Synthesis of Diversely Functionalized Hexa­­-hydropyrrolo[2,3-b]indoles

functionalized indoles - reductive cyclization - Claisen rearrangement

Significance

The synthesis of hexahydropyrrolo[2,3-b]indoles from indolin-3-ones which incorporates a three-step domino sequence is reported. The sequence is a new, general, and reason­-ably efficient (48-88%) synthesis which allows introduction of elements of diversity at the quaternary carbon site of the pyrrolo[2,3-b]indole ring system.

Comment

The hexahydropyrrolo[2,3-b]indole ring containing a 3a-allyl substituent is a widely distributed structural motif present in a number of biologically active alkaloids. Previous routes to such systems have involved alkylation of indoles and indole-2-ones, direct substitution of 3a-phenylselenyl- or 3a-bromo-pyrrolo[2,3-b]indoles with allyl tributylstannanes, among others. The current route is a generalization of a synthesis previously disclosed in communication form. The advantage of Wittig olefination is to induce, by double bond isomerization, a Claisen rearrangement which, in addition to the bonus of a quaternary carbon site construction, posits a double bond primed for further manipulation. Rapid and general access to indoline building blocks as well pyrrolo[2,3-b]indole alkaloids and analogues appears to be feasible by this route (U. Anthoni, C. Christophersen, P. H. Nielsen In Alkaloids: Chemical and Biological Perspectives, Vol. 13; S. W. Pelletier, Ed.; Pergamon Press: New York, 1999, pp 163-236).