Ring-forming reactions, general

The intramolecular Heck reaction presented in Scheme 8 is also interesting and worthy of comment. Rawal s potentially general strategy for the stereocontrolled synthesis of the Strychnos alkaloids is predicated on the palladium-mediated intramolecular Heck reaction. In a concise synthesis of ( )-dehydrotubifoline [( )-40],22 Rawal et al. accomplished the conversion of compound 36 to the natural product under the conditions of Jeffery.23 In this ring-forming reaction, the a-alkenylpalladium(n) complex formed in the initial oxidative addition step engages the proximate cyclohexene double bond in a Heck cyclization, affording enamine 39 after syn /2-hydride elimination. The latter substance is a participant in a tautomeric equilibrium with imine ( )-40, which happens to be shifted substantially in favor of ( )-40. 

Generally speaking, the construction of a cyclic molecule composed of carbon atoms is nothing more than a particular case of carbon-carbon bond formation. Why is it necessary, then, to examine the ring-forming reactions in a special section The answer to this question becomes apparent if we consider briefly the specific features of the transformations that should occur in order to form a cyclic structure. 

Valuable preparative applications are rare and especially in ring-forming reactions other stereochemical factors such as ring strain and conformational effects will determine the stereochemistry. However the use of metal compounds to influence regio- and stereo-selectivity continues to excite interest. For C—C bond formation the coupling of allylic acetates with organocuprates offers broad synthetic potential as it generally seems to proceed with double bond shift. ... 

The synthesis of grandisol by Stork and Cohen illustrates the application of epoxynitrile cyclization, a facile general ring forming reaction developed at Columbia. ... 

Trialkylstannyl substitution has a similar effect on the chemical efficiencies of photocyclization reactions of phthalimido-linked polyethers and related maleimides. As seen by viewing the data compiled in Table 85.1, the yields for formation of the macrocycHc polyethers 32a-f are generally higher when the tin-substituted substrates 30a-f, rather than silicon-substituted substrates 31a-f, are irradiated. This is especially true in the case of the larger ring forming reactions. 

---