Coupling precursor stannanes

The heteroaromatic stannanes undergo the normal electrophilic substitution reactions of their protic precursors, and often to an enhanced degree. They are often prepared with the aim of a subsequent Stille cross-coupling reaction, and oligothiophenes with potentially useful optical and electron properties have been prepared by coupling between stannyl- and bromo-thiophenes, for example, Equation (63).204... 

A Stille type coupling strategy has been utilised to complete a total synthesis of epothilone E. The vinyl iodide 30 and the thiazole stannane 31 were coupled to give the macrolactone 32 which is a precursor to natural epithilone E. The thiazole stannane 31 was prepared from 4-bromo-2-hydroxymethylthiazole via treatment of the lithiated protected 4-bromO 2-hydroxymethylthiazole with tributylstannyl chloride. This Stille coupling approach was also used to prepare a range of epothilone B analogues <99BMC665>,... 

Substitution at the terminal position of the allylstannane, as in crotonyltributyl stannane, however, is not tolerated, because hydrogen abstraction from the allylic position is a competing reaction [21], An extension of the method involves the coupling of the anomeric radical precursors 28 with the allyltributyltin reagent 29 [14], In the reagent 29 the double bond is activated toward addition of nucleophilic radicals by the electron-withdrawing t-butoxy carbonyl group. The obtained product 30 has been useful en route to 3-deoxy-D-marmo-2-octulosonic acid (KDO). 

The Stille coupling of a-bromoenone 83 with the previously known [30] stannane 93 proceeded uneventfully and gave amidotriene 82, the key precursor for the planned electrocyclization reaction. Heating 82 in refluxing... 

Another principal method is the fluorovinylation of suitable precursors by transition metal-catalyzed carbon-carbon coupling reactions [13]. Activated fluorovinyl species can be conveniently generated in situ from commonly used hydrofluorocarbons, for example HFC-134a [14] (Scheme 2.192). Fluorinated vinyl zinc halides are often used for the coupling reactions, but other activated species, for example stannanes [15] or boronates [16], have also been applied successfully. 

The oxidative palladium 1 1-insertion complex intermediates (300) and (301) in the coupling reaction between 2,4-dichloropyrimidine, or 5-bromo-2-methanesulfonylpyrimidine, and tetra-kis(triphenylphosphine)- or tetrakis(triisopropyl phosphite)-palladium can be isolated and purified by conventional methods (Scheme 49). The regioselectivity of the insertion reaction in 2,4-dichloropyrimidine is in accord with the 4-regiochemistry in coupling reactions (Section 6.02.5.5.4). The palladized pyrimidines react readily with organnostannnanes, and may serve as catalysts in coupling reactions between the respective pyrimidine precursor and stannanes <90ACS927>. 

Indeed, stannanes have largely dominated the class of reagents used to effect hydrogen transfer because of favorable rate constants (A h) for the hydrogen transfer step itself [27] coupled with excellent rate constants for subsequent reaction with a wide cross-section of radical precursor (A x) [1] the prototypical chain process is illustrated in Scheme 12. 

The completion of the steroid skeleton proceeded as follows. After Stille coupling of the vinyl stannanes 45 with the more reactive triflate 46, the resulting vinyl bromide product 47 was converted into the Diels-Alder precursor 48 via a Heck reaction. A quick Diels-Alder reaction gave steroid intermediate 49. Significant alterations of this analog and other steroid skeleta were carried out to produce novel steroids for biological testing. 

Like members of the endiandric acid family, ocellapyrone A (5) has a bicyclo[4.2.0]octadiene framework. As such it was hypothesised that 5 is also biosynthesised from a tetraene precursor via an 8k-6k electrocyclisation cascade. To test this hypothesis, Trauner et al. constructed the pyrone-polyene 35 using a StiUe coupling of the pyrone fragment 34 with the stannane 33 [14], The tetraene 35 underwent an 8k-6k electrocyclisation cascade in situ. The product of the initial 8k cychsation, 36, exists as a mixture of exo and endo conformers, with subsequent 6k cychsation of these conformers leading to oceUapyrone A (5) and isomer 37 respectively. The endo product 37 was found to dominate. OceUapyrone B (6) was obtained by exposure of 37 to oxygen (Scheme 1.6). 

A closely related approach has been described using tributyl(3,3,3-trifluoro-l-propynyl)stannane as a dipolarophile [135]. Once again, stanylated triazoles are useful precursors for coupling reactions [136] (Scheme 53)... 

---