Addition-fragmentation expansion

An alternate radical-induced addition-fragmentation sequence relies on the 1,4-elimination of a leaving group to drive the reaction. In this sequence, because the fragmentation is accompanied by the expulsion of a tiibutylstannyl radical, the requirement for the initial tributyltin hydride is only catalytic (Scheme 79). The stereospecificity of the reaction course has been rationalize in terms of a conformational preference for the elimination step, as depicted in Scheme 79 where the rran.r-substituted cyclohexanone forms only one double bond geometry in the product. As shown in equations (40) and (41), the ci.r-substituted cyclohexanones undergo the four- and three-carbon expansions stereospecifically to give the (Z)-alkenes. 

More recently, a radical-mediated variation of this addition-fragmentation has been explored. The reaction, summarized in Scheme 77 for a one-carbon expansion, involves the generation of a radical at the terminus of a chain by homolytic cleavage of a carbon-heteroatom bond. Addition of the radical to the carbonyl produces a bicyclic intermediate, which on cleavage of the alternate bond regenerates the ketone carbonyl group with formation of a new radical. The sequence is terminated by the reduction of the radical with the tributyltin hydride reagent. The near neutral conditions of the reaction avoid the reclo-... 

The selection of the thirty procedures clearly reflects the current interest of synthetic organic chemistry. Thus seven of them illustrate uses of T1(I), T1 (III), Cu(I), and Li(I), and three examples elaborate on the process now termed phase-transfer catalysis. In addition, newly developed methods involving fragmentation, sulfide contraction, and synthetically useful free radical cyclization arc covered in five procedures. Inclusion of preparations and uses of five theoretically interesting compounds demonstrates the rapid expansion of this particular area in recent years and will render these compounds more readily and consistently available. 

The key cyclization in Step B-2 was followed by a sequence of steps that effected a ring expansion via a carbene addition and cyclopropyl halide solvolysis. The products of Steps E and F are interesting in that the tricyclic structures are largely converted to tetracyclic derivatives by intramolecular aldol reactions. The extraneous bond was broken in Step G. First a diol was formed by NaBH4 reduction and this was converted via the lithium alkoxide to a monomesylate. The resulting (3-hydroxy mesylate is capable of a concerted fragmentation, which occurred on treatment with potassium f-butoxide. 

Since mechanistic information for cluster expansions is scarce it cannot be excluded that all such reactions described so far proceed via the addition of coordinatively unsaturated mononuclear complex fragments, even though they can be formulated differently. It is likely that most uncontrolled reactions changing the cluster nuclearity do proceed this way. However, there are a small number of simple cluster expansions which can be understood best by assuming intermediate fragments. This was already taken into account in the previous paragraph. It holds for the following reactions between clusters and simple complexes which do not bear an obvious center of reactivity. 

Pattenden and Schulz have reported that treatment of the acetylene derivative 43 with (TMS)3SiH leads, in one pot, to the bicyclic compound 44 in 70% yield (equation 71)". The proposed mechanism involves (TMS)3Si radical addition to the triple bond to form a vinyl radical followed by a remarkable cascade of radical cyclization-fragmentation-transannulation-ring expansion and termination via ejection of the (TMS Si radical to afford the bicyclic product. 

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