Diastereoselective Multicomponent Cyclizations of Fischer Carbene Complexes, Lithium Enolates, and Allylmagnesium Bromide Leading to Highly Substituted Five- and Six-Membered Carbocycles

The one‐pot sequential reaction of a chromium alkoxycarbene complex, a ketone or ester lithium enolate, and allylmagnesium bromide enabled the selective synthesis of novel diastereomerically pure pentasubstituted cyclopentanols or tetrasubstituted 1,4‐cyclohexanediols, depending on the degree of substitution at the Cβ position of the enolate anion. A few exceptions have been encountered in which tetrasubstituted cyclopentanols or pentasubstituted 1,4‐cyclohexanediols were selectively formed. The use of 2‐iodoethoxycarbene complexes gave access to 1,2,4‐cyclohexanetriols. These multicomponent‐coupling reactions involved the formation of lithium alkylpentacarbonylchromates as key intermediates, which further evolved through intramolecular processes, such as insertion of an alkene, CO insertion or addition to a carbonyl group, and, moreover, could be trapped in intermolecular reactions with different electrophiles and styrene. The substitution pattern of the alkylchromate carbon chain has been proposed to control the nature of the annulation process. La reacción secuencial de un complejo alcoxicarbeno de cromo con un enolato de litio de cetona o de éster y bromuro de alilmagnesio generó, con total diastereoselectividad, nuevos ciclopentanoles pentasustituidos o 1,4‐ciclohexanodioles tetrasustituidos dependiendo del grado de sustitución del carbono en posición β del anión enolato. Algunas excepciones encontradas condujeron selectivamente a ciclopentanoles tetrasustituidos o 1,4‐ciclohexanodioles pentasustituidos a partir de enolatos de litio no sustituidos o monosustituidos en el carbono β, respectivamente. La utilización de complejos 2‐yodoetoxicarbeno permite obtener 1,2,4‐ciclohexanotrioles. En estas reacciones de acoplamiento multicomponente se forman intermedios de tipo alquilpentacarbonilcromato de litio que posteriormente evolucionan a través de procesos intramoleculares como inserción de un alqueno, inserción de un ligando carbonilo (CO) o adición a un grupo carbonilo y que, además, experimentan reacciones intermoleculares con diferentes electrófilos y estireno. Se propone que el patrón de sustitución de la cadena carbonada del alquilcromato controla la naturaleza del proceso de anulación. Organometallic cyclizations: A novel one‐pot synthetic sequence that transforms three/four simple starting materials into highly substituted and diastereomerically pure cyclopentanols or 1,4‐cyclohexanediols has been developed (see scheme). These multicomponent cycli