The Intramolecular Stille Reaction

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

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

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

Another palladium-catalysed process that has proven utility for cyclic structures is the Stille coupling between organostannanes and aiyl or vinyl halides/triflates. Specifically for the macrocyclic framework, this chemistry was applied to the preparation of cyclic trienes (102) with defined geometry (Scheme 11.11) that were intermediates for transannular Diels-Alder reactions. The intramolecular Stille reaction also has been efficiently conducted on solid phase to form 104, an advanced intermediate in the synthesis of (S)-zearalenone, from 103 by a cyclization-release strategy. ... 

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. 

Wong reported that stoichiometric amounts of copper(I) chloride alone can promote the intramolecular Stille coupling (equation 138)243. In fact, copper(I)-mediated reaction was cleaner and faster compared with that catalysed by Pd(0) species. Selected examples of intermolecular Stille coupling reactions leading to dienes (Table 25)236a,242b 244, polyenes (Table 26)245 and macrocyclizations (Table 27)246 are given in the respective tables. 

In Grigg s approach to hippadine (37), he established the connection between the two phenyl rings via the Stille-Kelly reaction [45]. When diiodide 35 was submitted to the Pd(0)/ditin catalyst system, the intramolecular cyclization was realized to establish the C—C bond in lactam 36. Oxidation of the indoline moiety in 36 using 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ) then delivered hippadine (37). Analogously, the intramolecular Stille coupling of dibromide 38 led directly to hippadine (37) [46]. 

While the perfluorinated acetates do prefer insertion, they are still capable of forming 1,3-dipoles and have demonstrated interesting effects on the regioselectivity of intramolecular cycloaddition reactions, presumably through Lewis acid-mediated effects on the dipolarophile [83]. Other chemoselectivity effects have been noted in the intramolecular cycloaddition reactions and may or may not be partially induced by conformation and sterics [84]. It was further demonstrated thaL when possible, O-H insertion is the predominant outcome over other types of insertion for rhodium]II)-car-benes, independently of the catalyst. However, cycloaddition reactions have been demonstrated to be hgand-dependent [85]. 

The formation of seven membered heterocycles and larger rings through cross-coupling reactions is quite rare (except for some macrocyclic natural products). An example of such a process is presented in 5.1. The intramolecular Stille-coupling of the tributylstannyl-indole and vinyl bromide moieties led to the formation of a seven membered ring in good yield.1... 

Boger and co-workers have studied the intramolecular Ullmann reaction extensively. Some representative examples are shown in Table 3. For substrates in which the N10 site is not methylated, the reaction is complicated by intramolecular N-acylation of the N10—Cu amide by the C12 carbamate. In some cases, the generation of this byproduct could be suppressed by using freshly dried and degassed solvent with purified CuBr-DMS complex. 10 However, in other cases, the byproduct was still produced and the yield of the desired product suffered accordingly. 27 ... 

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. 

The intramolecular Stille coupling of tributyl(3-(2-iodobenzyloxy)prop-l-en-2-yl)stannane 572 provides 4-methyl-eneisochroman 573 in good yield, with careful control of the reaction temperature necessary to prevent isomerization of the double bond to form 4-methylisochromene (Scheme 124) <2004JOC468>. 4-Methyleneisochroman 573 can also be synthesized via an indium-mediated intramolecular cyclization of 2-bromoallyloxymethyl iodobenzene 574 in excellent yield (Scheme 124) <20050L343>. 

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). 

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

C.ii.b. Stille Couplings. A polymer-bound tin hydride has been used to hydrostannylate alkynes under palladium catalysis hydrostaimylation to give polymer-bound alkenyl-stannanes.t Alternatively, the latter could be prepared from a polymer-bound tin chloride and an alkenyllithium or -magnesium halide reagent. These alkenylstannanes were employed in intermolecular as well intramolecular Stille reactions. The inter-molecular reactions provided the coupling products in good yields. In addition, the... 

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