Reformatsky reaction

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Reformatsky reaction
Named after Sergey Reformatsky
Reaction type Coupling reaction
Identifiers
Organic Chemistry Portal reformatsky-reaction
RSC ontology ID RXNO:0000036

The Reformatsky reaction (sometimes spelled Reformatskii reaction) is an organic reaction which condenses aldehydes or ketones, with α-halo esters, using a metallic zinc to form β-hydroxy-esters:[1][2]

The Reformatsky reaction

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

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[5] and ethyl bromozincacetate[6] have been determined. Both form cyclic eight-membered dimers in the solid state, but differ in stereochemistry: the eight-membered ring in the ethyl derivative adopts a tub-shaped conformation and has cis bromo groups and cis THF ligands, whereas in the tert-butyl derivative, 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

Reaction Mechanism[edit]

Zinc metal is inserted into the carbon-halogen bond of the α-haloester by oxidative addition 1. This compound dimerizes and rearranges to form two zinc enolates 2. The oxygen on an aldehyde or ketone coordinates to the zinc to form the six-member chair like transition state 3. A rearrangement occurs in which zinc switches to the aldehyde or ketone oxygen and a carbon-carbon bond is formed 4. Acid workup 5,6 removes zinc to yield zinc(II) salts and a β-hydroxy-ester 7.[7]

RefRxn3.svg

Variations[edit]

In one variation of the Reformatsky reaction[8] an iodolactam is coupled with an aldehyde with triethylborane in toluene at -78 °C.

Reformatsky reaction Danishefsky variation[8]

See also[edit]

References[edit]

  1. ^ Reformatsky, S. (1887). "Neue Synthese zweiatomiger einbasischer Säuren aus den Ketonen". Berichte der Deutschen Chemischen Gesellschaft 20 (1): 1210–1211. doi:10.1002/cber.188702001268. 
  2. ^ Reformatsky, S. (1890). J. Russ. Phys. Chem. Soc 22: 44.  Missing or empty |title= (help)
  3. ^ Shriner, R. L. (1942). "The Reformatsky Reaction". Organic Reactions 1: 1–37. doi:10.1002/0471264180.or001.01. 
  4. ^ Rathke, M. W. (1975). "The Reformatsky Reaction". Organic Reactions 22: 423–460. doi:10.1002/0471264180.or022.04. 
  5. ^ Dekker, J.; Budzelaar, P. H. M.; Boersma, J.; van der Kerk, G. J. M.; Spek, A. J. (1984). "The Nature of the Reformatsky Reagent. Crystal Structure of (BrZnCH2COO-t-Bu · THF)2". Organometallics 9 (3): 1403–1407. doi:10.1021/om00087a015. 
  6. ^ Miki, S.; Nakamoto, K.; Kawakami, J.; Handa, S.; Nuwa, S. (2008). "The First Isolation of Crystalline Ethyl Bromozincacetate, Typical Reformatsky Reagent: Crystal Structure and Convenient Preparation". Synthesis 2008 (3): 409–412. doi:10.1055/s-2008-1032023. 
  7. ^ Kurti, L.; Czako, B. ‘‘Strategic Applications of Named Reactions in Organic Synthesis’’; Elsevier: Burlington, 2005.
  8. ^ a b Lambert, T. H.; Danishefsky, S. J. (2006). "Total Synthesis of UCS1025A". Journal of the American Chemical Society 128 (2): 426–427. doi:10.1021/ja0574567. 

See also[edit]