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 transliterated as Reformatskii reaction) is an organic reaction which condenses aldehydes or ketones with α-halo esters using metallic zinc to form β-hydroxy-esters:[1][2]

The Reformatsky reaction
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]

In addition

nitrones.[8] Moreover,[5] metals other than zinc have also been used, including magnesium,[9] iron,[10] cobalt,[11] nickel,[12] germanium,[13] cadmium,[14] indium,[15][16] barium,[17] and cerium.[18] Additionally,[5] metal salts are also applicable in place of metals, notably samarium(II) iodide,[19][20] chromium(II) chloride,[21] titanium(II) chloride,[22] cerium(III) halides such as cerium(III) iodide,[23] and titanocene(III) chloride.[24]

Structure of the reagent

The crystal structures of the THF complexes of the Reformatsky reagents tert-butyl bromozincacetate[25] and ethyl bromozincacetate[26] 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. Note that, in contrast to lithium and boron enolates, which have the metal(loid)s exclusively bond to oxygen, the zinc enolate moiety in the Reformatsky reagents have zinc atoms that are simultaneously O- and C-bound and can therefore be described as "organometallic".



ethyl bromozincacetate dimer tert-butyl bromozincacetate dimer

Reaction mechanism

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.[5]

Variations

In one variation of the Reformatsky reaction[27] an iodolactam is coupled with an aldehyde with triethylborane in toluene at -78 °C.

Reformatsky reaction Danishefsky variation[27]
Reformatsky reaction Danishefsky variation[27]

See also

References

  1. doi:10.1002/cber.188702001268
    .
  2. ^ Reformatsky, S. (1890). "Action of zinc and ethyl chloroacetate on ketones and aldehydes". J. Russ. Phys. Chem. Soc. 22: 44.
  3. ISBN 9780471264187
    .
  4. ISBN 0471264180
    .
  5. ^ a b c d Kurti, L.; Czako, B. Strategic Applications of Named Reactions in Organic Synthesis; Elsevier: Burlington, 2005.
  6. doi:10.1246/cl.1982.1559
    .
  7. doi:10.1021/ja01251a503
    .
  8. doi:10.1016/0040-4020(79)87010-6
    .
  9. doi:10.1021/jo01341a524
    .
  10. S2CID 197541600
    .
  11. doi:10.1021/jo00080a001
    .
  12. doi:10.1016/S0040-4039(00)61867-1
    .
  13. PMID 11672062
    .
  14. doi:10.1021/jo00203a036
    .
  15. doi:10.1021/jo00903a031
    .
  16. doi:10.1080/00397918808064009
    .
  17. PMID 14973617
    .
  18. doi:10.1021/jo00195a006
    .
  19. doi:10.1016/S0040-4039(00)83907-6
    .
  20. doi:10.1021/ja00255a076
    .
  21. doi:10.1016/S0040-4039(00)98737-9
    .
  22. doi:10.1246/cl.1984.1165
    .
  23. doi:10.1039/C39850000777
    .
  24. PMID 14507186
    .
  25. doi:10.1021/om00087a015
    .
  26. doi:10.1055/s-2008-1032023
    .
  27. ^
    PMID 16402826
    .
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