Diastereoselective Ultrasonically Induced Zinc-copper Conjugate Addition to Chiral α,β-Unsaturated Carbonyl Systems in Aqueous Media

Abstract

The diastereoselective ultrasonically induced zinc-copper 1,4-addition of alkyl iodides to chiral α,β-unsaturated systems 1-3 in aqueous media is reported. The reaction of methylenedioxolanone 1 with a variety of alkyl iodides takes place in good yields and with high diastereomeric excess. The 1,4-addition to (Z)- and (E)-γ,δ-dioxolanyl-α,β-unsaturated esters 2 and 3 also proceeds with good yields: the Z-isomer 2 gives good diastereoselectivities while the reactions with the E-isomer 3 are non-stereoselective.

Key words

aqueous media - Michael additions - radical reactions - stereoselective synthesis - zinc-copper couple

References

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6

The use of deuterated solvents support this mechanism, see ref. 3c.

12

Representative Experimental Procedure: To a solution of the chiral Michael acceptor 1-3 (1 mmol) and alkyl iodide (4, 2 to 6 mmol) in aq EtOH (5 mL, 70%) was added CuI (2 mmol) and Zn (6 mmol). The resulting black mixture was sonicated (45-180 min) until complete consumption of α,β-unsaturated system was achieved (TLC test). The mixture was diluted with EtOAc (8 mL), sonicated during 10 min, and filtered through a short pad of Celite^®, washing the solids with EtOAc (3 × 25 mL). The organic phase was washed with brine (50 mL), dried, filtered, and concentrated in vacuo. The residue was purified by flash chromatography to afford, after concentration, the desired 1,4-addition product.

13

All new compounds gave satisfactory ¹H NMR, ¹³C NMR, HMRS or microanalytical data.

14

Epimerization of the conjugate addition products was not observed under the reaction conditions.

18

The stereochemistry of the major diastereomer was determined by conversion of the 1,4-addition products into the corresponding γ-butyrolactones and NOE experiments, see ref. 17c.

19

Yields and stereoselectivities are also similar, see ref.17c and ref. 17h.