No abstract

The 3,3-dimethylindoline-derived allenes 5 are conveniently prepared by organocuprate addition to 2-(phenylethynyl)-3,3-dimethyl-1-methylindolium triflate 4. Their thermal isomerization affords tetracyclic azepine derivatives 6. The semicyclic 2-amino 1,3-dienes 11, formed by spontaneous tautomerization of the corresponding aminoallenes, are transformed by thermal reaction into either tricyclic azepine derivatives 13 or benzothiophene-annelated azaheterocycles 14 and 15, depending on the ring size of the enamine moiety and the (hetero)aryl group at C-4 of the 2-dienamine.

Several nitrobenzyl-based photosensitive phosphoramide mustards were synthesized. The nitrobenzyl moiety was structurally varied to find the most promising prodrug candidates in respect to photorelease and activity of the alkylating species. The synthesis of these compounds proved to be applicable even in regard to compounds with additional functionalization. The target molecules 13a,b to 14 exhibited the expected red shift in their absorption spectra maximum compared to the parent nitrobenzyl moiety. As seen by UV and (31)P NMR spectroscopy, the phosphoramide mustard was quickly liberated upon irradiation with mercury arc lamps. Assaying the structurally different prodrugs on their alkylating activity showed that compounds 13b and 14, derived from secondary benzyl alcohols, are promising prodrug candidates. Their water solubility and the possibility of attaching macromolecules are encouraging vis-à-vis future investigations on their in vitro cytotoxicity.

Conjugate addition of organocuprates to the 2‐ethynyl‐substituted cyclic iminium triflates 3 generates aminoallenes which tautomerize immediately to semicyclic 2‐amino‐1,3‐dienes (6, 8) or exocyclic 1‐amino‐1,3‐dienes (9, 10) with the enamine function incorporated into or attached to a 5‐, 6‐, or 7‐membered ring. In those cases where tautomeric equilibria between the two aminodiene species are possible, the five‐membered ring exists virtually exclusively with an exocyclic enamine double bond, but the six‐membered ring prefers the exocyclic form. The seven‐membered ring can accomodate both forms quite well.