Chemical Sciences: A Manual for CSIR-UGC National Eligibility Test for Lectureship and JRF/Named Reactions/Reformatsky Reaction

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The Reformatsky reaction (sometimes spelled Reformatskii reaction) is an organic reaction which condenses aldehydes (or ketones), 1, with α-halo esters, 2, using a metallic zinc catalyst to form β-hydroxy-esters, 3.[1][2] It was discovered by Sergey Nikolaevich Reformatsky.

The Reformatskii reaction

The organozinc reagent, also called a 'Reformatskii enolate', is prepared by treating an alpha-halo ester with zinc dust. Reformatskii enolates are less reactive than lithium enolates or Grignard reagents and hence nucleophilic addition to the ester group does not occur.

Some reviews have been published.[3][4]

Structure of the reagent[edit]

The crystal structures of the THF complexes of the Reformatsky reagents tert-butyl bromozincacetate[1] and ethyl bromozincacetate[2] have been determined. Both form cyclic eight-membered dimers in the solid state, but differ in stereochemistry: the eight-membered ring in the ethyl derviative adopts a tub-shaped conformation and has cis bromo groups and cis THF ligands, whereas in the tert-butyl derviative, the ring is in a chair form and the bromo groups and THF ligands are trans.

Ethyl-bromozincacetate-from-xtal-3D-sticks-C.png
Ethyl-bromozincacetate-THF-dimer-from-xtal-2D-skeletal-D.png
Tert-butyl-bromozincacetate-from-xtal-3D-sticks-C.png
Tert-butyl-bromozincacetate-THF-dimer-from-xtal-2D-skeletal-D.png
ethyl bromozincacetate dimer
tert-butyl bromozincacetate dimer

Variations[edit]

In one variation of the Reformatsky reaction[5] an iodolactone is coupled with an aldehyde with triethylborane in toluene at -78°C.

Reformatsky reaction Danishefsky variation ref. Lambert 2006

References[edit]

  1. J. Dekker, P. H. M. Budzelaar, J. Boersma, G. J. M. Van der Kerk, A. J. Spek (1984). "The nature of the Reformatsky reagent. Crystal structure of (BrZnCH2COO-t-Bu.THF)2". Organometallics 9 (3): 1403–1407. doi:10.1021/om00087a015. 
  2. S. Miki, K. Nakamoto, J. Kawakami, S. Handa, S. Nuwa (2008). "The First Isolation of Crystalline Ethyl Bromozincacetate, Typical Reformatsky Reagent: Crystal Structure and Convenient Preparation". Synthesis 2008: 409–412. doi:10.1055/s-2008-1032023. 

Bibliography[edit]

  1. ^ Reformatskii, S., Neue Synthese zweiatomiger einbasischer Säuren aus den Ketonen, Ber. 1887, 20, 1210. doi:10.1002/cber.188702001268
  2. ^ Reformatskii, S. J. Russ. Phys. Chem. Soc. 1890, 22, 44.
  3. ^ Shriner, R. L. Org. React. 1942, 1, 1. (Review)
  4. ^ Rathke, M. W. Org. React. 1975, 22, 423. (Review)
  5. ^ Total Synthesis of UCS1025A Tristan H. Lambert and Samuel J. Danishefsky J. Am. Chem. Soc. 2006, 128(2), 426 - 427. (Communication) doi:10.1021/ja0574567 Abstract