Stille reaction intramolecular

Intramolecular Pd(0)-catalyzed Stille reaction of organotin reagents with electrophiles leading to C—C a-bond formation in synthesis of heterocycles, particularly, macrocyclic lactones 99JCS(P1)1235. 

Scheme 36. Piers s annulation strategy based on the intramolecular Stille reaction.

Compared to the previously described transition metal-catalyzed transformations in this chapter, microwave-assisted Stille reactions [74] involving organotin reagents as coupling partners are comparatively rare. A few examples describing both inter- and intramolecular Stille reactions in heterocyclic systems are summarized in Scheme 6.38 [47, 75-77]. Additional examples involving fluorous Stille reactions are described in Section 7.3. 

Scheme 3 Macrocylization by intramolecular Stille reaction to protected macrolactin A by Pattenden...

An example is the intramolecular Stille reaction described by Pattenden in his synthetic studies towards macrolactin A (19, Scheme 3) [51]. 

Quayle, P. Wang, J. Xu, J. Urch, C. J. On the cine substitution of l,l-bis(tributylstanny-ljethenes in an intramolecular Stille reaction. Tetrahedron Lett. 1998, 39, 489H-92. 

Stannaries have become prominent in multifunctional anchoring groups. A polymer-bound tin hydride 41 has been used to hydrostannylate alkynes under the action of palladium-catalysis to give polymer-bound alkenylstannanes 42. These alkenyl stannanes have been employed in intermolecular [45] and intramolecular Stille reactions [46]. Alkenylstannanes can also undergo protonation to give alkenes 44 in a traceless fashion. This linker is therefore multifunctional (Scheme 6.1.12). 

With respect to this, Ellman and coworkers [16], Zhu and coworkers [17], Amusch and Pieters [18], and Liskamp and coworkers [19] have prepared (monocyclic) mimics of the D-E part of the cavity of these antibiotics via an intramolecular nucleophilic aromatic substitution [16-18] or a Sonogashira-based macrocyclization [19] (Figure 1.4). Recently, a bicydic mimic of the C-D-E cavity, which was prepared by a Stille reaction followed by tandem ring-dosing metathesis (9, Figure 1.4), was described by liskamp and coworkers [20]. Considerable challenges lie ahead for the synthetic chemist in order to develop practical syntheses of mimics of vancomydn capable of binding not only D-Ala-D-Ala, but also cell wall parts of resistant bacteria, i.e. D-Ala-D-lactate. 

The Stille reaction, which represents over half of all current cross-coupling reactioi has been used in total synthesis with excellent results. The reaction may also be carried o intramolecularly and with alkynyl stannanes instead of the more usual aryl or vinyl stannan even to form medium-sized rings. This example forms a ten-membered ring containing t alkynes. 

Pattenden, G., Sinclair, D. J. The intramolecular Stille reaction in some target natural product syntheses. J. Organomet. Chem. 2002, 653, 261-268. 

Scheme 5.4.21 Intramolecular macrocycllzatlon by using the Stille reaction In the synthesis of the thiazolyl peptide CE2270 A (TBDMS tert-butyidimethylsllyl)...

The versatility of the Stille reaction was illustrated in the preparation of all four benzo[4,5]furopyridines [98]. Inter- and intramolecular variations of the reaction were exploited in this work. The alkoxide of 273 underwent a displacement reaction of chloride of 272 to generate 274. Ring closure to afford 275 was accomplished using the Kelly-variation of the Stille reaction. 

In their synthetic studies towards lophotoxin and pukalide, Paterson and coworkers explored both intermolecular and intramolecular Stille coupling reactions [108]. The intermolecular approach between vinyl iodide 107 and furylstannane 108 is more successful, giving adduct 109 in 67% yield. The intramolecular version provides the macro-cyclized 14-membered lactone in only 15% yield. Pattenden reported a related investigation towards the synthesis of lophotoxin and observed comparable inter- and intramolecular reactivity in similar Stille reactions [109]. 

Scheme 17. An intramolecular aryl dihalide tandem cyclization via the Stille reaction...

Mitchell et al. utilized an intramolecular Stille reaction for the total synthesis of rhizoxin D.229 The... 

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