Halides acetylenic, reduction

The majority of preparative methods which have been used for obtaining cyclopropane derivatives involve carbene addition to an olefmic bond, if acetylenes are used in the reaction, cyclopropenes are obtained. Heteroatom-substituted or vinyl cydopropanes come from alkenyl bromides or enol acetates (A. de Meijere, 1979 E. J. Corey, 1975 B E. Wenkert, 1970 A). The carbenes needed for cyclopropane syntheses can be obtained in situ by a-elimination of hydrogen halides with strong bases (R. Kdstcr, 1971 E.J. Corey, 1975 B), by copper catalyzed decomposition of diazo compounds (E. Wenkert, 1970 A S.D. Burke, 1979 N.J. Turro, 1966), or by reductive elimination of iodine from gem-diiodides (J. Nishimura, 1969 D. Wen-disch, 1971 J.M. Denis, 1972 H.E. Simmons, 1973 C. Girard, 1974),... 

Sonogashira has proposed a catalytic cycle (Figure 4) which shows 1) the reduction of the palladium complex, 2) coordination of the aryl halide and acetylene with the palladium (0) complex and 3) the reductive elimination of the substituted aryl acetylene and regeneration of the active catalyst.(10)... 

Several publications deal with acetylenic halides that can undergo reductive intramolecular cyclization [37]. For example, electrolysis of 6-iodo-l-phenyl-l-hexyne at a carbon cathode gives benzylidenecy-clopentane in 36% yield. 

Chromium(II) sulfate is a versatile reagent for the mild reduction of a variety of bonds. Thus aqueous dimethylformamide solutions of this reagent at room temperature couple benzylic halides, reduce aliphatic monohalides to alkanes, convert vicinal dihalides to olefins, convert geminal halides to carben-oids, reduce acetylenes to /raw5-olefins, and reduce a,j3-unsatu-rated esters, acids, and nitriles to the corresponding saturated derivatives. These conditions also reduce aldehydes to alcohols. The reduction of diethyl fumarate described in this preparation illustrates the mildness of the reaction conditions for the reduction of acetylenes and o ,j8-unsaturated esters, acids, and nitriles. 

Kleinman and co-workers 20 synthesized a lactone precursor to the (2/ ,46, 56 )- -hydroxy-ethylene dipeptide stereoselectively in four steps using the lithium salt of ethyl propiolate as a homoenolate equivalent. As summarized in Scheme 11, addition of ethyl lithiopropiolate to a protected a-amino aldehyde affords hydroxy acetylenic esters as a mixture of dia-stereomers. Reduction of the acetylene group and subsequent lactonization gives a readily separable (4S)-lactone-enriched mixture. Direct alkylation with alkyl halide and lithium hexamethyldisilanazide yields the tram-lactone as the major stereoisomer. 

A particularly simple variation of this reaction has been developed (47, 48) in which the catalytic nickel species is formed in situ by reduction of nickel chloride with a manganese -iron alloy in the presence of thiourea. Allyl halide is added and at the same time acetylene and carbon monoxide are bubbled through the methanolic solution. Conversion is almost complete and yields of ar-methyl-2,5-dienoate of up to 80% have been claimed. 

In the presence of anhydrous Cr(II) halide salts, organic halides undergo one-electron reduction to form radical species, which in the presence of a second equivalent of Cr(II) undergo a second one-electron reduction to form organochromium(III) species (Scheme 5)331. This process works well for allyl, vinyl and acetylenic halides, but not for simple alkyl cases. Alkylchromium(III) species can be formed readily, however, in the presence of catalytic amounts of vitamin B12 or cobalt phthalocyanine (CoPc)332. 

Mauret and Alphonse reported that a finely divided nickel prepared by reduction of nickel halide with magnesium in ethanol was more selective for semihydrogenation of both mono- and disubstituted acetylenes than Raney Ni or those obtained by reduction in THF.86 With the nickel produced in ethanol, the rate of hydrogen uptake after 1 equiv was almost nil in the case of 3-hexyne, and 98-99% of cA-3-hexene along with only 1-2% of hexane was produced. 

The electroreductive cyclization of some acetylenic halides in DMF has been reported by Moore and Peters. 6-Bromo-l-phenyl-l-hexyne (3) gave three polarographic waves at —2-35 V, —2-60 V and — 2-80 V (vs. S.C.E.). The first wave was correlated with C-Br fission ( -hexyl bromide was reduced at —2-29 V) while the two remaining waves corresponded to triple bond reduction (1-phenyl-1-hexyne gave waves at —2-65 V and —2-88 V). The electrolysis reaction mixture contained both five- and six-membered carbocycles as well as straight-chain reduction products... 

Table 4). The formation of the six-membered ring compounds is unique to the electrochemical method, since chemical reduction of the acetylenic halide by, for example, butyllithium yields solely benzylidene cyclopentane (4). It was suggested ... 

Scheme 5-3 Pd-catalyzed cross-coupling reaction of terminal acetylenes with sp- halides i, oxidative addition ii, transmetallation iii, reductive elimination.

Several investigations [112-115] have dealt with acetylenic halides that undergo reductive intramolecular cyclization. In DMF containing tetraalkylammonium perchlorates, elec-... 

The linear connection [3] between the reduction potential of N,N-dimethylhydra-zones and their rate of cleavage [vide infra] supports the analogy with the reduction of vinylic halides. The analogy is further substantiated by the fact that vinyl halides of the type RCH=CR"Y form acetylenic compounds RC=CR" by a base-induced elimination on reduction in aprotic medium [2], analogously to the formation of nitriles from RCH= NY under similar conditions [4]. 

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