Radical prochiral

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 addition of (TMS)3SiH to prochiral diethyl methyl fumarate (5) gave both diastereoisomers with preferential formation of the threo isomer (Reaction 5.7) [25]. This suggests that the intermediate adduct 6 adopts a preferred conformation due to the allylic strain effect, in which the silyl moiety shields one face of the prochiral radical center, favouring hydrogen transfer to the opposite face, and therefore the threo product is predominantly formed. 

The mode of asymmetric induction can be rationalized from the mechanism of the photopinacolization in the presence of aliphatic amines. The electron transfer from the amine to the excited triplet ketone furnishes charge transfer complex 5, from which a radical pair is formed by protoirtransfer. The weakly coordinated chiral amine seems to favor the dimerization of radical 6 from the si face leading to the (/ , ft)-enantiomer 3. The much lower selectivities observed with methanol as the cosolvent (3% ee at 27°C) indicate dipolar or hydrogen bonding interactions between the chiral diamine and the prochiral radical (Scheme 4). 

In simplified Scheme 13.6, both prochiral radical pairs are combined implicitly into one, so that Pi = ki/(ki + k + k ), P i = kJ ki + k + kk). Thus, kiKQ.Qlko regardless of the -aIkane or temperature among those investigated. Relating the two schemes,/Tq is approximately/ esc + 2b + /24B, and/tj equals 3 multiplied by the fraction of prochiral-(R) radical pairs that become prochiral-(5) radical pairs. Since S is essentially constant as well, viscosity- or temperature-induced changes of ki and the sum or the dominant term of (/ esc + 2b + 4b) must be proportional. 

The major cause of difficulty in achieving stereoselectivity in free radical reactions lies within the nature of the prochiral carbon-centred radical. Experimental evidence suggests that prochiral radicals are almost planar and essentially sp2 hybridised, with the unpaired electron occupying an unhybridised p-orbital located perpendicular to the plane of substitution (Figure 7.1).30... 

In general, diastereoselective reactions are those in which the radical undergoes a selective reaction with a prochiral radical trap. Control of stereoselective outcome in these reactions to be achieved through ... 

Figure 7.1 A prochiral radical being attacked from above or below during a stereoselective radical transformation.

The conformation should be such that the different substituents on the controlling stereocentre differentiate between the diastereofaces of the reacting prochiral radical. 

Facial selectivity induced by a stereogenic carbon atom in a-position to the radical center has been probed with acyclic and cyclic radicals [103], In the first cases, 2-substituted malonates 65-68 served as precursors for the prochiral radicals these were coupled in moderate yields with coradicals formed from acetic acid and the acids 34 and 35 (Eq. 9). 

A prochiral radical intermediate is generated from a-methoxymethyl-a-iododihy-drocoumarin (la) which is coordinated via the carbonyl oxygen to the chiral Lewis acid/ligand combination of MgL and 2. Enantiomeric excesses of up to 62% and yields of 88% have been obtained in this enantioselective reduction using tributyltin... 

Stereoselective Trapping of Prochiral Radicals with Chiral Nitroxides... 

Prochiral carbon radicals have enantiotopic faces reaction with chiral nitroxides can result in two possible diastereomeric products (Scheme 9). Our laboratory has been investigating the ability of chiral nitroxides to differentiate between the two enantiotopic faces of a transient prochiral carbon radical. In many of the examples, the prochiral radical is generated by the lead dioxide oxidation of a secondary benzylic hydrazine. Early work utilized a camphor-derived nitroxide 27, which was coupled to a secondary benzylic prochiral carbon radical with low but reproducible stereoselectivity (Scheme 10) [26]. The stereoselectivity jumped dramatically upon moving to a conformationally rigid nitroxide in the form of the steroid doxyl radical... 

Scheme 9. Reaction of a chiral nitroxide with the enantiotopic faces of a prochiral radical...

Also, it was demonstrated that acyclic radicals can react with high stereoselectivity [45]. In order for the reactions to be stereoselective, the radicals have to adopt preferred conformations where the two faces of the prochiral radical centers are shielded to different extents by the stereogenic centers. Giese and coworkers [49] demonstrated with the help of Electron Spin Resonance studies that ester-substituted radicals with stereogenic centers in (3-positions adopt preferred conformations that minimize allylic strain [49] (shown below). In these conformations, large (L) and medium sized substituents (M) shield the two faces. The attacks come preferentially from the less shielded sides of the radicals. Stereoselectivity, because of A-strain conformation, is not limited to ester-substituted radicals [50]. The strains and steric control in reactions of radicals with alkenes can be illustrated as follows [50] ... 

Secondly, radical polymerization of monomers possessing a chiral auxiliary can also afford highly isotactic rich polymer. In such monomer systems, tacticity is not determined by relative 1,3-interactions between the stereo-genic center of the penultimate unit and the prochiral radical center. Instead, the (enantiomerically pure) chiral auxiliary imposes a preference for the formation of either (R) or (S) absolute stereogenic centers at the prochiral... 

LA-mediated diastereocontrol in radical transformations involving chiral oxazolidinone substrates originates from the formation of a rigid 6-membered chelate complex. In the absence of LA, the oxazolidinone substrate radical (or alkenes) can adopt two conformations, in which the two carbonyl groups are either syn- or antiperiplanar (Figure 9). In the synper-iplanar conformation, the substituent of the oxazolidinone is in close proximity to the a-prochiral radical and shields the bottom face from allylation. However, in the antiperiplanar conformation, the R substituent is... 

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