The First Sequential Reaction Promoted by Manganese: Complete Stereoselective Synthesis of (E)-alpha,beta-Unsaturated Esters from 2,2-Dichloroesters

Link: JOC ASAP

José M. Concellón,* Humberto Rodríguez-Solla, Pamela Díaz, and Ricardo Llavona

Departamento de Química Orgnica e Inorgnica, Facultad de Química, Universidad de Oviedo, Julin Clavería 8, 33071 Oviedo, Spain

Mn has increasingly received much interest as a reagent/catalyst in organic transformation with its reactivity profile similar to SmI2 and CrCl2 but much less toxic and less expensive. In this current paper, activated Mn (Mn*) was used in refluxing THF to effect the following transformation with high stereoselectivity giving products in high yields.

Importantly, the Mn* system was able to transform inexpensive dichloroacetate ester derivatives in the presence of aldehydes to give both di- and trisubstituted alpha,beta-unsaturated esters in refluxing THF. The system also worked with dibromoacetate ester derivatives at rt. However, the dibromoacetate ester derivatives are generally more expensive than the dicholo-counterparts. Enolizable aldehydes could be used to effectively form the desired ester product without problem. However, when ketone was used in place of aldehyde, mixture of unidentifiable products was formed.

For the transformation below, activated Mn* was prepared by treatment of mixture of MnCl2 (13 mmol) and LiCl (26 mmol) with a slurry of lithium powder (26 mmol) at rt.

In comparative studies, some of these transformations to disubstituted products were compared with results using SmI2 and CrCl2 and Mn* was found to be superior in most cases as shown in Table 1.

To show versatility of this reaction, trisubstituted products could also be made. And these results are summarized in Table 2.

All products, both di- and trisubstituted enoates, were formed stereoselectively to yield only E-enoates. All of these transformations were believed to be a sequential processes starting from aldol reaction, followed by beta-elimination, all in one step. Selectivity of the reaction was believed to stem from TS-I where bulky R1 was placed in the pseudo-equatorial position. This is also illustrated in Fisher projection of TS-II. Scheme 2 demonstrates the proposed mechanism and transition states.