Heteroatomic nucleophiles, Nicholas reaction

AppHcations of the treatment of a Co carbonyl-stabilized propargylic cation with nucleophiles to form a new C—C or carbon—heteroatom bond (Nicholas reaction) in the synthesis of natural products 12COC322. Approaches to dihydrooxazine ring systems and application in the synthesis of bioactive natural products 12KGS16. 

An underused property of cobalt-coordinated alkynes is the stabilization of propargyllic cations. The Nicholas reaction is a propargylic substitution reaction facilitated by the ability of the adjacent cobalt complex to stabilize the propargylic cation, 67 to 68. Both carbon and heteroatom nucleophiles have been used to effect this transformation. " This transformation has been been used as a strategy to introduce the alkene component for an intramolecular PKR. Shea has probed the use of an... 

Modifications to the standard Nicholas reaction generally fall into the following categories asymmetric reactions, use of heteroatom nucleophiles, use of metals other than cobalt, reactions of neutral electrophiles, reactions of carbocations not in the a-position, cycloadditions, and rearrangements. 

The use of heteroatom nucleophiles is a very popular variation of the Nicholas reaction. Alcohols and amines are most prevalent, while examples of azides, thiols,carboxylic acids, epoxides, hydrides, and fluorides are known. Isobe has made extensive use of alcohol nucleophiles in the preparation of various sized cyclic ethers. In studies directed toward the synthesis of ciguatoxin, Isobe converted alcohol 15 into eight-membered ring cyclic ether 16 using the Nicholas reaction. 

Kann recently investigated the intermolecular Nicholas reaction with substrates on the solid phase. In a detailed study with a variety of carbon and heteroatom nucleophiles, she demonstrated that the Nicholas reaction is a useful strategy for cleaving the substrate from the resin. Enyne 35 is available upon treatment of resin-bound cobalt-alkyne eomplex 34 with allyltrimethylsilane and boron trifluoride. Generation of the requisite carbocation results in eleavage from the polymer whieh is followed by a... 

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