Gilman-Speeter reaction

What is Gilman-Speeter reaction?

In 1943, Gilman and Speeter first reported the Gilman-Speeter reaction, which involves the condensation of a Reformatsky reagent and an imine, to efficiently prepare 3-alkyl-substituted or unsubstituted β-lactams. This reaction is also known as the Gilman-Speeter condensation and is considered to include the extended reactions between lithium ester enolate or lithium thioester enolate and imine.

Gilman-Speeter reaction - general reaction scheme - Gilman-Speeter condensation
Gilman-Speeter reaction
  • R1 = Me, Et, i-Pr, Cy, t-Bu, etc.
  • R2i-Pr, Cy, t-Bu
  • R3 = alkyl, aryl
  • R4 = H, Me, aryl, etc. (see list acronyms)

Nonenolizable imines, such as N-aryl aldimines, are usually suitable for Gilman-Speeter reaction, and it offers easy access to starting materials and a simple preparation of 3-substituted or unsubstituted 2-azetidinones with direct control of stereoselectivities.

However, the yield of this reaction depends on the type and activation of zinc, and the stereochemistry of β-lactams is affected by the α-substituent of bromoacetates, the solvent, and the alkyl portion of the esters.

The use of ultrasound can enhance the reaction and increase the yields of β-lactams. Despite this, the Gilman-Speeter reaction has not been extensively studied due to its slow reaction rate and relatively low yields, which usually range from 20 to 50%.

References

The Reformatsky Reaction with Benzalaniline
Henry Gilman and Merrill Speeter
Journal of the American Chemical Society 1943 65 (11), 2255-2256
DOI: 10.1021/ja01251a503

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