigated in order to avoid concomitant displacement of the aryl bromide. Photolysis of both-benzene derived and 12-desoxyditerpenoid thio-, amino- and alkoxy-carbenes with N-methylbenzylideneimine gave β-lactams.