Radical inverse

Rychnovsky et al. considered the formation of achiral conformers from chiral molecules and trapping the prochiral radical with a hydrogen atom donor based on memory of chirality (Scheme 12) [41], The photo-decarboxylation of optically active tetrahydropyran 40 leads to an intermediate 43, which now does not contain a stereocenter. If the intermediate 43 can be trapped by some hydrogen atom source before ring inversion takes place, then an optically active product 41 will be formed. This is an example of conformational memory effect in a radical reaction. It was reported that the radical inversion barrier is low (< 0.5 kcal/mol) while the energy for chair flip 43 44 is higher (5 to... 

The photochemical reduction of Barton ester 40 is depicted in Scheme 12. A series of hydrogen atom donors were screened. A stoichiometric amount of benzenethiol at - 78 °C provided the product in 86% ee (entry 3). This implies that, in the presence of an efficient hydrogen atom donor, radical trapping is competitive with the ring/radical inversion, generating an enantiomeri-... 

Several years ago in Chicago, we were engaged in developing a solution to the well-known )8-mannoside problem [19] involving the inversion of the much more readily accessible a-mannosides by a sequence of hydrogen atom abstraction, radical inversion, and diastereoselective quenching (Scheme 5) [20,21],... 

Sanxing Sun, a new student, sought to prepare more of the a-disaccharide (17) and subsequently to improve the radical inversion process. He repeated Brunckova s preparation with the minor, hut fortuitous, difference that the sulfoxide was activated with triflic anhydride before addition of the acceptor alcohol. To our amazement, an excellent yield was obtained of an anomeric mixture favoring the j8-maimoside by a factor of roughly 10 (Scheme 7) [26,27]. 

Crich has also taken advantage of the driving force for anomeric radical inversion in the formation of -mannopyranosides [15, 16]. In this case, an intramolecular... 

Crich has reported another example of anomeric radical inversion which involves a Barton reductive decarboxylation [17] of mannoulosonic acid glycosides to generate )5-mannopyranosides (Scheme 9) [16]. Photolysis of the intermediate O-acyl thiohydroxamate in the presence of r-BuSH cleanly affords the requisite jS-anomer. 

Using a related anomeric radical inversion concept, Curran has synthesized P-mannopyranosides from their corresponding a-epimers via an intramolecular 1,6-... 

Scheme 9. Barton decarboxylation/radical inversion in the synthesis of ) -mannosides...

Scheme 10. Anomeric radical inversion via radical translocation...

In general, free radicals are rapidly equilibrating intermediates, which makes stereoselective radical reactions extremely challenging. In ring systems that have little or no conformational bias, reactive radical intermediates can racemize either by a conformational interconversion (i.e., ring flip) or by a simple radical inversion. For simple 2-tetrahydropyranyl radicals, the barrier to radical inversion has been estimated to be <1 kcal/mol, while the barrier to ring inversion is 10 kcal/mol. Therefore, if conformational interconversion is slow relative to reaction of the radical intermediate, then non-equilibrium radical reactions are possible. Recently it has been shown that reduction of 2-tetrahydropyranyl radicals can be competitive with conformational interconversions, which allows for a new strategy for the control of stereochemistry in radical reactions [28]. 

The inversion of the cyclohexyl radical can occur by a conformational process. This is expected to have a higher barrier than the radical inversion, since it involves bond rotations very similar to the ring inversion in cyclohexane. An of 5.6kcal/mol has been measured for the cyclohexyl radical. " A measurement of the rate of inversion of a tetrahydropyranyl radical k = 5.7 x 10 at 22°C) has been reported. ... 

It can be concluded from these data that radical inversion is also fast in cyclic systems. 

FIGURE 54.28 Suggested mechanisms of RAFT interfacial inverse miniemulsion polymerization and free-radical inverse miniemulsion polymerization with NIPAM as the monomer as illustrated in Part (a) and (b), respectively. (Reprinted with permission from Macromolecules, 43(1), Lu, F.J., Luo, Y.W., Li, B.G., Zhao, Q., and Schork, F.J., Synthesis of thermo-sensitive nanocapsules via inverse miniemulsion polymerization using a PEO-RAFT agent, 568. Copyright 2010 American Chemical Society.)... 

Qi, G. Eleazer, B. Jones, C.W. Schork, F.J. Mechanistic aspects of sterically stabilized controlled radical inverse miniemulsion polymerization. Macromolecules 2009, 42 (12), 3906-3916. 

CFj-CFBr-CHPh CHj yields the same cis-trans mixture of l,l,2-trifluoro-3-phenylcyclobutanes, indicating that if the a-fluorocyclobutyl radical is non-planar its rate of inversion is faster than that of the a-fluorocyclopropyl radical energy barriers for radical inversions, calculated using the CNDO/2 approximation, can be correlated with this and other observations on radical inversions (see the Table). 

Fig. 2 TEM images of the latex obtained after (a) RAET interfacial inverse miniemulsion polymerization of NIP AM and (b) free radical inverse miniemulsion polymerization of NIP AM. Reproduced from [44] with permission from the American Chemical Society...

---