Alkyl Sonogashira cross-coupling

A%ne 25 undergoes a Sonogashira cross-coupling reaction v/ith the alkyl halide 26 under Pd(0) catalysis. 

The (o-aminoaryl)acetylenes 27 are easily accessible by Pd-mediated SONOGASHIRA cross coupling reactions of (o-halogeno)aniline derivatives 26 (X preferably I) with terminal acetylenes. Alternatively, 27 is prepared by Sonogashira coupling of 26 with TMS-acetylene (to give 29), desilylation of 29 and base-induced alkylation at the free acetylene terminus (29 29a -> 27). 

Recently, Fu has developed a catalyst for Sonogashira cross-couplings of unactivated primary alkyl bromides and iodides with an array of alkynes (Eq. 14)... 

Table 9 Sonogashira cross-couplings of primary alkyl bromides and iodides with alkynes...

Analogous intermolecular one-pot cascade transformation has been developed by Xi et al. [11b]. Consequently, a-bromoacrylates reacted with terminal acetylenes with the formation of densely substituted styrenes in a single transformation under Sonogashira cross-coupling reaction conditions (Scheme 14.14). This method was efficient for both aryl or alkyl acetylenes. Among vinyl bromides, only acrylate derivatives were shown to produce styrene derivatives in good yields. 

Many of the methods that have been reported for coupling alkyl electrophiles with terminal alkynes require a strong base and therefore have limited functional-group compatibility [35]. In contrast, the Sonogashira reaction, which is widely used to cross-couple aryl and vinyl electrophiles with terminal alkynes, employs a mild base (e.g., an amine). Expanding the scope of Sonogashira couplings to include alkyl electrophiles would be a welcome advance in alkyne chemistry. 

I 9 Cross-Coupling Reactions to sp Carbon Atoms Table 9.11 The Sonogashira coupling of alkyl halides under Ni catalysis [156]. 

The ring expansion of oxyglycal-derived gm-dihalo 1,2-cyclopropanate oxyglycals provides stable seven-membered halo-oxepines, that are thus suitable precursors for further functionalizations. In a study, vinyl bromide of the bromo-oxepine was used for the metal-catalyzed cross-coupling reactions, namely, Heck, Suzuki, and Sonogashira reactions, so as to generate 2-deoxy-2-C-alkyl/ary/alkynyl septanosides [33]. 

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