Olefin Asymmetric Organic Small Molecules Of Free Radicals Catalytic Cyclization Reaction Theory Research

The paper describes examples of net diastereotopic-group-selective radicalprocesses having the unusual feature that a single product is formed even though thekey reaction of the two diastereotopic radical precursors is nonselective. For example,reaction of (R)-N-(cyclohex-2-en-1-yl)-N-(2,6-diiodo-4-methylphenyl)acetamide withtributyltin hydride produces1-((4aR,9aR)-6-methyl-2,3,4,4a-tetrahydro-1H-carbazol-9(9aH)-yl)ethanone with high product selectivity and in high yield. Analysis of theDFT shows that nonselective abstraction of diastereotopic iodides by tin radicalsoccurs, leading to diastereomeric aryl radicals. These isomeric intermediates evolvevia two nonintersecting reaction pathways, cyclization and bimolecular trapping orvice versa, into the same final product.The paper describes the mechanism of a multi-pathways, one main productreaction in detail using DFT calculations. The calculation results suggest that there aresix possible pathways from reactants to products, and the free energy barriers of therate-determining steps of each pathway are almost equal. Different from usualreaction, the selectivity of this reaction is controlled by two competitive reactions, i.e.,cyclization and bimolecular trapping, instead of the rate-determining steps. In forks ofthe reaction pathways, cyclization reaction is more competitive than bimoleculartrapping reaction due to its low free energy barrier. Among the six pathways, ChannelC is the most dominant pathway and Channel A is the secondary one. In addition,which catalyst is effective in different steps is also investigated. From the results, itcan be concluded that tributyltin hydride as catalyst providing hydrogen atom is notalways suitable due to its large space distribution.Barriers to rotation of the N-alkenyl bond in a series of N-cycloalkenyl-N-benzylacetamide derivatives have been measured. Depending on substituents on theacetamide acyl group, the barriers range from9.7to14.2kcal/mol in experiment, andour computation is conformable. Polar solvents such as chloroform and methanolincrease the barrier to rotation compared to nonpolar solvents such as toluene. The relative order of the values of krotfor different acyl groups parallels their reported Esparamaters. For successful chirality transfer in5-endo trig radical cyclization, it isevident that rotations would need to be significantly slower than those reported here.Various N-(hex-5-enyl)-2-iodoalkanamides undergo efficient and regioselective9-endo iodine-atomtransfer radical cyclization reactions at room temperature. Thecyclized products were readily converted to the corresponding azonan-2-ones byreduction with Bu3SnH or to hexahydroindolizin-3(5H)-ones by treatment withaqueous Na2CO3in a one-pot, two-stage manner.