Stille cross coupling Synthesis applications

The constrnction of the dragmacidin E core ring system 107 proceeds via two Stille cross-couplings with A-tosyl-3-(tri-n-butylstannyl)-indole and 105 (Scheme 5.4.20).This synthesis also features an application of a new indole annnlation reaction.99... 

Despite growing importance of axially chiral biaryls as chiral auxiliaries in asymmetric synthesis, direct synthetic methods accessing to the enantiomerically enriched biaryls from achiral precursors are still very rare, Application of asymmetric cross-coupling to construction of the chiral biaryls is one of the most exciting strategies to this goal. The reported application... 

The preparation of amphimedine 7-46 published by Echavarren and Stille [512] is a noteworthy application of 2-aza-1,3-butadienes in natural product synthesis since it is an interesting combination of hetero Diels-Alder methodology with a palladium catalysed cross coupling. Thus, dienophile 7-44 was formed by Stille coupling of the triflate 7-42 with the stannyl aniline 7-43. This qui-none then underwent cycloaddition to the 2-aza-l,3-butadiene 7-45 an acid catalysed hydrolysis of the cycloadduct 7-47 and subsequent N-methylation completed the synthesis of amphimedine 7-46 (Fig. 7-11). 

The imidazole, benzoxazole, and benzthiazole derivatives in Table 7-3 are rather moisture-sensitive.92 On the whole, however, the heteroarylstannanes show the same reactions that characterise the homoarylstannanes. With a palladium catalyst, they undergo coupling112 and cross-coupling reactions68 and indeed much of the recent interest in the heteroarylstannanes stems from their applications in the Stille reaction (see Section 22.2). One aspect of this is the synthesis of oligomers and polymers or copolymers, for example by the cross-coupling of 2,5-distannylthiophene with a 1,4-diiodo-arene.113,114... 

In this chapter we focus on applications of the Stille coupling reaction for the synthesis of complex natural products published in recent years (mainly the last 10 years). The chapter is organized by the type of bond being formed in the cross-coupling reaction. 

Several new alternatives to the classical methods of synthesis of biheterocycles have been developed. Most notable among these are low-valent transition metal-catalyzed homo-coupling reactions, which are particularly applicable to the synthesis of biheterocycles, and which give much better yields than the earlier Ullmann and Busch procedures. Furthermore, un-symmetrical biheterocycles are now more readily available by way of palladium-catalyzed cross-coupling reactions, such as the Stille and the Suzuki procedures. Thus, many new members of the biheterocyclic series are now available for study. As a consequence of the increased sophistication of molecular structure determination techniques, aromatic biheterocycles have been the subject of many recent spectroscopic and X-ray crystallographic studies, as well as numerous molecular orbital and molecular mechanics calculations. 

In 2003, when the second edition appeared, it was clear that the Stille chemistr/ had really come of age, as shown by the increasing number of applications of palladium-catalyzed cross-coupling reactions of vinyl- and arylstannanes in natural product synthesis and in advanced organic synthesis. In the past decade, these types of applications, of course, remained very important and, in addition, the use of allylstannanes in palladium-catalyzed coupling reactions received much attention. Cross-coupling of allylstannanes with imines also forwarded the area of asymmetric catalysis. 

Nucleophilic attack on Pd-bound ligands, be they a, tt, or (t-tt, provides an assortment of excellent methods for the formation of carbon-carbon and carbon-heteroatom bonds, as represented by general transformations shown in Scheme 1. In particular, these processes have provided three major methods for the formation of the carbon-heteroatom bonds, and they have extensively been applied to the synthesis of natural products. More recently, the Pd-catalyzed cross-coupling has also been developed so as to be applicable to the formation of C— N, C—O, and other carbon-heteroatom bonds, as discussed in Sect. III.3, even though the current scope of their application to natural product synthesis is still rather limited. 

---