Microwave assisted [2+2+2] cyclotrimerizations

ORGN 130

Douglas D. Young, ddyoung@unity.ncsu.edu and Alexander Deiters, alex_deiters@ncsu.edu. Department of Chemistry, North Carolina State University, 2620 Yarbrough Drive, Box 8204, Raleigh, NC 27695
Five and six membered carbo- and heterocyclic ring systems represent privileged core structures in many biologically active compounds. Thus, a generally applicable means to generate these core structures will find broad application in the preparation of compound libraries for biological screens. The [2+2+2] cycloadditon reaction represents a practical route towards these core structures, but has been unexploited in combinatorial chemistry due to selectivity and reactivity issues associated with these reactions. Recently, we discovered that these issues can be resolved through the application of a solid-support in conjunction with the reactivity enhancing effects of microwave irradiation. This approach solves chemoselectivity issues and substantially improves problems associated with regioselectivity. Also, the utilization of microwave irradiation alleviates the requirements for long reaction times, the addition of additives, and the use of high catalyst loadings. These methodologies rapidly afford benzenes, pyridines, pyridones, imminopyridines, and other heterocyclic core structures in high yields and purities.