An approach toward isoindolobenzazepines using the ammonium ylide/Stevens.
Ammonium ylides derived from the Cu(II)-catalyzed decomposition of alpha-diazo carbonyls tethered to tertiary amines underwent a benzylic Stevens [1,2]-rearrangement to give tetrahydroisoquinolines or benzazepines containing fused five-membered rings, a feature found in the cephalotaxus alkaloids. Model studies were also carried out toward the synthesis of lennoxamine, a member of the isoindolobenzazepine family of alkaloids. The approach utilized is based on the Rh(II)-catalyzed reaction of an alpha-diazo carbonyl compound containing an amido group in the gamma-position. Treatment of several N,N-dialkyl-substituted amido diazo-esters with Rh2(OAc)4 in benzene at 80 degrees C in the presence of several dienophiles gave [4 + 2]-cycloadducts derived from the Diels-Alder reaction of a transient alpha-amino isobenzofuran intermediate. In the absence of an external trapping agent, no rearranged product derived from an ammonium ylide intermediate could be detected in the crude reaction mixture. In contrast to this result, reaction of the related diazo dihydroisoquinoline amide 46 with Rh2(OAc)4 afforded the isoindolobenzazepine ring system in high yield. Formation of the 5,7-fused skeleton was rationalized in terms of a spirocyclic ammonium ylide that underwent a preferential Stevens [1,2]-shift of the benzylic carbon atom. While we were ultimately thwarted in using the ammonium ylide/rearrangement cascade for a lennoxamine synthesis by an uncooperative diazo transfer reaction, the cascade sequence was shown to be useful for the preparation of various isoindolobenzazepines.
Department of Chemistry, Emory University, Atlanta, Georgia 30322, USA. chemap@emory.edu
A
A
Padwa
L S
LS
Beall
C K
CK
Eidell
K J
KJ
Worsencroft
D000470:Alkaloids / Q000138:chemical synthesis; D001552:Benzazepines / Q000138:chemical synthesis*; D007211:Indoles / Q000138:chemical synthesis*; D009942:Organometallic Compounds / Q000737:chemistry; D000644:Quaternary Ammonium Compounds / Q000737:chemistry
D000470:Alkaloids; D001552:Benzazepines; D007211:Indoles; D009942:Organometallic Compounds; D000644:Quaternary Ammonium Compounds; C062962:dirhodium tetraacetate