(2-azaallyl)stannanes in synthesis: (1) Formal syntheses of (+/-)-aspidospermidine, (+/-)-aspidospermine, and (+/-)-quebrachamine and (2) Tandem double allylation/ring closing metathesis reactions.
Aponick, Aaron
2003
Abstract
The use of (2-azaallyl)stannanes for the generation 2-azapentadienyl anions for application to the synthesis of alkaloids is described. It was found that stannanes such as <italic>N</italic>-(tri-<italic>n</italic>-butylstannyl)methyl-6-[2-(<italic> tert</italic>-butoxycarbonylamino)-phenyl]-2-[(<italic>E</italic>)-ethylidine]-5-(methoxy)methoxy-6-heptenaldimine, containing tethered aryl-substituted dipolarophiles, failed to undergo the desired intramolecular cycloaddition. Fortunately, after transmetallation, <italic> N</italic>-(tri-<italic>n</italic>-butylstannyl)methyl-2-[(<italic>E</italic>)-ethylidine]-5-(methoxy)methoxy-6-trimethylsilyl-6-heptenaldimine containing a trimethylsilyl-substituted dipolarophile did undergo the desired reaction. In the event, condensation of (tri-<italic>n</italic>-butylstannyl)methylamine with (<italic>E</italic>)-2-[2-(<italic>tert</italic>-Butoxycarbonylamino)-phenyl]-6-formyl-3-(methoxy)methoxy-octa-1,6-diene, intramolecular cycloaddition, and <italic>N</italic>-alkylation of the desired cycloadduct with (<italic>Z</italic>)-3-bromo-1-iodoprop-1-ene proceeded in 59% overall yield. The vinyliodide thus obtained, was then easily transformed in several synthetic steps into (6a<italic>S</italic>*,9a<italic>R</italic>*,9b<italic> R</italic>*)-6a-Ethyldecahydro-pyrrolo[3,2,1-<italic>i,j</italic>]-quinolin-9-one, constituting a formal synthesis of the alkaloids (+/-)-aspidospermidine, (+/-)-aspidospermine, and (+/-)-quebrachamine. A series of simple (2-azaallyl)stannanes were also prepared and their reaction with organometallics studied. It was found that when these stannanes were treated with 2.2 molar equivalents of allylmagnesium bromide, a novel double allylation reaction occurred providing <italic>N,N</italic>-bis-(3-butenyl)amines in 48--91% yield. The reactions could also be quenched with chloroformates to provide the corresponding carbamates in excellent yield. These diene carbamates were transformed in excellent yield into 2,3,6,7-tetrahydroazepines using a ruthenium-catalyzed ring closing metathesis. The use of (2-azaallyl)stannanes as synthons for 2-azaallyl dications, which could also be named amine alpha,alpha<super> '</super>-dications, is described. In addition, preliminary studies on (1) the use of chiral additives to promote asymmetric 2-azaallyl anion cycloaddition reactions; (2) the formation of aniline type chiral atropisomers by the copper-catalyzed <italic> N</italic>-arylation of enantiopure oxazolidinones with <italic>ortho</italic>-substituted aryl halides and (3) the use of 2-amino-1,4-quinones as potential DNA cross-linking agents are described.Subjects
Aspidospermidine+/- Aspidospermine Double Allylation Formal Plusmn Quebrachamine+/- Reactions Ring-closing Metathesis Stannanes-2-azaallyl Syntheses Synthesis Tandem
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