A Convenient Synthesis of (E)-α,β-Unsaturated Esters with Total Stereoselectivity Promoted by Catalytic Samarium Diiodide

Abstract

Synthesis of (E)-α,β-unsaturated esters in high yields and with total stereoselectivity is achieved from α-halo-β-hydroxy esters promoted by catalytic amounts of SmI₂. The starting compounds were easily prepared from α-halo esters and aldehydes as a mixture of stereoisomers. A mechanism is proposed to explain this samarium(II)-promoted catalytic β-elimination reaction.

α,β-unsaturated esters - catalytic reactions - eliminations - samarium

References and Notes

For reviews concerning the synthetic applications of SmI₂, see:

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7

To see a review about β-elimination reactions promoted by SmI₂, see ref. 1j.

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15

General Procedure for the Synthesis of Aliphatic ( E )-α,β-Unsaturated Esters 4a-c: A solution of the requisite α-halo-β-hydroxy ester 3a-c (0.2 mmol) in THF (2.5 mL) was added dropwise at r.t. and vigorous stirring to a mixture of SmI₂ (0.1 M in THF, 0.8 mL) and activated magnesium (1.2 mmol) with TMSCl (1.2 mmol) in THF (2.5 mL). After stirring at the same temperature for 18 h, the excess of SmI₂ was removed by bubbling a stream of air through the solution. An aqueous solution of 0.1 N HCl (10 mL) was then added and the aqueous phase was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were dried over anhyd Na₂SO₄, filtered and concentrated in vacuo. Flash column chromatography on silica gel (hexane-EtOAc, 5:1) provided pure compounds 4a-c.

16 Kunishima M. Nakata D. Sakuma T. Kono K. Sato S. Tani S. Chem. Pharm. Bull.  2001,  49:  97 

17

General Procedure for the Synthesis of Aromatic ( E )-α,β-Unsaturated Esters 4d-i: A solution of the requisite α-halo-β-hydroxy ester 3d-i (0.2 mmol) in THF (2.5 mL) was added dropwise at r.t. and vigorous stirring to a mixture of SmI₂ (0.1 M in THF, 0.8 mL) and activated magnesium (1.2 mmol) with iodine and zinc dichloride (1.2 mmol) in THF (2.5 mL). After stirring at the same temperature for 18 h, the excess of SmI₂ was removed by bubbling a stream of air through the solution. An aqueous solution of 0.1 N HCl (10 mL) was then added. The aqueous phase was filtered through a pad of celite^® and extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layers were dried over anhyd Na₂SO₄, filtered and concentrated in vacuo. Flash column chromatography on silica gel (hexane-EtOAc, 5:1) provided pure compounds 4d-i.

18 Wittig reactions carried out with enolizable carbonyl compounds can generate alkenes in very low yield: Maryanoff BE. Reitz AB. Chem. Rev.  1989,  89:  863 

19 Spectroscopic data of compound 4a has been described in: Concellón JM. Pérez-Andrés J. Rodríguez-Solla H. Angew. Chem. Int. Ed.  2000,  39:  2773 

Spectroscopic data of compounds 4b-g and 4i have been described in the following references:

20a

For compounds 4b, 4c and 4f see, ref. 19.

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20e For compound 4i, see: Dolby LJ. Riddle GN. J. Org. Chem.  1967,  32:  3481 

Other six-membered ring transition state models have been proposed to explain the selectivity in other reactions of SmI₂:

21a Molander GA. Etter JB. Zinke PW. J. Am. Chem. Soc.  1987,  109:  453 

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21e

See also refs 1j and 8-13.

22

This model assumes that the transformation of diastereoisomeric mixture of 3 leads only to the stereoisomer of appropriate conformation for coordination of the samarium(III) center by the hydroxy group.