Radical addition reactions stereochemistry

A sequence of reactions that was recently reported by Hanessian and Alpegiani nicely illustrates how the allylstannane method is useful for functionalization of complex, sensitive substrates and, more generally, how stereochemistry can be controlled in radical addition reactions (Scheme 40).138 Dibromo- 3-lac-tam (25) can be monoallylated with a slight excess of allyltributylstannane and then reduced with tributyltin hydride to provide 3-allylated (3-lactam (26) (the acid salt of which shows some activity as a 3-lactamase inhibitor). Stereochemistry is fixed in the reduction step hydrogen is delivered to the less-hindered face of the radical. Alternatively, monodebromination, followed by allylation, now delivers the allyl group from the less-hindered face to provide stereoisomer (27). Finally, allylation of (25) with excess allylstannane produces the diallylated product (not shown). 

There has been intense interest in the control of stereochemistry of free-radical addition reactions by use of chiral auxiliaries [6] and, even more recently, using enantioselec-tive catalysis [7-12]. As a result, the current understanding of stereochemical control has clearly progressed to the point where this obstacle can be overcome. There have also been reports of strategies that simplify telomer distribution in free-radical oligomeriza-... 

THE STEREOCHEMISTRY OF RADICAL SUBSTITUTION AND RADICAL ADDITION REACTIONS... 

If the radical addition reaction is performed in an intramolecular fashion, olefin activation with an electron-withdrawing group will not be a prerequisite for C-glycosylation, because the cyclization event competes well with hydrogen abstraction. In such examples, ring size and the stereochemistry of the ring substituents greatly influence the stereoselectivity and efficiency of the cyclization reaction. 

It was in 1994 that urea derivatives were employed as catalysts for the radical addition reactions, where addition of urea increased the reaction rate and also altered the stereochemistry in the allylation reaction of the sufinyl radical with... 

The Lead-Off Reaction Addition of HBr to Alkenes Students usually attach great-importance to a text s lead-off reaction because it is the first reaction they see and is discussed in such detail. 1 use the addition of HBr to an alkene as the lead-off to illustrate general principles of organic chemistry for several reasons the reaction is relatively straightforward it involves a common but important functional group no prior knowledge of stereochemistry or kinetics in needed to understand it and, most important, it is a polar reaction. As such, 1 believe that electrophilic addition reactions represent a much more useful and realistic introduction to functional-group chemistry than a lead-off such as radical alkane chlorination. 

From the point of view of both synthetic and mechanistic interest, much attention has been focused on the addition reaction between carbenes and alkenes to give cyclopropanes. Characterization of the reactivity of substituted carbenes in addition reactions has emphasized stereochemistry and selectivity. The reactivities of singlet and triplet states are expected to be different. The triplet state is a diradical, and would be expected to exhibit a selectivity similar to free radicals and other species with unpaired electrons. The singlet state, with its unfilled p orbital, should be electrophilic and exhibit reactivity patterns similar to other electrophiles. Moreover, a triplet addition... 

The absolute stereochemistry of the products formed from radical addition onto 2-propenyl sulfone and 1-phenylethenyl sulfone were found to be opposite. The reactions proceed through a five-membered transition state... 

The absolute stereochemistry for 150 (entries 2 and 3) was determined by hydrolysis and conversion to known compounds. Assuming a tetrahedral or cis octahedral geometry for the magnesium [110], the product stereochemistry is consistent with si face radical addition to an s-cis conformer of the substrate. This is the same sense of selectivity as that obtained with oxazo-lidinone crotonates or cinnamates suggesting that the rotamer geometry of the differentially substituted enoates is the same. The need for stoichiometric amount of the chiral Lewis acid to obtain high selectivity with 148 in contrast to successful catalytic reactions with crotonates is most likely a reflection of the additional donor atom present in the substrate. 

There are few addition reactions to a,/J-disubstituted enoyl systems 151 that proceed in good yield and are able to control the absolute and relative stereochemistry of both new stereocenters. This is a consequence of problematic A1,3 interactions in either rotamer when traditional templates such as oxazolidinone are used to relieve A1,3 strain the C - C bond of the enoyl group twists, breaking conjugation which results in diminished reactivity and selectivity [111-124], Sibi et al. recently demonstrated that intermolecular radical addition to a,/J-disubstituted substrates followed by hydrogen atom transfer proceeds with high diastereo- and enantioselectivity (151 -> 152 or 153, Scheme 40). 

Each of the syntheses of seychellene summarized in Scheme 20 illustrates one of the two important methods for generating vinyl radicals. In the more common method, the cyclization of vinyl bromide (34) provides tricycle (35).93 Because of the strength of sjp- bonds to carbon, the only generally useful precursors of vinyl radicals in this standard tin hydride approach are bromides and iodides. Most vinyl radicals invert rapidly, and therefore the stereochemistry of the radical precursor is not important. The second method, illustrated by the conversion of (36) to (37),94 generates vinyl radicals by the addition of the tin radical to an alkyne.95-98 The overall transformation is a hydrostannylation, but a radical cyclization occurs between the addition of the stannyl radical and the hydrogen transfer. Concentration may be important in these reactions because direct hydrostannylation of die alkyne can compete with cyclization. Stork has demonstrated that the reversibility of the stannyl radical addition step confers great power on this method.93 For example, in the conversion of (38) to (39), the stannyl radical probably adds reversibly to all of the multiple bond sites. However, the radicals that are produced by additions to the alkene, or to the internal carbon of the alkyne, have no favorable cyclization pathways. Thus, all the product (39) derives from addition to the terminal alkyne carbon. Even when cyclic products might be derived from addition to the alkene, followed by cyclization to the alkyne, they often are not found because 0-stannyl alkyl radicals revert to alkenes so rapidly that they do not close. 

---