Stereochemical outcomes radical reactions

It could be shown that the stereochemical outcome of such radical polycycliza-tions is influenced by the nature of the substituents (H, Me, C02R). For instance, as in the example 3-225, the all-( )-methyl-substituted polyene 3-228 also gave the corresponding all-trans-anti polycycle 3-229 in the presence of Bu3SnH and AIBN. However, the ester-substituted polyene 3-230 led to the cis-anti-cis-anti-cis tetracycle 3-231 under similar reaction conditions (Scheme 3.60). A certain degree of preorganization of the precursor is assumed to be the reason for this result [97]. 

A few examples are chosen in order to illustrate the potentialities of this remarkable methodology. In Reaction (6.6) the sequence is initiated by the removal of the PhSe group and the formation of a carbamoyl radical. It is worth mentioning that the stereochemical outcome of these cascade reactions is controlled by the stereochemistry of the oxygen-bearing asymmetric carbon in 29. Indeed, Reactions (6.6) and (6.7) show clearly the stereochemical control. On the other hand, Reactions (6.7) and (6.8) illustrate the role of R which is carried as a terminal group in the acetylenic moiety. For R = Ph the last step is the hydrogen abstraction, whereas for R = SnBus, the last step is the ejection of BusSn radical (cf. Scheme 6.7). 

Scheme 6.2 represents Sj j l substitution that takes place when sodium thiophenolate attacks e,4-tert-butyl-c,2-methyl-fl,4-nitro-e,4-(4-nitrophenyl) cyclohexane. Light irradiation stimulates the reaction. It is carried out under nitrogen in HMPA. The ion-radical type of the process has been established by means of inhibitors. It was found that the stereochemical outcome of the reaction depends on the concentration of the PhSNa nucleophile. At a low concentration of PhSNa, the reaction leads to a mixture of phenylthiyl derivatives the content of a,SPh-substituted product is higher than that of c,SPh product by 20%. At a high concentration of PhSNa, the reaction produces practically a single stereoisomer bearing the a-PhS group. 

The phenylthionocarbonate procedure was also used for the cyclization of a 5-oxime-ether radical (Scheme 6) [17]. The stereochemical outcome of this reaction is almost identical with that observed for a closely related 6-methoxyhex-5-enyl radical cyclization [12,14]. A related glucosamine-derived radical cyclization has been employed for the synthesis of allosamizoline 13 [18]. Other examples in this area include the cyclization of... 

It is known that the geometries of the reactants play an important role in the regio-and stereochemical outcome of radical reactions since they are commonly involved in early transition states. Previous attempts to affect rotamer populations during the reaction included, among others, control of temperature and addition of a Lewis acid. It was recently reported75 that organotin halides, common byproducts of radical reactions, act... 

The material in Section 8.3 should be understood along with the already-discussed data in Chapters 1, 2, and 3. There are many examples in which the ion radical stage affects the stereochemical outcome of entire reactions. The stereochemistry of intermediary ion radicals obviously correlates with the steric characteristics of final products. Nevertheless, it... 

Radical carbonylation can also be conducted in a zinc-induced reduction system. A similar three-component transformation reaction to that illustrated in the second equation of Scheme 6.14 can be attained using zinc and protic solvents (Scheme 6.38) [59]. The observed stereochemical outcome is identical to that for the tin hydride-mediated reaction, providing a additional evidence for free-radical generation, radical carbonylation, and acyl radical cyclization taking place simultaneously, even in the zinc-induced system. In this system, however, the final step is reduction to form a carbanion and protonation. 

The observed 5-exo-trig cyclization in the above reaction is attributed to the formation of more stabilized malononitrile radical intermediate compared to the trialkyl-substituted radical. The stereochemical outcome of these transformations with regards to the malonodinitrile group is consistently P-sclcctivc this suggests least steric interactions between these substituents as compared to the alternative methyl-methyl interaction in the transition state. 

The reductive lithiation of substituted tetrahydropyrans such as 82 is stereoselective, producing principally the axial organolithium at -78 °C.81 Since reductive lithiation proceeds by fast reduction of a more slowly formed radical, the stereochemical outcome of the reaction... 

The P-addition of alkyl radicals to 4-methyl-2-(arylsulfinyl)-2-cyclopentenone 117 has been shown to occur in a completely stereocontrolled manner. Of a mixture of (4/ )- and (45)-117, only (4R)-117 reacts with t-Bu and i-Pr radicals to give the trans adducts 119a and 119b in 99% yield, while (45)-117 remained entirely unreacted. The stereochemical outcome of the reaction shows that the alkyl radical approaches from the side opposite to the aryl moiety in an antiperiplanar orientation to the carbonyl and sulfoxide bond. The 2,4,6-triisopropylphenyl group on sulfur plays a critical role, as it effectively shields the olefin face at the P-position by one of the isopropyl groups. This was confirmed by the 1 1 diastereomeric mixture obtained in the reaction of 4-methyl-2-(p-tolylsulfmyl)-2-cyclopentanone with the tert-butyl radical. 

The stereochemical outcome of the radical cyclisation step o is highly dependent on the use of a cyclic precursor (e.g. 7). When acyclic compound 12 was submitted to the same reaction conditions as in o, it cyclised to give 13. Give reasons for this finding. 

In their enantioselective total synthesis of (+)-triptocallol (3-79), a naturally occurring terpenoid, Yang and coworkers made use of a concise Mn(OAc)rmediated and chiral auxiliary-assisted oxidative free-radical cyclization [39]. Reaction of 3-77, bearing a (R)-pulegone-based chiral auxiliary, with Mn(OAc)3 and Yb(OTf)3 yielded tricyclic 3-78 in a twofold ring closure in 60% yield and a diastereomeric ratio of 9.2 1 (Scheme 3.20). A further two steps led to (-i-)-triptocallol (3-79). For the interpretation of the stereochemical outcome, the authors proposed the hypothetical transition state TS-3-80, in which chelation of the (3-keto ester moiety with Yb(OTf)3 locks the two carbonyl groups in a syn orientation. The attack of the Mn -oxidation-generated radical onto the proximate double bond is then restricted to the more accessible (si)-face, as the (re)-face is effectively shielded by the 8-naphthyl moiety. 

Jang et al. reported a highly diastereoselective tandem radical reaction to prepare -polysubstituted homoallylic alcohols (Scheme 64) [175]. This new process relies on the initial addition of benzoyl radicals onto an olefin. The intermediate radicals such as 201 underwent a stereoselective vinylation (two elementary steps) to form the desired Bz-protected homoallylic alcohols in good yields. The stereochemical outcome of the reaction is strongly dependent on polar factors such as solvent polarity of Lewis acid additives. More sophisticated domino processes including cyclizations can be devised, as is the case for the formation of 203. 

In the absence of Lewis acid the stereochemical outcome was controlled by the conformation of the starting radicals XIII (Sch. 11). Divalent Lewis acids such as MgBr2 or Mgl2 could alter the structure of the transition state XIV to the bidentate chelate, thus changing the diastereofacial selectivity of the addition reaction. 

Both intermolecular and intramolecular additions of carbon radicals to alkenes and alkynes continue to be a widely investigated method for carbon-carbon bond formation and has been the subject of a number of review articles. In particular, the inter- and intra-molecular additions of vinyl, heteroatomic and metal-centred radicals to alkynes have been reported and also the factors which influence the addition reactions of carbon radicals to unsaturated carbon-carbon bonds. The stereochemical outcome of such additions continues to attract interest. The generation and use of alkoxy radicals in both asymmetric cyclizations and skeletal rearrangements has been reviewed and the use of fi ee radical reactions in the stereoselective synthesis of a-amino acid derivatives has appeared in two reports." The stereochemical features and synthetic potential of the [1,2]-Wittig rearrangement has also been reviewed. In addition, a review of some recent applications of free radical chain reactions in organic and polymer synthesis has appeared. The effect of solvent upon the reactions of neutral fi ee radicals has also recently been reviewed. ... 

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