Nature Chemical Biology introduces the stitch of cyclohexanes with six contiguous stereocenters in a tandem [2+2+2] cycloaddition reaction accomplished by the Lanzhou Institute of Chemical Physics of the Chinese Academy of Sciences (LICP) in its article entitled Domino reactions: Chiral cycloaddition (Nature Chemical Biology, 2012, 8, 3, 223) published on February 15.
The article reports the first copper-catalyzed highly diastereo- and enantioselective asymmetric tandem reaction for the construction of highly functionalized cyclohexane arboxylates with six stereogenic centers developed by the research group headed by Prof. HUANG Hanmin of the State Key Laboratory for Oxo Synthesis and Selective Oxidation of the LICP (Angew. Chem. Int. Ed.2012, 51, 1248 –1251). The article describes that “Domino reactions offer facile access to complex molecular architectures, often with exquisite stereochemical control. Shi et al. provide an elegant example of this approach in a new [2+2+2] cycloaddition reaction combining Michael and Henry reactions to access a cyclohexane product with stereochemically defined substituents at each ring carbon.”
Contiguous multiple stereocenters are a highly desirable structural motif found in natural and synthetic bioactive compounds. Although a method for generating chiral compounds with eight contiguous stereocenters has been reported previously, two steps were needed to perform it. Two other groups have reported cyclohexanes with six contiguous stereocenters, but either as a by-product or in low yield and without providing the absolute structures of the compounds.
Just like the article says, “The reaction proceeds at room temperature and gram scale using only 0.1 mol% catalyst, and so it should provide straightforward entry into a variety of complex synthetic routes.”
The work has also been reported by SYNFROM as“Synstories”.