Synthesis Reformatsky

REFORMATSKY BLAISE Zincahyiallon Synthesis of -hydrexyesters from cartxinyl derivatives arxl a-haloesters via a zmc reagent (Reformatsky). Synthesis ol eloesleis from nitriles and a-haloesters via a zinc reagent (QIaise). 

Synthesis of p-hydroxyesters from carbonyl derivatives and a-halo esters via a zinc reagent (Reformatsky). Synthesis of p-ketoesters from nitriles and a-halo esters via a zinc reagent (Blaise) (see 1st edition). 

A reaction of preparative importance, involving zinc, is the Reformatsky synthesis,212 in which this metal causes an oc-halo ester to react with a carbonyl compound. It is analogous to the Grignard reaction ... 

The synthesis of rrani-[13- C]retinoic acid (265) (Procedure B) may serve as an additional example of the use of an [ " C]acetone-based building block. Homer-Wads-worth-Emmons olefination of [2- C]acetone with methyl diethyl-phosphonoacetate afforded methyl 3-methyl-2-[3- C]butenoate t2631. Upon deprotonation, this coupled with /3-ionylideneacetaldehyde (264) to provide 265. thereby extending the carbon skeleton of 264 again by a labeled five-carbon unit Building block 263 was also shown to be accessible (Procedure C) through Reformatsky synthesis of [2- C]acetone with zinc and... 

Synthesis Control will be needed in the condensation as the ketone C is more reacfiye than the acid D both in enolisation and electrophilic power. The Reformatsky looks a good method. Again we don t know how this commercial product is actually made ... 

Beckmann rearrangement, 3, 710 Pyran-4-carbaldehyde, 2,2-dimethyl-tetrahydro-Reformatsky reaction, 3, 732 4H-Pyran-4-carbaldehydes synthesis, 3, 760-761 Pyran-2-carbonitrile, 5,6-dihydro-reactions, 3, 732... 

Because of the mild reaction conditions, and its broad applicability, the Knoevenagel reaction is an important method for the synthesis of a ,/3-unsaturated carboxylic acids. Comparable methods are the Reformatsky reaction, the Perkin reaction, as well as the Claisen ester condensation. The Knoevenagel reaction is of greater versatility however the Reformatsky reaction permits the preparation of a ,/3-unsaturated carboxylic acids that are branched in a-position. 

The indium-mediated aqueous Reformatsky reaction was used in the synthesis of a,a-difluoro- 3-hydroxy ketones (Eq. 8.93).236... 

A similar sequence starting with the acylation product (76) from metachlorophenylacetonitrile gives the halogenated tricyclic ketone 83. Condensation of that intermediate with ethyl bromoacetate in the presence of zinc (Reformatsky reaction) gives the hydroxyester 84. This product is then in turn dehydrated under acid conditions (85), saponified to the corresponding acid (86), and converted to the dimethyl-amide (87) by way of the acid chloride. The amide function is then reduced to the amine (88) with lithium aluminum hydride catalytic hydrogenation of the exocyclic double bond completes the synthesis of closiramine (89). This compound also exhibits antihistaminic activity. 

R,4R)-Supellapyrone (41) is the female sex pheromone of the brown banded cockroach (Supella longipalpa). Scheme 59 summarizes Mori s synthesis of 41 [89].Enzymatic desymmetrization of meso-B to give (2R,4S)-C and Reformatsky-type cyclization of D to furnish E were the key steps. 

The synthesis of (3S,4R)-4-(l-aminocycloprop-l-yl)-3-fluoropyrrolidine (28) is illustrated in Schemes 9 and 10. Namely, Reformatsky reaction of 1-acetylcyclopropanecarboxylate (32) [28] with ethyl bromoacetate yields the hydroxyester intermediate (33). Chlorination of this intermediate with... 

As a kind of nucleophilic addition reaction similar to the Grignard reaction, the Reformatsky reaction can afford useful ft-hydroxy esters from alkyl haloacetate, zinc, and aldehydes or ketones. Indeed, this reaction may complement the aldol reaction for asymmetric synthesis of //-hydroxy esters. 

A furanose-fused c/.,(3-unsaturated 8-lactone was also prepared from ester 11 as a key chiral intermediate for the synthesis of the enantiomer of (+ )altholactone, a natural product with cytotoxic and antitumor activities.18 A Reformatsky reaction with ethylbromoacetate or a Wittig... 

Nucleophilic additions to (cyclohexadienone)Fe(CO)3 complexes (218) occur in a dia-stereospecific fashion (Scheme 56)197. For example, the Reformatsky reaction of ketone (218a) affords a simple diasteromeric alcohol product19715. The reduction of (1-carbo-methoxycyclohexa-l,3-dien-5-one)Fe(CO)3 (218b) to give 219 has been utilized in the enantioselective synthesis of methyl shikimate. In a similar fashion, cycloadditions of (2-methoxy-5-methylenecyclohexa-l,3-diene)Fe(CO)3 (220) occur in a diastereospecific fashion198. 

---