Intramolecular Stille Cross-coupling

Since the first intramolecular version described by Pierce in 1985 [111], the Stille cross-coupling has proven to be an ideal reaction to get rings ranging from four to 

Aryl-aryl cyclizations were used for the preparation of polyaromatic compounds, cryptands and heterocydes. A particularly interesting version is the Still-Kelly cyclization that was used for the synthesis of phenanthro [9,10-d]pyrazoles involving the intermolecular formation of the aromatic stannane followed by an intramolecular coupling with the aryl halide moiety [128]. Benzo [4,5]furopyri-dines [129] and dibenz [c,a]azepines [130] were prepared by related intramolecular coupling of diodides in the presence of hexamethylditin. 

---

Thus, an efficient and convergent total synthesis of ( )-isocembrene has been accomplished in seven steps from the known geranylacetone through an intramolecular Stille cross-coupling reaction. The strategy is of great potential for the divergent synthesis of complex cembrane-type diterpenoids such as cembrene-C and sarcophytols. 

An analogous 5-exo-dig carbopalladation, performed on an iodoarene with an ortho-alkynylamino substituent in the presence of hexabutyldistannane, produces an alkenyl-stannane, which undergoes a second cyclization by intramolecular Stille cross-coupling with the second o-iodoaniline moiety in the molecule. The hnal product, though, arises by double bond migration (Scheme 25, Eq. 1). Alternatively, a 1,1-disubstituted aUcene... 

Z-tamoxifen 403 tandem cyclization 290, 295 tandem Heck reaction-anion capture 253-4 tandem Heck reaction-phenoxide capture 253 tandem Heck reactions 251, 252-4 tandem intramolecular Heck-intermolecular Stille cross-coupling 255 taxol 140, 143,243,245 ( )-tazettine 146,234 telomerization 352 telomerization products 343, 345 template effect 140 teraconic anhydride 468 terminal acetylenes, synthesis of 216-20 terminal alkynes 6, 213 terminal 2,2-diorgano-l-aIkcnylboronates 51 terminal diynes 207 ternary complex 444 ternary coupling 177... 

Scheme 6-28 Tandem intramolecular Heck-intermolecular Stille cross couplings.

Readily available functionalized aryl siloxanes are also viable cross-coupling partners for Pd(dba)2-catalyzed allylic arylations. A mixture of 5% Pd(dba)2, allylic halide, and in situ-generated aryl zinc reagent produces allylated arenes in high yield. Aryl boronic acids have been converted to allylated arenes as well. Diastereoselective intramolecular Stille-type coupling of two allylic moieties (aUylic acetate and allylic stannane) has been performed in high yield to produce the key intermediate in the synthesis of racemic 10-ep/-elemol (eq 19). ... 

An intramolecular palladium(o)-catalyzed cross-coupling of an aryl iodide with a trans vinylstannane is the penultimate maneuver in the Stille-Hegedus total synthesis of (S)-zearalenone (142) (see Scheme 38).59 In the event, exposure of compound 140 to Pd(PPh3)4 catalyst on a 20% cross-linked polystyrene support in refluxing toluene brings about the desired macrocyclization, affording the 14-membered macrolide 141 in 54% yield. Acid-induced hydrolysis of the two methoxyethoxymethyl (MEM) ethers completes the total synthesis of 142. 

In the presence of in, V -generated palladium(O) species, an electrophilic 7t-allyl complex 228 is formed, which is readily engaged in an intramolecular carbometallation (Scheme 57). The resulting vinylpalladium species then undergoes a Stille-type cross-coupling to provide a triene.232... 

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... 

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. 

Good yields are achieved for five- and six-membered ring cyclizations by the intramolecular cross-coupling reaction of haloalkenes [139, 152], but the scope of reaction is still limited by the availability of the haloalkenes, particularly because of the absence of a simple method for preparing cyclic haloalkenes from ketone precursors. The ready availability of triflates from carbonyl compounds now offers a valuable tool for the annulation of ketones (Scheme 2-56) [160]. 

Caldirola, P., Chowdhury, R., Johansson, A. M., Hacksell, U. Intramolecular Transfer of CO from (q6-arene)Cr(CO)3 Complexes in Stille-Type Palladium-Catalyzed Cross-Coupling Reactions. Organometallics 1995,14, 3897-3900. 

Imine formation. An example of this route is Echavarren and Stille s use of a simple intramolecular imine formation between a quinone moiety and an amino group to complete the nucleus (Scheme 25) of amphi-medine 105 (88JA4051). The quinone 159 was prepared by a palladium-catalyzed cross-coupling of 5,8-dimethoxyquinolin-4-yl triflate 157 (from... 

---