Palladium-catalyzed reactions alkyne reduction

Disubstituted silole derivatives are synthesized by the palladium-catalyzed reaction of (trialkylstannyl)di-methylsilane with terminal alkynes (Equation (107)).266 The mechanism is supposed to involve a palladium silylene complex, which is generated via /3-hydride elimination from LJ3d(SiMe2H)(SnBu3) (Scheme 62). Successive incorporation of two alkyne molecules into the complex followed by reductive elimination gives rise to the silole products. 

Preparation of the lactone fragment started with a mixture of (2 ,45) and (25,4S)-4-methyl-2-phenylsulfenyl-y-butyrolactone (53) which was alkylated with ( )-l,9-diiodo-l-nonene. The corresponding iodo compound 100 so obtained was then coupled with the alkyne 99 through the efficient palladium catalyzed reaction (Pd(PPh3)4, Cul, Et3N, room temperature) in 86 % yield. Enyne reduction of 101 with Wilkinson s catalyst, then oxidation of the sulfide into sulfoxide and subsequent thermal elimination gave rise to the title compound 90. The synthesis was achieved in 20 steps and in 0.36 % yield. 

Complexes of internal alkynes of general formula Pd(7] -alkyne)(PR3)2 or Pd( 7 -alkyne)(diphos) have been reported, often prepared in the course of palladium-catalyzed reactions and other processes. Thus, most of them have been synthesized by decomposition of Pd(ii) complexes in the presence of the alkyne as shown in Equations (20) and (21). Insertion into a Pd-E bond and reductive elimination generates the silylated or stannylated alkene and Pd(0), which is trapped by the alkyne in excess. 

This reaction typifies the two possibilities of reaction routes for M-catalyzed addition of an S-X (or Se-X) bond to alkyne (a) oxidative addition of the S-X bond to M(0) to form 94, (b) insertion of alkyne into either the M-S or M-X bond to provide 95 or 96 (c) C-X or C-S bond-forming reductive elimination to give 97 (Scheme 7-21). Comparable reaction sequences are also discussed when the Chalk-Harrod mechanism is compared with the modified Chalk-Harrod mechanism in hydrosily-lations [1,3]. The palladium-catalyzed thioboratiori, that is, addition of an S-B bond to an alkyne was reported by Miyaura and Suzuki et al. to furnish the cis-adducts 98 with the sulfur bound to the internal carbon and the boron center to the terminal carbon (Eq. 7.61) [62]. 

In the early 1980s, one of the first preparations of substituted allenes was reported, which employed a palladium-catalyzed cross-coupling reaction of allenyl halides [9]. In this study, allenyl bromides 13 and various Grignard reagents 14 were coupled in the presence of catalytic amounts of a Pd(0) species, generated in situ by reduction of a Pd(II) salt. Trisubstituted allenes 15 were obtained with high regioselectivity (allene 15 alkyne 16 = 90 10 to 99 1) (Scheme 14.5). 

Particularly interesting is the reaction of enynes with catalytic amounts of carbene complexes (Figure 3.50). If the chain-length between olefin and alkyne enables the formation of a five-membered or larger ring, then RCM can lead to the formation of vinyl-substituted cycloalkenes [866] or heterocycles. Examples of such reactions are given in Tables 3.18-3.20. It should, though, be taken into account that this reaction can also proceed by non-carbene-mediated pathways. Also Fischer-type carbene complexes and other complexes [867] can catalyze enyne cyclizations [267]. Trost [868] proposed that palladium-catalyzed enyne cyclizations proceed via metallacyclopentenes, which upon reductive elimination yield an intermediate cyclobutene. Also a Lewis acid-catalyzed, intramolecular [2 + 2] cycloaddition of, e.g., acceptor-substituted alkynes to an alkene to yield a cyclobutene can be considered as a possible mechanism of enyne cyclization. 

The insertion of CO into palladium carbon bonds is a common step in many palladium-catalyzed carbonylation reactions and polymerizations. This reaction takes place under moderate CO pressure (1-3 atm). From the range of compounds that can be carbonylated, it can be inferred that CO will insert into alkyl, aryl, and alkynic bonds (equation 13). One of the few types of Pd-C bonds inert to CO insertion is the Pd-acyl bond, thus only single carbonylations are normally observed. However, a few examples of double carbonylation have been reported. In the case of palladium-catalyzed formation of PhCOCONEt2 from Phi, CO, and NHEt2, reductive elimination from a bisacyl complex has been established as the mechanism, rather than CO insertion into a Pd-acyl bond. 

In six more steps alkyne 22 is transformed into sulfone 24 (building block III) for the final coupling reaction. These steps include TBS deprotection (75 %, over 2 steps from 20), palladium-catalyzed addition to methoxy tetrolate (61 %), DIBAL reduction (91 %), Mukaiyama redox condensation (86 %), acetylation (97 %) and (NH4)6Mo7024-catalyzed oxidation with H2O2 (99 %). 

The palladium-catalyzed reductive enyne cyclization reaction occurs with cis addition at the alkyne moiety and is highly diastereoselective with respect to the newly formed stereogenic centers21. This is demonstrated with various substituted enynes, leading to single diastereomer-ic cyclization products21. 

Internal alkynes will also readily undergo palladium-catalyzed annulation by functionally substituted aromatic or vinylic halides to afford a wide range of heterocycles and carbocycles. However, the mechanism here appears to be quite different from the mechanism for the annulation of terminal alkynes. In this case, it appears that the reaction usually involves (1) oxidative addition of the organic halide to Pd(0) to produce an organopalladium(II) intermediate, (2) subsequent insertion of the alkyne to produce a vinylic palladium intermediate, (3) cyclization to afford a palladacycle, and (4) reductive elimination to produce the cyclic product and regenerate the Pd(0) catalyst (Eq. 28). 

Palladium-catalyzed hydrostannation of alkynes proceeds regio- and stereospecifically to afford the synthetically useful ( )-vinylstannanes. This reaction implies oxidative addition of RsSn—H to Pd(0) to generate a Pd(ll) hydrido stannyl intermediate, which then undergoes cis addition of the Pd—Sn bond to the alkyne bond, followed by reductive elimination of the ( )-vinylstannane. The supposed cis-PdCII) hydrido trialkylstannyl intermediates had so far remained elusive. Very recently, cis-PdCll) hydrido trialkylstannyl complexes have been synthesized for the first time. ... 

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