Free radicals and Lewis acid. Chelation-controlled radical allylations of substituted α-halo- or α-phenylseleno-β-alkoxy esters. The endocyclic effect.

Abstract

The radical allylation of a series of α-halo or α-phenylseleno-β-alkoxy esters in the presence of MgBr2·OEt2 is reported and compared with analogous reactions under non-chelating conditions. The addition of MgBr2·OEt2 gives excellent selectivity favoring anti products; in some cases ratios >100:1 are obtained. Varying the substrate substituents reveals that these reactions are quite tolerant of alkyl functionalities at the β-position. Changes to the alkoxy function indicate that a chelate is involved in the reaction. The reactions are successful with secondary iodides, bromides, and phenylselenides, as well as tertiary iodides, which all give very high ratios under chelation control. Performing less well under the same conditions are substrates with a radical exocyclic to a tetrahydrofuran ring. EDTA titration is used to determine the amount of Mg2+ dissolved in the allylation reaction mixture, and 13C NMR is employed to better define the nature of the complex formed (chelate or monodentate) prior to the reaction. Competition experiments suggest that the chelate and monodentate pathways are in competition for the radical allylation with allyltributyltin.Key words: allylation, radicals, Lewis acid, stereoselectivity, 1,2-induction.

Thione Esters as Substrates for the Stereoselective Alkylation of Model Compounds of Nonactic Acids

“…The radical substitution reaction has been reported to yield preferentially the trans/syn and cis/syn diastereoisomers. [46,47] Assigning the relative configurations of the products obtained by the radical substitution process (Scheme 7) based on the literature report is compatible with the chemical correlation.…”

“…To achieve the radical substitution, we applied the excellent work of Guindon and co-workers (Scheme 7) [46,47] who described this reaction for a monosubstituted tetrahydrofuran. According to their report, the syn product is favoured in the absence of Lewis acids.…”

Phenylselenoethers as Precursors of Acyclic Free Radicals. Creating Tertiary and Quaternary Centers Using Free Radical-Based Intermediates

“…Since both faces of the radical could be attacked, this Importantly, carbon-carbon bond forming reactions were achieved with the same precursors. The addition of these electron poor radicals to electron rich double bonds, such as allyltributylstannane [24,25,26], led to the creation of stereogenic quaternary centers (Scheme 7) [14,27]. The transition states are similar and the sense of diastereoselectivity could be predicted by the rules described above.…”

Radical Reactions

“…11.5). Guindon and coworkers have obtained excellent diastereoselectivity for chelation-controlled allylation reactions of -halo--alkoxy esters using MgBr 2 ·OEt 2 as a Lewis acid and allyltrimethylsilane [30] or allylstannane [31] as the allylating agent. Interestingly, a reversal of selectivity was observed when no Lewis acid was used (entry 2).…”

“…However, less encouraging results were obtained when the radical was exocyclic to a tetrahydrofuran ring (Scheme 11.23, Tab. 11.6) [31]. The authors suggest that 299 the low selectivity in the reaction of 91a could involve a monodentate transition state 95.…”