The use of complex-forming solvents and variations in the reaction temperature made it possible to prepare c~-halogeno ~3-hydroxy carboxylic esters upon addition of haloger~oacetic esters to aldehydes and ketones promoted by iron pentacarbonyl.Key words: Reformatsky reaction, iron pentacarbonyl, halogenoacetic esters, aldehydes. ketones, addition reaction.Recently, considerable attention has been given to the development of new synthetic procedures for the formation of C--C bonds using reactions involving metals or their compounds in which the metals are in the lowest valence state. In this case, the addition reactions at the multiple bonds, in particular, at the C=C and C=O bonds, are of great importance.Considerable advances in this field have been made owing to the use of Smi 2 as the reagent in combination with particular solvents and additives. I Previously, we have demonstrated for the first time that iron pentacarbonyl is an efficient promoter of the Rcformatskytype addition of c~-halogeno carboxylic esters to aldehydes and ketones, z,3 In these reactions, CBrCI 3, Br 2. or 12 was used as the activating agent (see Ref.3).As part of our continuing studies, in the present work we investigated the effects of the temperature and the nature of the solvent on the course of the reaction.It is known 4 that complex-forming solvents favor the Reformatsky-type addition under milder conditions and improve the selectivity of the processes. It is also significant that under the conditions which we have originally used (i.e., in boiling benzene), methyl bromoacetate (1) did not enter into the reaction and polyhalogenoacetic esters reacted with aldehydes and ketones to form acrylic acid derivatives without intermediate formation of esters of hydroxy acids.We found that the addition of bromoester ! to benzaldehyde (2a) and butyl methyl ketone (2b) yielding esters of 13-hydroxy acids 3a,b proceeded rather successfully only at 130 ~ (boiling in chlorobenzene). The structures of products 3a,b were confirmed by spectral methods.Among the products of the reaction with benzaldehyde. methyl cinnamate was identified by GLC-mass spectrometry, which is additional evidence for the structure of hydroxy ester 3a. The reaction with butyl methyl ketone yielded products of aldol and crotonic condensation. which were detected in the reaction mixture by GLC-mass spectrometry, along with ester 3b. The reactions of trichloro-and dibromoacetic esters with compounds 2a,b in DMF or HMPA at ~20~ afforded esters of 13-hydroxy acids as the major products. These reactions did not proceed in other solvents (benzene, THF, or DMSO) at ~20~The reaction of methyl trichloroacetate (4) with benzaldehyde (2a) in DMF carried out at room temperature over 3 days afforded methyl 2,2-dichloro-3-hydroxy-3-phenylpropionate (5) and methyl 2-chloro-3-phenylacrylate (in a ratio of 4:1), whereas this reaction in HMPA gave dimethyl tetrachlorosuccinate (6) (Scheme 2).
Scheme 2CClsCOOMe + PhCHO ~ PhCH(OH)CCI2COOMe 4 2a ~ 5 MeOOCCCI2CCI~COOMe 6Reagents and conditions: a....
