Reformatsky reaction Subject

More recently, a pulsed sonoelectrochemical technique was developed to produce a suspension of fine Zn powder which can be directly used in Reformatsky reactions ZnCl2 and NH4C1 (supporting electrolyte) in diluted HC1 are subjected to a pulsed electrical current (current density = 104 Am-2 pulse duration = 300 ms) and to ultrasound for 1 h54. 

The reaction has been studied by many workers. A review (447) covers the literature on this subject up to and including 1960, and the present work covers the years 1961-1972. This type of reaction with y-halo-a,j3-unsaturated esters is included in the reviews on the Reformatsky reaction. 

Interest has been expressed by the People s Republic of China in the preparation of cephalotaxine ester alkaloids and analogues, no doubt for the purpose of evaluation of antitumour activity. Thus a number of esters, e.g. (34), (R = Me2CHCH2CH2COCO or PhCOCO), were subjected to Reformatsky reaction with methyl bromoacetate to give, e.g., [34 R = Me2CHCH2CH2C(OH)-(CH2C02Me)C0] (deoxyharringtonine) and [34 R = PhC(0H)(CH2C02Me)C0]. 

Bioactive compounds that contain the difluoromethylene group adjacent to the carbonyl functionality have been the subject of increased research efforts in recent yearsf 59). The most widely utilized methods that have been employed to introduce this group into organic molecules have been (a) Reformatsky reaction of halodifluoroacetates (60-66) (b) elaboration of difluoroketene silyl acetals (67-69) (c) metal catalyzed addition of 3-bromo-3,3-difluoropropene to aldehydes and ketones (70) and (d) alkylation of CuCF2COOR(77). The modest yields associated with these methods prompted us to explore alternative methodology for the preparation of this useful building block. 

The retinaldehydes (484) and (485), which carry a trifluoromethyl group at C-9, were obtained from the C15 acid (483) by a standard procedure (Asato et aL, 1982). The 9 acid (483) (carotenoid numbering scheme) was formed when the pyrone (482) was subjected to a stereospecific ring-opening reaction. Tyrone (482) was prepared from p-cyclocitral (480) by a Reformatsky reaction, using the C5 unit (481). 

A case in point is cyclohexane-1,3-dione. This may be converted into a mono-dioxolan [227, 228], or into a mono-dithiolem or -oxathiolan [228]. The dioxolan is partially cleaved to the hydroxyethyl enol ether (with which it is in thermal equilibrium) by very dilute base, and it reverts to the diketone under more strongly alkaline conditions [227]. The free ketone group in these ketals can be made to react vtith various nucleophilic reagents such as phenyl lithium [228] and cyanide ion [227] and can also be subjected to the Reformatski reaction [227], but the yields in these reactions appear to be rather low. 

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