Stille coupling 2- allyl acetate

The Stille reaction has been successfully applied to a number of macrocyclic ring closures.207 In a synthesis of amphidinolide A, the two major fragments were coupled via a selective Stille reaction, presumably governed by steric factors. After deprotection the ring was closed by coupling the second vinyl stannane group with an allylic acetate.208... 

Murakami generated 3-tributylstannylindoles in situ (but also isolable) using 3-bromoindole 174, allylic acetates and carbonates, and hexamethylditin [179]. A typical procedure is illustrated for the synthesis of 175. The corresponding 5-bromo analog is allylated to the extent of 59%. 3-Stannylindoles couple smoothly in tandem fashion with 2,3-dibromo-5,6-dimethylbenzoquinone under Stille conditions [180]. 

Scheme 16.11 shows the completion of the total synthesis of azaspiracid-1, which followed with slight modifications, the synthesis of the originally proposed structure of azaspiracid-1 (la). This chemistry was also carried out with the corresponding ABCD enantiomer in similar yields. Thns, lithiation of dithiane 51 (n-BuLi n-BnjMg) followed by addition into pentafluorophenol ester 68 resulted in CJ-C27 ketone 69 (50% yield). Ketone 69 was then elaborated into diacetate 70, this time as the TBS ether at C-25, as this protecting group was easier to remove than the acetate used in the earlier work directed toward the original stractnre (see Scheme 16.8). Stille coupling of this allylic acetate (70) then proceeded smoothly, as before, affording the complete Cj-C q backbone 71, which was successfully elaborated to the correct structure of azaspiracid-1 (1), identical in all measured physical properties ( H NMR, C NMR, Rf, [aj ) to the natural material.

Compared with the previous coupling types, much less has been reported with these relatively more difficnlt conplings. Exceptionally, conplings with allyl electrophiles, usually allyl acetates or halides, have been often nsed in the synthesis of complex natural products.A noteworthy example is the synthesis of the azaspiracids 1-3 (115a-c), neurotoxins isolated from mussels, whose structure was determined by total synthesis by Nicolaon and coworkers.This synthesis features a notable Stille... 

The alkenylpalladium species resulting from electrophilic attack of a 7r-allylpalladium species, generated from an allyl acetate on a tethered alkynyl group, can also undergo an intramolecular Stille coupling with tributylallylstannane (Scheme 27). 

One distinguishes palladium(0)- and palladium(ll)-catalysed reactions. The most common palladium(O) transformations are the Mizoroki-Heck and the cross-coupling transformations such as the Suzuki-Miyaura, the Stille and the Sonogashira reactions, which allow the arylation or alkenylation of C=C double bonds, boronic acid derivates, stan-nanes and alkynes respectively [2]. Another important palladium(O) transformation is the nucleophilic substitution of usually allylic acetates or carbonates known as the Tsuji-Trost reaction [3]. The most versatile palladium(ll)-catalysed transformation is the Wacker oxidation, which is industrially used for the synthesis of acetaldehyde from ethylene [4]. It should be noted that many of these palladium-catalysed transformations can also be performed in an enantioselective way [5]. 

The research groups of Trost and Stille have demonstrated in related studies that allylic stannanes undergo palladium-catalysed cross-coupling with allylic acetates °° or allylic bromides to furnish 1,5-dienes in variable yields. The stannane undergoes predominant or complete allylic transposition during coupling with either type of substrate (e.g. Scheme 96). 

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 (allylic acetate and allylic stannane) has been performed in high yield to produce the key intermediate in the synthesis of racemic 10-e/Ji-elemol (eq 19). ... 

In conjunction with soft ligands such as AsPhs, the copper salt can accelerate the rate of cross coupling drastically in conventional Stille coupling protocol. These improved coupling conditions have been applied to the total s)Tithesis of guanacastepenes A, E, and of (—)-Gambierol, wherein the coupling of a (Z)-vinyl bromide or allyl acetate with a vinyl stannane or silane was achieved in excellent yield (eqs 22 and 23). 

A very comprehensive and critical review on the Stille reaction covering the literature up to 1995 appeared recently [94 a]. Although the Stille reaction can take place in the presence of many useful functional groups (e.g. alcohol, ester, nitro, acetal, ketone, and aldehyde [94,124 b]), it does not seem to be favored over the Suzuki or Kumada coupling for formation of biaryls, presumably because of the lower yields sometimes obtained in the Stille procedure [124]. In general, the Stille procedure is far more often applied for the introduction of other unsaturated groups (e.g. ethenyl, allyl, alkynyl) into aromatic systems than for aryl and... 

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