Global InformationReformatsky reaction information
| 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 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[5] to aldehydes and ketones, it has also been shown that the Reformatsky enolate is able to react with acid chlorides,[6] imines,[7] nitriles (see Blaise reaction), and 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]
- ^ 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.
- ^ Reformatsky, S. (1890). "Action of zinc and ethyl chloroacetate on ketones and aldehydes". J. Russ. Phys. Chem. Soc. 22: 44.
- ^ Shriner, R. L. (1942). "The Reformatsky Reaction". Organic Reactions. 1: 1–37. doi:10.1002/0471264180.or001.01. ISBN 9780471264187.
- ^ Rathke, M. W. (1975). "The Reformatsky Reaction". Organic Reactions. 22: 423–460. doi:10.1002/0471264180.or022.04. ISBN 0471264180.
- ^ a b c Cite error: The named reference
Kurtiwas invoked but never defined (see the help page). - ^ Sato, Toshio; Itoh, Toshiyuki; Fujisawa, Tamotsu (1982). "Facile synthesis of β-ketoesters by a coupling reaction of the Reformatsky reagent with acyl chlorides catalyzed by a palladium complex". Chemistry Letters. 11 (10): 1559–1560. doi:10.1246/cl.1982.1559.
- ^ Gilman, Henry; Speeter, Merrill (1943). "The Reformatsky Reaction with Benzalaniline". Journal of the American Chemical Society. 65 (11): 2255–2256. doi:10.1021/ja01251a503.
- ^ Stamm, H.; Steudle, H. (1979). "Nitrone—XI Isoxazolidin-verbindungen—VIII : N-substituierte 5-isoxazolidinone durch reformatzky-reaktion mit nitronen". Tetrahedron. 35 (5): 647–650. doi:10.1016/0040-4020(79)87010-6.
- ^ Moriwake, Tosio (1966). "The Reformatsky Reaction. I. Condensation of Ketones and t-Butyl Bromoacetate by Magnesium". The Journal of Organic Chemistry. 31 (3): 983–985. doi:10.1021/jo01341a524.
- ^ Liu, Xuan-Yu; Li, Xiang-Rui; Zhang, Chen; Chu, Xue-Qiang; Rao, Weidong; Loh, Teck-Peng; Shen, Zhi-Liang (2019). "Iron(0)-Mediated Reformatsky Reaction for the Synthesis of β-Hydroxyl Carbonyl Compounds". Organic Letters. 21 (15): 5873–5878. doi:10.1021/acs.orglett.9b01999. PMID 31318222. S2CID 197541600.
- ^ Orsini, Fulvia; Pelizzoni, Francesca; Pulici, Maurizio; Vallarino, Lidia M. (1994). "A cobalt-phosphine complex as mediator in the formation of carbon-carbon bonds". The Journal of Organic Chemistry. 59 (1): 1–3. doi:10.1021/jo00080a001.
- ^ Inaba, Shin-ichi; Rieke, Reuben D. (1985). "Reformatsky type additions of haloacetonitriles to aldehydes mediated by metallic nickel". Tetrahedron Letters. 26 (2): 155–156. doi:10.1016/S0040-4039(00)61867-1.
- ^ Kagoshima, Hirotaka; Hashimoto, Yukihiko; Oguro, Dai; Saigo, Kazuhiko (1998). "An Activated Germanium Metal-Promoted, Highly Diastereoselective Reformatsky Reaction". The Journal of Organic Chemistry. 63 (3): 691–697. doi:10.1021/jo971672j. PMID 11672062.
- ^ Burkhardt, Elizabeth R.; Rieke, Reuben D. (1985). "The direct preparation of organocadmium compounds from highly reactive cadmium metal powders". The Journal of Organic Chemistry. 50 (3): 416–417. doi:10.1021/jo00203a036.
- ^ Chao, Li-Chung; Rieke, Reuben D. (1975). "Activated metals. IX. New reformatsky reagent involving activated indium for the preparation of β-hydroxy esters". The Journal of Organic Chemistry. 40 (15): 2253–2255. doi:10.1021/jo00903a031.
- ^ Araki, Shuki; Ito, Hirokazu; Butsugan, Yasuo (1988). "Synthesis of β-Hydroxyesters by Reformatsky Reaction Using Indium Metal". Synthetic Communications. 18 (4): 453–458. doi:10.1080/00397918808064009.
- ^ Yanagisawa, Akira; Takahashi, Hiroshi; Arai, Takayoshi (2004). "Reactive barium-promoted Reformatsky-type reaction of α-chloroketones with aldehydes". Chemical Communications (5): 580–581. doi:10.1039/B314752P. PMID 14973617.
- ^ Imamoto, Tsuneo; Kusumoto, Tetsuo; Tawarayama, Yoshinori; Sugiura, Yasushi; Mita, Takeshi; Hatanaka, Yasuo; Yokoyama, Masataka (1984). "Carbon-carbon bond-forming reactions using cerium metal or organocerium(III) reagents". The Journal of Organic Chemistry. 49 (21): 3904–3912. doi:10.1021/jo00195a006.
- ^ Tabuchi, Takanori; Kawamura, Kisa; Inanaga, Junji; Yamaguchi, Masaru (1986). "Preparation of medium- and large-ring lactones. SmI2-induced cyclization of ω-(α-bromoacyloxy) aldehydes". Tetrahedron Letters. 27 (33): 3889–3890. doi:10.1016/S0040-4039(00)83907-6.
- ^ Molander, Gary A.; Etter, Jeffrey B. (1987). "Lanthanides in organic synthesis. 8. 1.3-Asymmetric induction in intramolecular Reformatskii-type reactions promoted by samarium diiodide". Journal of the American Chemical Society. 109 (21): 6556–6558. doi:10.1021/ja00255a076.
- ^ Dubois, Jacques-Emile; Axiotis, Georges; Bertounesque, Emmanuel (1985). "Chromium (II) chloride : a new reagent for cross-aldol reactions". Tetrahedron Letters. 26 (36): 4371–4372. doi:10.1016/S0040-4039(00)98737-9.
- ^ Ishihara, Takashi; Yamanaka, Tohru; Ando, Teiichi (1984). "New low-valent titanium catalyzed reaction of chlorodifluoromethyl ketones leading to α,α-difluorinated β-hydroxy ketones". Chemistry Letters. 13 (7): 1165–1168. doi:10.1246/cl.1984.1165.
- ^ Fukuzawa, Shin-Ichi; Fujinami, Tatsuo; Sakai, Shizuyoshi (1985). "Carbon–carbon bond formation between α-halogenoketones and aldehydes promoted by cerium(III) iodide or cerium(III) chloride–sodium iodide". Journal of the Chemical Society, Chemical Communications (12): 777–778. doi:10.1039/C39850000777.
- ^ Parrish, J. D.; Shelton, Daniel R.; Little, R. Daniel (2003). "Titanocene(III)-Promoted Reformatsky Additions". Organic Letters. 5 (20): 3615–3617. doi:10.1021/ol035269c. PMID 14507186.