Regioselectivity control in the metal-catalyzed O-C functionalization of gamma-allenols, part 1: Experimental study.
We describe versatile regiocontrolled metal-catalyzed heterocyclization reactions of gamma-allenol derivatives leading to a variety of fused enantiopure tetrahydrofurans, dihydropyrans, and tetrahydrooxepines. Regioselectivity control in the O-C functionalization of gamma-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 gamma-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).
Alcaide
Benito
B
Departamento de Química Orgánica I, Facultad de Química, Universidad Complutense de Madrid, 28040 Madrid, Spain. alcaideb@quim.ucm.es
Almendros
Pedro
P
Martínez del Campo
Teresa
T
Soriano
Elena
E
Marco-Contelles
José L
JL
D000438:Alcohols / Q000138:chemical synthesis* / Q000737:chemistry*; D000466:Alkadienes / Q000138:chemical synthesis* / Q000737:chemistry; D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D003300:Copper / Q000737:chemistry*; D003500:Cyclization; D006046:Gold / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
D000438:Alcohols; D000466:Alkadienes; D000480:Alkynes; C025947:propadiene; D006046:Gold; D003300:Copper