Palladium-catalyzed cross-coupling reduction

The key step in a short and efficient synthesis of pleraplysillin-1 (127) is the palladium-catalyzed cross-coupling of vinylstannane 125 with vinyl triflate 126 (see Scheme 33). This synthesis is noteworthy in two respects. First, vinyl triflate 126 is generated regio-specifically from the kinetic enolate arising from a conjugate reduction of enone 124 the conjugate reduction of an enone is, in fact, a... 

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). 

The control of reactivity to achieve specific syntheses is one of the overarching goals of organic chemistry. In the decade since the publication of the third edition, major advances have been made in the development of efficient new methods, particularly catalytic processes, and in means for control of reaction stereochemistry. For example, the scope and efficiency of palladium- catalyzed cross coupling have been greatly improved by optimization of catalysts by ligand modification. Among the developments in stereocontrol are catalysts for enantioselective reduction of ketones, improved methods for control of the... 

Chloro-P-carboline (25) has served as a common intermediate in palladium-catalyzed cross-coupling reactions, offering easy access to several pyridine alkaloids. In Bracher s total synthesis of perlolyrine (27), a P-carboline alkaloid, the Suzuki reaction of 25 with 5-formylfuranyl-2-boronic acid (26) formed the C-C bond between the pyridine and the furan rings <92LA1315>. Reduction of the resulting Suzuki adduct with NaBIL subsequently... 

The reaction sequence starts by anchoring 2,6-dichloropurine onto the sohd-phase PAT, -amine at the more reactive C6 position with exclusive regioselectivity. A multitude of PAL-amine resins 59 can be prepared ahead by reductive amination of commercial (4-formyl-3,5-dimethoxyphe-noxy)-methylpolystyrene. The N9 position of the purine (60) may be modified by Mitsunobu alkylation. The final derivatization step involves a palladium-catalyzed cross-coupling reaction in position 2. This reaction... 

The palladium-catalyzed cross-coupling of an aryl, alkenyl, or benzylzinc bromide 11 with aryl iodide 12 succeeds with 0.15 mol-% [Pd P(C6H4C6Fi3)3 4] in toluene/1-bromoperfluorooctane, taking advantage of variable miscibility through thermoregulation [20], In this case the electron-deficiency of the phosphanes, due to the perfluorinated side chains, appears to influence the reductive elimination step in the cross-coupling reactions. 

Scheme 16 shows parallel syntheses of cyclic and acyclic amide compounds. Fluorous benzaldehydes were first subjected to reductive amination reactions. The resulting amines were then reacted with isocyanates to form substituted hydantoin rings 14 or with benzoyl chlorides to form amides 15. Purified F-sulfonates were used for palladium-catalyzed cross-coupling reactions to form corresponding biaryl 16 [31] and arylsulfide 17 [32] products, respectively. 

The mechanism of the Sonogashira reaction has not yet been established clearly. This statement, made in a 2004 publication by Amatore, Jutand and co-workers, certainly holds much truth [10], Nonetheless, the general outline of the mechanism is known, and involves a sequence of oxidative addition, transmetalation, and reductive elimination, which are common to palladium-catalyzed cross-coupling reactions [6b]. In-depth knowledge of the mechanism, however, is not yet available and, in particular, the precise role of the copper co-catalyst and the structure of the catalytically active species remain uncertain [11, 12], The mechanism displayed in Scheme 2 includes the catalytic cycle itself, the preactivation step and the copper mediated transfer of acetylide to the Pd complex and is based on proposals already made in the early publications of Sonogashira [6b]. 

Palladium and platinum form numerous alkyl complexes of the types M(R)(X)L2 and MR2L2, usually stabilized by phosphine ligands. The palladium compounds are prone to reductive elimination this is important in palladium catalyzed cross-coupling reactions (Section 21-14) ... 

The mechanism for this palladium-catalyzed cross-coupling reaction comprises the initial oxidative addition of the electrophile 37 to the palladium(O) catalyst followed by transmetallation of triethylsilane to yield the corresponding bis(organo)palladium(II) complex 39, which then undergoes reductive elimination to form the alkene 40 and to regenerate the palladium(O) catalyst. 

Reductive elimination of the unsymmetrical complexes is assumed to be the product-forming step in palladium-catalyzed cross-coupling reactions of organic halides... 

Few examples exist, but palladium-catalyzed cross-coupling of halogenoimidazoles with phenylsulfonylacetonitrile under basic conditions appears to provide examples of active methylene nucleophiles. As mentioned above (see Section 3.02.5.4.5), 5-iodo-l-methylimidazole is only reductively dehalogenated under the conditions, but 5-bromo-l-methyl-, 4-iodo-l-methyl-, and 2-bromo-l-methyl- (but not 2-chloro-l-methyl)imidazoles react successfully with the carbanion (Equation (31))... 

It was, however, impossible to obtain /V-alkyl or N-aryl substituted 1,3-benzaza-phospholes or pyrido-anellated 1,3-azaphospholes through the above route. However, palladium-catalyzed cross coupling, followed by reduction of the resulting o-ani-lino- or o-arninopyridophosphonates and condensation with dimethylformamide dimethylacetal led to the desired TV-substituted benzazaphospholes (36, X = CH) or pyrido-anellated azaphospholes (36, X = N) (Scheme 11) [43 47],... 

The generally accepted catalytic cycle for the Buchwald-Hartwig amination mirrors that of other palladium catalyzed cross-coupling reactions.10 11 irThere is an oxidative addition (A to B), followed by an exchange on palladium (B to C), and finally a reductive elimination (C to D and A). The main difference involves the exchange step. In a Suzuki, or Stille, reaction this step proceeds through a discrete transmetallation event, whereas... 

The final step in Scheme 69 is similar to that suggested for nickel or palladium-catalyzed cross-coupling of terminal alkynes with chlorophosphines to give phos-phinoalkynes. After P-Cl oxidative addition, Sonogashira-style formation of a metal-alkynyl group and P-C reductive elimination were proposed [123, 124]. 

The mechanism of the direct intramolecular Buchwald-Hartwig indole synthesis is that of a traditional palladium-catalyzed cross-coupling reaction and begins with loss of a ligand on palladium. Oxidative addition of an appropriately substituted Z-vinylhaloarene (1) generates intermediate 2. Deprotonation of 2 and displacement of a halide ligand sets up a reductive elimination on 3 to yield indole 4. 

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