Stereocontrolled Annulations of Indolo[2,3-a]quinolizidine-Derived Lactams with a Silylated Nazarov Reagent: Access to Allo and Epiallo Yohimbine-Type Derivatives.
The facial selectivity of double Michael addition reactions of the silylated Nazarov reagent 4 to unsaturated indolo[2,3-a]quinolizidine lactams 3 has been studied. Pentacyclic 3-H/15-H trans adducts 5 are generated from Nind -unsubstituted lactams, but the corresponding cis isomers 6 are formed when the indole nitrogen has a tert-butyloxycarbonyl (Boc) substituent. This reversal in the facial selectivity of the annulation has been rationalized by means of theoretical calculations, which indicate that the initial nucleophilic attack under stereoelectronic control is hampered by the presence of the bulky Boc group. The synthetic usefulness of the pentacyclic Nazarov-derived adducts is demonstrated by their conversion into allo and epiallo yohimbine-type targets.
Laboratory of Organic Chemistry, Faculty of Pharmacy and Institute of Biomedicine (IBUB), University of Barcelona, 08028 (Spain).
Federica
F
Arioli
Laboratory of Organic Chemistry, Faculty of Pharmacy and Institute of Biomedicine (IBUB), University of Barcelona, 08028 (Spain).
Maria
M
Pérez
Laboratory of Organic Chemistry, Faculty of Pharmacy and Institute of Biomedicine (IBUB), University of Barcelona, 08028 (Spain).
Celeste
C
Are
Department of Physical Chemistry, Faculty of Pharmacy and Institute of Biomedicine (IBUB), University of Barcelona, 08028 (Spain).
Carolina
C
Estarellas
Department of Physical Chemistry, Faculty of Pharmacy and Institute of Biomedicine (IBUB), University of Barcelona, 08028 (Spain).
F Javier
FJ
Luque
Laboratory of Organic Chemistry, Faculty of Pharmacy and Institute of Biomedicine (IBUB), University of Barcelona, 08028 (Spain).
Joan
J
Bosch
Laboratory of Organic Chemistry, Faculty of Pharmacy and Institute of Biomedicine (IBUB), University of Barcelona, 08028 (Spain). amat@ub.edu.
Mercedes
M
Amat
Michael addition; alkaloids; density functional calculations; stereoselectivity; synthesis design