Julia olefination

What is Julia olefination?

The Julia olefination is a multistep process first reported by Julia in 1973. The reaction involves the addition of phenylsulfonyl carbanion to aldehydes or ketones, which forms β-hydroxysulfones. Subsequent esterification of the hydroxyl group and reductive elimination of β-sulfonyl esters with sodium amalgam produces trans-olefins.

Julia olefination - general reaction scheme
Julia olefination
  • R1, R2 = H, alkyl, aryl
  • R3 = alkyl, aryl
  • R4 = CH3CO; X = OCOCH3
  • or R4 = PhCO, CH3SO2; X = Cl (see list of acronyms)

Due to intrinsic weaknesses such as multiple steps, low tolerance for reducible functional groups, and the presence of mercury reagent, the original protocol has been extensively modified and extended by researchers such as Kocienski and Lythgoe, Julia, and Keck.

The applied heterocyclic sulfones include benzothiazol-2-yl sulfones (BT), 2-pyridinyl sulfones (Pyr),  1-phenyl-1H-tetrazol-5-yl sulfones (PT), and tert-butyl-1H-tetrazol-5-yl sulfones (TBT).

BT (heterocyclic sulfone) used in the modified Julia olefination
BT (heterocyclic sulfone) used in the modified Julia olefination
Pyr (heterocyclic sulfone) used in the modified Julia olefination
Pyr (heterocyclic sulfone) used in the modified Julia olefination
PT (heterocyclic sulfone) used in the modified Julia olefination
PT (heterocyclic sulfone) used in the modified Julia olefination
TBT (heterocyclic sulfone) used in the modified Julia olefination
TBT (heterocyclic sulfone) used in the modified Julia olefination

The application of heterocyclic sulfones in this olefination provides extra advantages, such as enabling more or less pronounced complexation between the heterocycle and metal cation to influence selectivity. Moreover, it undergoes nucleophilic substitution at the carbon attached to the sulfonyl group, which then becomes a leaving group. The electronic and steric nature of such sulfones does not affect the yield and selectivity of olefination. The stereoselectivity is controlled by the solvent used.

For example, more cis-olefins are formed in solvents such as toluene, methylene chloride, and diethyl ether, while more trans-olefins are produced in solvents such as DME and DMF (see list of acronyms).

The original Julia olefination protocol occurs via two mechanisms, depending heavily on the reducing agent. However, more recent experimental evidence prefers initial elimination of the ester to form vinyl sulfone, which would then undergo homolytic cleavage to give vinyl radical and finally transform into transolefin through vinyl anion.

The modified Julia olefination using heterocyclic sulfones proceeds via a different mechanism, involving the reversible addition of carbanion to carbonyl group.

References

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