Pd -catalyzed cross-coupling with

The cis thioboration of terminal alkynes with 9-(arylthio)-9-BBN is catalyzed by Pd(Pli3P)4 in the presence of styrene. The product 136 is converted into the vinyl sulfides 137 and 138 by the treatment with MeOH or by Pd-catalyzed cross-coupling with aryl or alkenyl halides using K3PO4 in DMF[68]. No thioboration takes place with internal alkynes. 

Radical-mediated silyldesulfonylation of various vinyl and (a-fluoro)vinyl sulfones 21 with (TMSlsSiH (Reaction 25) provide access to vinyl and (a-fluoro)vinyl silanes 22. These reactions presumably occur via a radical addition of (TMSlsSi radical followed by /)-scission with the ejection of PhS02 radical. Hydrogen abstraction from (TMSlsSiH by PhS02 radical completes the cycle of these chain reactions. Such silyldesulfonylation provides a flexible alternative to the hydrosilylation of alkynes with (TMSlsSiH (see below). On oxidative treatment with hydrogen peroxide in basic aqueous solution, compound 22 undergoes Pd-catalyzed cross-couplings with aryl halides. 

Other tin reagents have found use in Pd-catalyzed cross-couplings with halopyridines as well. The Stille coupling of 3-iodopyridine with ethoxy(tributylstannyl)acetylene gave rise to 3-ethoxyethynylpyridine (100), which was then hydrolyzed to the corresponding ethyl 3-pyridylacetate (101) [88], Carbamoylstannane 102 was prepared by sequential treatment of lithiated piperidine with carbon monoxide and trimethyltin chloride. Stille coupling of carbamoylstannane 102 and 3-bromopyridine provided a unique entry to amide 103 [89],... 

The related cyclization of 2-ethynylanilines 67 also represents one of the usefiil methods for the synthesis of 2-substituted indoles since the precursors are easily prepared from 2-haloanilines 66 by Pd-catalyzed cross-coupling with terminal alkynes. Althou cyclizations of such alkynes are normally effected using Cu(I) or Pd(II) species, Sakamoto showed that in the absence of such metals, base catalysis (e.g., NaOEt) alone can accomplish the same goal. This author now reports that tetrabutylammonium fluoride (TBAF) is capable of inducing cyclization to the indoles 68 without affecting functionalities such as bromo, cyano, ethoxycarbonyl, and ethynyl <99JCS(P1)529>. 

SCHEME 25. High turnover numbers observed in the Pd-catalyzed cross-coupling with Pd(dppf)a2 or Pd(DPEphos)Cl2 as a catalyst... 

With the aid of a fluoride ion source, alkynyltrimethylsilanes work as effective alkynyl donors in the Pd-catalyzed cross-coupling with alkenyl iodides.43,43a Recent studies have revealed that the alkynylsilanes react smoothly with aryl iodides and triflates, alkenyl triflates, or alkynyl chlorides under co-catalysis by a Cu or Ag salt.45 46a The use of a Pd/imidazolium chloride system in the presence of Cs2CC>3 and a Cu co-catalyst enables an efficient coupling between alkynyltrimethylsilanes and aryl bromides.47 In some cases, this catalytic system works well under Cu-free conditions. Alkynylsilanols also can be used as alkynyl donors in the coupling with aryl iodides.48 49 When TBAF is employed as activator, the coupling proceeds efficiently without co-catalyst.48... 

Acylsilanes serve as acyl donors in the Pd-catalyzed cross-couplings with allyl trifluoroacetates,243 aryl halides,244 and alkenyl halides.2 Intramolecular acylation of alkynes with acylsilanes proceeds under catalysis by [RhCl(CO)2]2.246... 

Pd-catalyzed cross-coupling with ethynylstannane is a useful procedure for the introduction of tlie ethynyl group into the cyclopentadienyl ligand of organometallic complexes. Thus, the reaction of the iodocyclopentadienyl complex 125 with ethynylstannane affords the ethynylated product 126 under mild conditions in the presence of PdCl2(CH3CN)2 in 86% yield [Eq. (41)] [62]. 

Researchers at Pfizer were interested in preparing 3-aryl azetidines in efforts to identify new drug candidates for the treatment of asthma. A general approach was developed in which the organozinc species of the azetidine 29 was prepared via Zn insertion into the C-I bond followed by Pd-catalyzed cross-coupling with aryl halides. Using this process, 5-bromopyridine was coupled to produce 31 in 46% yield [17]. 

Thioesters are readily accessible and have recently been shown to undergo Pd-catalyzed cross coupling with boronic acids to prepare ketone products. This chemistry has expanded to Stille cross coupling. The key to the reaction is the addition of stoichiometric amounts of Cu -diphenylphosphinate [60]. Stille coupling of thioester 142 with 2-tributylstannylpyrimidine affords the desired product 143 in 61% isolate yield. 

Asymmetric hydrogenation of bromo-substituted aromatic a-enamides 14 affords the corresponding bromo-amino acid derivatives 15, which subsequently is subjected to Pd-catalyzed cross-coupling with aryl and vinyl boronic acids. In addition to diverse phenylalanine derivatives 16, a broad array of other novel aromatic and heterocyclic amino acids have been produced rapidly from a small number of bromo-functionalized intermediates [24], This same two-step process may be applied to the production of many other classes of aromatic and heterocyclic chiral building blocks, such as arylalkylamines, amino alcohols, diamines, and directly on peptides as well. 

Several N-protected indol-2-yltributylstannanes were examined in Pd-catalyzed cross-coupling with aryl halides and triflates, acyl chlorides and benzylic and allylic bromides. <94J0C4250> The 1-methyl and l-(2-trimethylsilylethoxymethyl) (SEM) derivatives reacted readily whereas the 1-t-butoxycarbonyl derivative was somewhat less reactive. The SEM group is removable with BU4N F , providing acces to the deprotected 2-substituted indoles. 

Allylic compounds undergo smooth Pd-catalyzed cross-coupling with main group organometallic compounds as expected. Substitution occurs mainly at less-substituted allylic termini. A few examples are cited here. 

The Pd-catalyzed cross-coupling with alkynylzincs appears to be considerably more general than the Sonogashira alkynylation. However, the operational simplicity may favor the latter in most of those cases where both are comparably satisfactory. On the other hand, there have been an increasing number of cases where the alkynylzinc reaction is decidedly more favorable than the Sonogashira reaction. 

Alkenylsilicon compounds themselves are generally inert in Pd-catalyzed cross-coupling with aryl electrophiles. However, their reactivity could be remarkably enhanced by the addition of fluorides to generate pentacoordinate alkenylsilicon derivatives that can undergo the desired cross-coupling. Some typical examples are shown in... 

The use of di-a, 8-substituted alkenylalkoxysilanes in Pd-catalyzed cross-coupling with aryl halides has been demonstrated. i -phe synthetic utility of these coupling reactions has further been demonstrated by the one-pot transformation of a homopropargyl alcohol to regio-and stereodeflned trisubstituted homoallyl alcohol (Protocol 1), as shown in Scheme 32. 

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