Radical addition stereoselectivity

The stereoselectivity of the radical addition can be explained in terms of a bridged structure similar to that involved in discussion of ionic bromination of alkenes ... 

Similar stereoselectivities are achieved in the allylation of enantiomerically pure proline-derived a-oxoamides47. l-Bromo-3-methy]-2-butcne reacts with clean allylic inversion. Since pinacol-type coupling products are also produced under the reaction conditions, this was taken as evidence for a radical addition mechanism47. 

Free-radical addition of Se-phenyl areneselenosulfonates to acetylenes is also a facile process, occurring regiospecifically and stereoselectively to afford the E-isomer of a -(phenylseleno) vinyl sulfone (26) in high yield88. 

Stereospecificity of this reaction reaches 15 1 for telomer T3. Telomer T3 is a crystalline product, this allowed the authors to use X-ray diffraction analysis for studying stereochemistry. Stereoselectivity observed in the formation of T3 shows that both addition step and the step of halogen transfer to the growing radical proceed stereoselectively in this case. 

From a synthetic point of view, the regioselectivity and stereoselectivity of the cyclization are of paramount importance. As discussed in Section 11.2.3.3 of Part A, the order of preference for cyclization of alkyl radicals is 5-exo > 6-endo 6-exo > 7-endo S-endo > 1-exo because of stereoelectronic preferences. For relatively rigid cyclic structures, proximity and alignment factors determined by the specific geometry of the ring system are of major importance. Theoretical analysis of radical addition indicates that the major interaction of the attacking radical is with the alkene LUMO.321 The preferred direction of attack is not perpendicular to the it system, but rather at an angle of about 110°. 

In any consideration of stereoselectivity in radical addition to acylic substrates, interpretation of the results is complicated by the knowledge that alkenes may be converted, at least in part, into their geometrical isomerides by traces of bromine (or of HBr, i.e. by Br, cf. p. 315). This may, however, be minimised by working at low temperatures, and by using a high concentration of HBr. Thus addition of liquid HBr at -80° to cis 2-bromobut-2-ene (67) was found to proceed with high TRANS stereoselectivity, and to yield (68) almost exclusively ... 

The base-catalysed ring contraction of 1,3-dioxepanes offers an attractive route to 4-formyl tetrahydropyrans (Scheme 14) , whilst fused exo-cyclic dienes 27 result from the radical cyclisation of alkenyl iodides 26 (Scheme 15) <00OL2011>. Intramolecular radical addition to vinylogous sulfonates is highly stereoselective, leading to the ci s-2,6-disubstituted tetrahydropyran (Scheme 16) . 

Chiral l,3-dioxin-4-ones photochemically react intermolecular with (cyclic) ethers, acetals, and secondary alcohols to give the addition products in reasonable yields. The radical addition was completely stereoselective at C-6 of the heterocycle <1999EJO1057>. The exocyclic diastereoselectivity, where relevant, was about 2 1 (Equation 30). In analogy, an intramolecular cascade reaction of a 1,3-dioxin -one derived from menthone was used to get a terpenoid or a steroid framework in optically active form <1997JA1129, 1999JA4894>. 

In our group, we have explored the radical addition of alkyl radicals [97] and anomeric radicals [115] to sugar enones 134 having an exo double bond (see Schemes 46 and 47). Comparison of radical and anionic 1,4-addition, shown here, yields strictly equivalent stereoselectivities. The selectivity also depends on the nature of the entering radical, and reversal of stereoselectivity is observed on going from primary alkyl radicals to the larger t-butyl radical [for analogous observations see also Ref. 116]. 

Among the many variants that add two heteroatoms, those that add phenylsulfonyl groups are particularly useful because they proceed in high yield under mild conditions and provide functionality for subsequent synthetic transformations. The examples contained in Scheme 88 illustrate some recent applications.230-232 In contrast to most radical additions to alkynes, the additions of ArS X are often highly stereoselective. 

The addition of chloro azide CIN3 on the double bond of glycals proceeds by either an ionic or a radical mechanism depending on experimental conditions. Under UV irradiation, in solvents of low polarity and in the absence of oxygen, radical addition is predominantly regio- and stereoselective [51, 52]. The double bond reactivity is affected by the substituent at C-3 position and its inductive effect. Therefore, the presence of acetates lowers the reactivity, but azidosides are formed following Scheme 25. 

Enynes are also excellent substrates for tandem addition reactions. Pandey and co-workers have reported a photoinduced electron transfer (PET) promoted reaction of a selenium radical addition to an enyne [95T1483]. The high stereoselectivity observed in this cyclization is noteworthy. 

Highly diastereoselective alkyl radical addition to Oppolzer s camphorsultam derivative (33) of oxime provides enantiomerically pure a-alkyl-a-amino acid derivative (34) at — 78 °C by the same method as shown in eq. 10.16. Moreover, enantioselective tandem radical 1,2-difunctionalization of cinnamamide (35) can be carried out with high stereoselectivity, using the chelation manner of the cinnamamide and a chiral bisoxazoline ligand on Mgl2, as shown in eq. 10.17. 

Bertrand, S., Hoffmann, N., and Pete, J.-P. (2000) Highly efficient and stereoselective radical addition of tertiary amines to... 

Tandem radical addition/cydization reactions have been performed using unsaturated tertiary amines (Scheme 9.11) [14,15]. Radical attack is highly stereoselective anti with respect to the 5-alkoxy substituent of 2-(5f-J)-furanones, which act as the electron-deficient alkenes. However, the configuration of the a position of the nitrogen cannot be controlled. Likewise, tandem addition cyclization reactions occur with aromatic tertiary amines (Scheme 9.12) in this case, acetone (mild oxidant) must be added to prevent the partial reduction of the unsaturated ketone [14]. 

Radical Additions to Chiral Hydrazones Stereoselectivity and Functional Group Compatibility... 

Diastereoselectivity in radical additions to hydrazones 3 and 7 proved to be quite promising, with diastereomer ratios ranging from 93 7 to 99 1 (Table 3) [47]. In search of optimal stereocontrol, substituents on the oxazolidinone moiety were varied. Thus, isopropyl radical additions to several /V-acylhydrazones 3a-3e were compared for stereoselectivity (Scheme 3). High diastereoselectivities were observed in all adducts 13a-13e, although a rigorous measurement was not obtained on 13c. All of the auxiliaries impart stereocontrol suitable for practical synthetic application [48],... 

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