Coupling reactions of alkynylsilanes

N. Sakai, N. Uchida, T. Konakahara, Synlett 2008, 1515-1519. Facile and selective synthesis of propargylic amines and 1,6-diynes one-pot three-component coupling reactions of alkynylsilanes, aldehydes and amines by a cooperative catalytic system comprised of CuCl and Cu(OTf)j. 

A useful alternative under neutral conditions is the coupling reaction of alkynylsilanes with aryl- (or alkenyl-) triflates using a CuCl/Pd cocatalyst system (eq 18). For the mechanistic pathway the authors presume that a transmetalation from silicon to copper takes place as the keystep (Cul being less effective in the transmetalation), allowing the synthesis of symmetrical and un-symmetrical arylalk)mes. 

Synthetic reactions involving activation of alkenyl- and arylsilanes by copper salts have also been reported. A copper-mediated system is effective in the cross-coupling reaction of aryl- and heteroarylsilanes with aryl halides under Pd-free conditions (Equation (13)).66 Alkenyl- and arylsilanes as well as alkynylsilanes undergo homocoupling in the presence of Cul and air.65,65a Functionalized alkenyl- and arylsilanes bearing a coordination site in the vicinity of silicon (e.g., 7) are easily activated by copper salts even at room temperature (Scheme 5).67,67l 67e 68 q-jle organocoppers such as 8 are useful for carbon-carbon bond-forming reaction with carbon electrophiles. 

Alkynyltrimethylsilanes act as effective alkynyl donors in the presence of a fluoride ion source [15]. Recent studies on the Sonogashira-type reaction of alkynylsilanes have revealed that the use of a Cu(I) [554] or Ag(I) [555] salt leads to highly efficient coupling with vinyl and aryl triflates (Scheme 10.213). 

Hiyama and Mori have reported that homo-coupling reactions of vinyl-, aryl-, and alkynylsilanes are effectively promoted by an equimolar amount of CuCl and air (Scheme 10.218) [565]. The reaction mechanism probably involves formation of organocopper species by Si-Cu transmetalation and subsequent oxidative dimerization by air. The strong tendency of CuCl to activate alkynylsilanes has been used for coupling reactions with 1-chloroalkynes (Scheme 10.218) [566]. 

Another application of [Bu4N][Ph3SiF2] 826 involves the silicon-carbon bond cleavage of allyl-, benzyl-, and alkynylsilane derivatives 827-829.826 Subsequent reactions of the generated carbanions with electrophiles (Scheme 112) and alkyl halides (Scheme 113) provide high yields of carbon-carbon coupled products. 

TMS group is used for protection of terminal alkynes. However, alkynylsilanes themselves can be used for the coupling with aryl and alkenyl triflates using Pd-CuCl as a catalyst [74], Thus the internal alkyne 160 is prepared by stepwise reactions of two different triflates 157 and 159 with trimethylsilylacetylene (134) via 158. 

Alkynylsilanes can be converted into alkynylcoppers by treatment with Cu salts in an aprotic polar solvent such as l,3-dimethyl-2-imidazolidinone (DMI).62 The Cu-promoted coupling reactions via the Si-Cu transmetallation of alkynylsilanes are valuable for the syntheses of alkynyl ketones, 1,3-diynes, 1,3-enynes, and 1-aryl-l-alkynes from acid chlorides,62 alkynyl chlorides,63 alkenyl iodides,64 and aryl iodides,64 respectively (Equation (12)). In addition, symmetric 1,3-diynes can be prepared by the CuCl-mediated homocoupling of alkynylsilanes.65 653... 

A catalytic amount of CuCl was found to activate alkynyl(trimethyl)silanes in the palladium-catalyzed coupling reaction with aryl triflates (Eq. 7) [12]. The catalytic cycle is considered to involve the transfer of an alkynyl group from an alkynylsilane to Cu(I) and then to palladium(II). A sequential palladium-catalyzed reaction of trimethylsilylacetylene gives unsymmetrical diarylacet-ylenes (Eq. 8). 

Successful extensions to sp-carbon cross-coupling reactions with vinyl triflates are exemplified by the synthesis of the enyne 32 [Eq, (15)]. It is noteworthy that this reaction is compatible with the presence of alkynylsilanes, emphasizing the different behavior of organosilicone and organotin derivatives [25]. 

We have found that alkynylsilanes are smoothly converted into alkynylcopper compounds by treatment with CuCl in l,3-dimethyl-2-imidazohdinone (DMI) the copper reagents can be isolated in good yields [563]. This study was the first example of preparation and isolation of organocopper compounds by use of organosilicon reagents. The Si-Cu transmetalation is applicable to the synthesis of alkynyl ketones by Cu-catalyzed alkynylation of acid chlorides (Scheme 10.217). We have also shown that a Cu-mediated system is effective in the cross-coupling reaction between arylsilanes or heteroarylsilanes and aryl hahdes [564]. 

The reaction of optically active allyl(difluoro)phenylsilanes with aryl triflates affords optically active allylarenes with high stereoselectivities, wherein the absolute configuration of the newly generated chiral carbon can be controlled by the choice of a fluoride salt and the solvent polarity (Scheme 29). Aryl and alkenyl triflates are effective coupling partners not only for aUylsilanes but also for alkenyl-, aryl-, alkyl-, and alkynylsilanes as we have been seen in some examples of the preceding sections. 

Significantly higher yields were, however, achieved in the absence of a Pd catalyst for this procedure and hence sparked interest in Pd-free variants of the sila-Sonogashira-Hagihara reaction. A simple, but efficient system used the inexpensive and readily available CuCl/PPhj combination for the catalytic cross-coupling of alkynylsilanes with aryl iodides [322]. 

Alkyne replacements have also been reported. In 2008, Sakai et al. described the use of alkynylsilanes instead of terminal alkynes in the Cu-catalyzed synthesis of propargyl-amines, which was applicable to both secondary and primary aliphatic amines, although the latter afforded the corresponding products in low yield [145]. Very recently. Van der Eycken et al. applied the A -coupling to the C—H alkylation of azoles through a copper-catalyzed hetero-arene-amine-aldehyde/ketone coupling [146]. This reaction is proposed to proceed through the initial condensation of... 

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