The Reformatsky reaction (sometimes misspelled Reformatskii reaction) is an
organic reaction
Organic reactions are chemical reactions involving organic compounds. The basic organic chemistry reaction types are addition reactions, elimination reactions, substitution reactions, pericyclic reactions, rearrangement reactions, Mechanistic Organ ...
which
condenses aldehydes or
ketone
In organic chemistry, a ketone is a functional group with the structure R–C(=O)–R', where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group –C(=O)– (which contains a carbon-oxygen double bo ...
s with α-halo
esters using metallic
zinc to form β-hydroxy-esters:
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.
In addition
to aldehydes and ketones, it has also been shown that the Reformatsky enolate is able to react with
acid chlorides
In organic chemistry, an acyl chloride (or acid chloride) is an organic compound with the functional group . Their formula is usually written , where R is a side chain. They are reactive derivatives of carboxylic acids (). A specific example ...
,
imines,
nitriles (see
Blaise reaction), and
nitrones. Moreover,
metals other than zinc have also been used, including
magnesium,
iron,
,
nickel,
germanium
Germanium is a chemical element with the symbol Ge and atomic number 32. It is lustrous, hard-brittle, grayish-white and similar in appearance to silicon. It is a metalloid in the carbon group that is chemically similar to its group neighbors s ...
,
cadmium,
indium,
barium
Barium is a chemical element with the symbol Ba and atomic number 56. It is the fifth element in group 2 and is a soft, silvery alkaline earth metal. Because of its high chemical reactivity, barium is never found in nature as a free element.
Th ...
, and
cerium.
Additionally,
metal salts are also applicable in place of metals, notably
samarium(II) iodide,
chromium(II) chloride,
titanium(II) chloride, cerium(III) halides such as
cerium(III) iodide
Cerium(III) iodide (CeI3) is the compound formed by cerium(III) cations and iodide
An iodide ion is the ion I−. Compounds with iodine in formal oxidation state −1 are called iodides. In everyday life, iodide is most commonly encountered a ...
, and
titanocene(III) chloride.
Structure of the reagent
The crystal structures of the
THF complexes of the Reformatsky reagents ''tert''-butyl bromozincacetate and ethyl bromozincacetate
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''.
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.
[Kurti, L.; Czako, B. ''Strategic Applications of Named Reactions in Organic Synthesis''; Elsevier: Burlington, 2005.]
Variations
In one variation of the Reformatsky reaction
an
iodolactam is coupled with an
aldehyde with
triethylborane in
toluene at -78 °C.
See also
*
Aldol reaction
*
Blaise reaction
*
Claisen condensation
* Example use in total synthesis:
Mukaiyama Taxol total synthesis (B ring construction)
References
{{reflist
Addition reactions
Carbon-carbon bond forming reactions
Organometallic chemistry
Name reactions