Alkenyl-Alkynyl Stille Coupling

Scheme 5.4.13 Alkenyl-alkynyl Stille couplings in the synthesis of different natural products (TBDMS tert-butyldlmethylsllyl)...

As organotin compounds (organostannanes) undergo smooth Pd-catalysed transmetallation, aryl halides react with a wide variety of aryl-, alkenyl- and alkylstannanes [139]. Coupling with allylstannane is the first example [140]. The reaction is called the Migita-Kosugi-Stille or Stille coupling. Aryl, alkenyl, allyl, alkynyl and benzyl... 

In comparison with the fabrication of alkynyl- or alkenyl-linked multicomponent assemblies, there are few examples dedicated to aryl-Pcs. Such attempts are mainly based on Suzuki or Stille couplings. Hence, Odobel et al. [80] reported the construction of a Pc macrocycle carrying a trimethyltin function, thus allowing... 

The Stille coupling uses a tin reagent (Bu3Sn-R) in which the R-group is commonly a vinyl species with an alkenyl, aryl, or alkynyl halide (often iodide or triflate) with palladium to give a new carbon-carbon bond. 

Palladium-catalyzed cross coupling of resin bound iodopyridine with a boronic acid (Suzuki reaction) (12) or with an alkenyl-, alkynyl-, or arylstannane (Stille reaction) (13) was effected by treatment of resin 5 with 4 equivalents of the boronic acid or stannane, 8 equivalents of K2CO3 (Suzuki reaction only), and catalytic Pd(PPh3)4 in DMF at 50 C for 20 hours. (14) Best results were achieved by running each reaction twice, with an intermediate wash of the resin, in order to drive the reaction to conq>letion. The corresponding Pd-catalyzed amination (Buchwald reaction) (15) worked well in protocol development but the reaction failed with the 3 amines attenpted during actual library preparation. 

Until recently, cross-coupling between alkylmetals and aryl, alkenyl, and alkynyl halides was achieved mostly with alkylcoppers. Over the past two decades, however, the Ni- or Pd-catalyzed reaction of alkylmetals with the unsaturated organic hahdes mentioned above has been developed as a viable alternative, as detailed in Sect. ni.2.II. The Cu-based methodology still remains highly competitive. So, it is advisable to consider both options for finding the method for a given case. 

AUcynylstannanes can cross-couple with a variety of other functional groups employing the Stille protocol. Couphng to acyl chlorides is a well-known procedure that affords aUcynylketones in respectable yields. Other reports include alkynyltin cross-couplings with a-haloethers and a-halocarbonyls, enol phosphinates and phosphonates, alkenyl(phenyl)iodonium salts, alkynyl halides, and allyl hahdes (Table 9.18). Alkynylstannanes have also been shown to cross-couple with iron halides under the Stille conditions to effectively form iron-carbon bonds. 

In contrast, the Stille reaction was one of the first cross-coupling reactions performed on solid support. For the palladium-catalyzed coupling of various aryl, vinyl, or alkynyl stannanes with aryl or alkenyl bromides, iodides, or triflates, the reaction conditions employed were chosen in analogy to the liquid phase procedures and often feature an arsine or trifurylphosphine as an added ligand. Due to the tedious separation of tin and organo tin reagents or by-products in solution phase, this carbon-carbon bondforming reaction is particularly suitable for solid-phase synthesis. ... 

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