Abstract
Guiding cyclization: The 5‐exo‐trig cyclization pathway of γ‐allenols can be completely reversed either by changing the metal (Pd instead of Au) or by using a methoxymethyl protecting group, with 7‐endo‐trig alkoxycyclization then dominating instead (see scheme). In addition, the regioselectivity of the La‐catalyzed cycloetherification can be modulated (5‐exo versus 6‐endo versus 7‐endo) simply through subtle variation in the functionalization of the allene component.magnified image
We describe versatile regiocontrolled metal‐catalyzed heterocyclization reactions of γ‐allenol derivatives leading to a variety of fused enantiopure tetrahydrofurans, dihydropyrans, and tetrahydrooxepines. Regioselectivity control in the OC functionalization of γ‐allenols can be achieved through the choice of catalyst: use of AuCl~3~ exclusively affords tetrahydrofurans, use of La[N(SiMe~3~)~2~]~3~ usually favors the formation of dihydropyrans, whereas use of PdCl~2~ solely gives tetrahydrooxepines. In addition, it has been observed that for the Au‐catalyzed cycloisomerization, the presence of a methoxymethyl protecting group not only masks a hydroxy functionality, but also exerts directing effects as a controlling unit in a regioselectivity reversal (7‐endo versus 5‐exo cyclization). In addition, the regioselectivity of the La‐catalyzed cycloetherification can be tuned (5‐exo versus 7‐endo) simply through a subtle variation in the substitution pattern of the allene component (Ph versus Me). Thus, for the first time the regiocontrolled heterocyclization of γ‐allenol derivatives is both catalyst‐ and substrate‐directable. These metal‐catalyzed heterocyclization reactions have been developed experimentally (Part 1, this paper), and their mechanisms have additionally been investigated by a theoretical study (Part 2, accompanying paper).