Reformatzky reaction

Reformatzky reaction of 52 followed by radical-initiated reductive hydrogenation of the hydroxyl group in 58 via a thiocarbamate intermediate provides 59. The usual chemical modification of 59 produces enantiomerically pure 4,4-difluoroglutamine 60 (see Scheme 15) [33]. 

Reformatzki Reactions with y-Methylbromothio-acetate. Recueil Trav. 

It is usually unnecessary to use a solvent in such reactions, but one is sometimes used so that the product is obtained in solution. Ethyl acetate, often in admixture with toluene, is the solvent of choice since it accelerates the reaction appreciably. Diethyl ether can also be used, although it does not increase the rate of reaction and in some cases a little iodine must then be added to start the reaction. When higher reaction temperatures are necessary, diisopropyl or dibutyl ether is used139 (in this connexion see the Reformatzky reaction, page 884). 

Grignard Reagents 497 Organolithium Compounds 509 Reformatzky Reactions 511... 

The first synthesis of a jasmonoid, namely dihydrojasmone, took place nine years before the structure of jasmone itself was established. This goal was achieved in 1924 by Hermann Staudinger and Leopold Ru icika in the course of their work on pyrethroids. [84] They carried out a Reformatzky reaction between ethyl laevulinate and ethyl 2-bromoheptanoate, and obtained the desired product, although in poor yield, by a Dieckmann cyclisation, followed by hydrolysis and decarbethoxylation (see next page). 

An improved variant uses a bromopropionamide for the construction of the side-chain carboxylic acid this amide is simply accessible in two stages from cyclohexanone, salicylamide and bromopropionyl bromide. Then follows a Reformatzky reaction with remarkable diastereoselectivity under formal retention of the absolute configuration. [61] Chromatographic purification is not necessary. 

Almost 10 years after and independent of Inhoffens pioneering research, Karl Miescher (1892-1974) and George Anner from Ciba AG in Basel published in 1948 the first total synthesis of enantiopure (+)-oestrone. [32] Their approach was based on earlier work from Robert Robinson (1886-1975) in Oxford and Werner Emmanuel Bachmann (1901-1951) in Ann Arbor, Michigan. As another highlight in steroid chemistry, their synthesis stands out as one of the earliest attempts to circumvent the challenging demethylation step. Key reaction sequences are a malonic ester synthesis, a Dieckmarm cychsation, a Reformatzky reaction and the application of the Arndt-Eistert reaction. Remarkable is here as well the high art of crystallisation In the first fractional crystallisation, three racemic diastereomers were separated and in the second one two. Finally, enantiopure (+)-oestrone is obtained by stereoselective crystallisation of the desired diastereomer of the ((-)-menthyloxy) acetate. 

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