Polymethylhydrosiloxane (PMHS) as an Additive in Sonogashira Reactions

Abstract

Polymethylhydrosiloxane (PMHS) in combination with CsF facilitates the Sonogashira reaction of a variety of alkynes and electrophiles. These couplings appear to involve the in situ formation and reaction of an alkynylsiloxane. Such couplings can be run amine free at room temperature, reaction times are short, workup is easy, and product purification is straightforward. Thus, the advantages (and disadvantages) of running Sonogashira couplings with 1-silylalkynes are realized, without the need to preform the alkynyl silane.

Key words

Sonogashira reaction - enynes - alkynes - palladium - copper - cross-coupling

References

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4

Mori et al. (ref. [3i] [l] ) have found that using 1-silylalkynes in place of their parent 1-alkynes allows one to perform a Sonogashira reaction under neutral conditions with catalytic amounts of Pd(0) and Cu(I). Marshall et al. (ref. [3g] ) also reported a similar procedure, utilizing stoichiometric amounts of CuCl and 2 equiv of Bu₃N.

8

Couplings of 1 and 2 with 1.0 or 1.5 equiv of CuTC were lower yielding (44-68%).

11

CuCl could also be used, but the reaction yields tended to be slightly lower.

12

For the coupling of aryl or vinyl halides. The general procedure noted above (ref. [10] ) was followed except that 2 equiv of CuTC were used and the solvent was THF/NMP (1:1, 15 mL at 1.0 mmol scale).

13

Adding the alkyne, CsF, and PMHS at once caused rapid foaming that made monitoring by ReactIR™ difficult.