Stille coupling synthetic utility

Hartwig-Buchwald, Suzuki, and Stille type cross-coupling reactions with key intermediate 46 led to a wide range of substituted sulfoximines such as 47-49 [37]. In order to demonstrate the synthetic utility of the resulting products, pseudo tripeptide 50 was prepared from a related intermediate. 

Milstein, D., Stille, J. K. Palladium-catalyzed coupling of tetraorganotin compounds with aryl and benzyl halides. Synthetic utility and... 

Functionalized alkenyl diamino- and dialkoxyboranes have been produced regio-and stereoselectively through addition of carbon- or heteroatomgenerated from bromotrichloromethane, thiols, phosphines and tributyltin hydride) to ethynylbis(diisopropylamino)boranes. The synthetic utility of these reactions was illustrated by the preparation of stereodefmed (Z)- or ( )-alkenylboronic esters via palladium-catalyzed crossStille reaction and a Suzuki coupling under basic conditions can be further conducted (Scheme 9.14) [33]. 

The [2,3]-Stevens rearrangement is a thermal sigmatropic rearrangement of an ammonium ylide (38) to form unnatural amino acid derivatives 39 (Scheme 12). Traditionally, the ammonium ylides have been formed through alkylation of aminoesters 36 with aUcyl halides 37 to form quaternary salts followed by treatment with base. Although effective, the harsh conditions lead to side products and limited substrate scope. More recently, the coupling of diazoesters 40 and allylic amines 41 in the presence of metals like copper, rhodium, and palladium has been developed for the direct constmction of ammonium ylides 38 via metal carbenoid intermediates. " Although this approach represented an advance over the traditional alkylation chemistry, the use of diazoesters still limits the synthetic utility of these reactions. 

Carreira and co-workers have also extended the scope of aldehydes that may be utilized in catalytic addition reactions to include stannylpropenal 108 as a substrate (Table 8B2.12, Entry 7). The adduct produced from the aldol addition of 105 is isolated with 92% ee and serves as a useful building block, as it is amenable for further synthetic elaboration (Scheme 8B2.9). Thus, vinylstannane 109 is a substrate for Stille cross-coupling reactions to give a diverse family of protected acetoacetate adducts 110. Following deprotection of the masked keto ester, the corresponding hydroxy keto ester 111 may be converted to either the syn or anti skipped polyols 112 or 113. A recent total synthesis of macrolactin A by Carreira and co-workers utilizes aldol... 

Workers at Sphinx [24] have published a synthetic route to a series ofhighly functionalized biphenyl compounds. The key reactions in this sequence are the biaiyl Stille and/or Suzuki couplings to form the biphenyl nucleus and the use of Mitsunobu chemistry to attach the variable side chains (Fig. 2). The illustrated route utilizes a solution-based diaryl coupling followed by on-resin Mitsunobu reactions. Although the diaiyl coupling proceeds on solid phase, this group s desire to maximize resin loading prompted them to implement the former route. 

The examples discussed in this paper demonstrate that Pd-catalyzed coupling reactions can be successfully utilized in the convergent (modular) synthesis of vitamin D-active compounds. The new synthetic routes open an efficient and highly selective access to a variety of vitamin D analogs. While reliable methods exist today for the construction of the triene system and for the synthesis of the ring A precursors, the search for efficient total synthetic approaches to the CD building blocks still remain a challenging task for the future. 

The use of aryl triflates or other sulfonates in the amine arylation reaction is highly desirable from a synthetic standpoint since a large variety of phenols are easily accessed and derivatized. Aryl and vinyl triflates have enjoyed great utility in other Pd-catalyzed transformations such as the Stille [77] and Suzuki [78] couplings, and the Heck [79] reaction. 

Spiro-linked compounds containing heterocyclic units have been prepared for many apphcations. In general, there are two synthetic pathways to build up heterocyclic spiro compounds. On the one hand, cross-coupling reactions like the Negishi, Kharash, Stille, Suzuki, or Sonogashira coupling reaction can be utilized to connect the heterocychc subunit with the central spiro core [118]. On the other hand, the heterocycle can be built up from spiro precursors containing heteroatoms. 

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