Copper iodide-Dimethyl sulfide

The beneficial effect of added phosphine on the chemo- and stereoselectivity of the Sn2 substitution of propargyl oxiranes is demonstrated in the reaction of substrate 27 with lithium dimethylcyanocuprate in diethyl ether (Scheme 2.9). In the absence of the phosphine ligand, reduction of the substrate prevailed and attempts to shift the product ratio in favor of 29 by addition of methyl iodide (which should alkylate the presumable intermediate 24 [8k]) had almost no effect. In contrast, the desired substitution product 29 was formed with good chemo- and anti-stereoselectivity when tri-n-butylphosphine was present in the reaction mixture [25, 31]. Interestingly, this effect is strongly solvent dependent, since a complex product mixture was formed when THF was used instead of diethyl ether. With sulfur-containing copper sources such as copper bromide-dimethyl sulfide complex or copper 2-thiophenecarboxylate, however, addition of the phosphine caused the opposite effect, i.e. exclusive formation of the reduced allene 28. Hence the course and outcome of the SN2 substitution show a rather complex dependence on the reaction partners and conditions, which needs to be further elucidated. 

A neat combination of some of the foregoing chemistiy is use of the cyclic stannane (48) as an equivalent of the 1,4-pentadienyl dianion (49). Thus, treatment of the stannane (48) with Bu"Li, copper(I) iodide-dimethyl sulfide complex and the iodoallene (50) smoothly leads to the dienyne (51) and thence, by a repetition of this sequence but using electrophile (52), to 3-dehydroarachidonic acid methyl ester (53). 

A modification of this general procedure was used in the synthesis of (prop-2-enylidene)cyclo-propane (allylidenecyclopropane, 12).Allyl bromide was first alkylated in 81 -90% yield with l-lithio-l-(phenylsulfanyl)cyclopropane (10) in the presence of copper(I) iodide or cop-per(I) iodide-dimethyl sulfide. The adduct was then methylated with methyl fluorosulfonate or with dimethyl sulfate, and the sulfonium salt cleaved with powdered potassium hydroxide in dimethyl sulfoxide, to give the product in 50-70% overall yield for the second step. 

Vinyl halides. The method of Normant et al. (6, 270) for preparation of vinylcopper compounds can be used to obtain vinyl halides. Reaction of 1 with iodine gives vinyl iodides directly, but this reaction when extended to Bf2 or CI2 gives mainly dimers. The desired vinyl chlorides and bromides canTte obtained with NCS or NBS in fair to good yields. The replacement occurs with retention of initial stereochemistry. The American group also stresses the importance of the purity of the copper salt and uses House s cuprous bromide complex with dimethyl sulfide (6, 270). 

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