Pd-mediated coupling

The Pd-mediated coupling involving organomercury and alkenes is useful for the synthesis of C-5 substituted 2 -deoxyribonucleosides[376]. The ethylur-idine 415 is prepared by the reaction of the 5-chloromercuriuridine 414 with... 

Several groups have developed procedures for Pd-mediated coupling based on this general chemistry. The variety of such procedures and the range of compounds for which they are applicable suggest that Pd-calalysed coupling is currently the most versatile method for introduction of 2-substituents which cannot be prepared directly from organolithium intermediates. 

Ley and Schanze [14, 68] have synthesized a series of PPE-type polymers that contain/ac-(5,5 -diethynyl-2,2 -bipyridine)Re(I)(CO)3Cl as part of the n-conju-gated main chain by a Pd-mediated coupling reaction, as illustrated in Scheme 9. The polymers differ with respect to the mole ratio of 4,4 -diethynylbiphenyl (59) and (5,5 -diethynyl-2,2 -bipyridine)Re(l)(00)301 (58) used in the polymerization reaction mixture. Four different polymers have been prepared and contain 0 (Po), 10 (Pio), 25 (P25), and 50 (P50) mol% of the Re(I) repeat units in the polymer chain, respectively (Scheme 9). 

Pd-Mediated Coupling in Organic Synthesis Recent Milestones... 

Stephen L. Buchwald at MIT has reported (Org. Lett. 2004, 6, 4809) a complementary approach. Enantioselective conjugate reduction of the inexpensive 3-methylcyclopentenone 4 led to the silyl enol ether 5, Pd-mediated coupling of which with the aryl halide gave the product 6. 3-Methylcyclohexenone gave the analogous product in 84% . 

A common application of aryl halides is Pd-mediated coupling to form C-C bonds. Graham Meek of Chirotech Technology Ltd., Cambridge, UK has found (Tetrahedron Lett. 2004,45, 9277) that the enamide 6 participates efficiently in Heck coupling. The product 7 is an excellent substrate for enantioselective hydrogenation, to give 8. 

The specific construction of trisubstituted alkenes is a continuing challenge. Shigeru Nishiyama of Keio University has described (Tetrahedron Lett. 2004, 45, 8273) the specific bromination-dehydrobromination of the allylic ester 9, delivering 10 as a 60 1 mixture of geometric isomers. Pd-mediated coupling led to the ester 11. 

Pd-mediated coupling of 50 could, in principle, terminate via p-elimination of either the C8 or C12 hydrogens. However, only the latter was observed. In our case, pentacycle 46 has only the C8 hydrogen available, and the normal course of the Heck reaction would be expected to produce pyridone 58 (Scheme 30). If p-elimination proved slow, an added hydride source might capture the palladium a-complex and provide the desired formal conjugate addition product 51. 

Zhang, H.-C. Daves, G. D. Water facilitation of Pd-mediated coupling reactions. Organometallics 1993, 12,1499-1500. 

This aUows the cross-coupling of an aryUialide (2) with an aryltrialkyl stannane in presence of a boronic ester. The latter remains unreactive because it would need to be hydrolyzed to a boronate to be suited for Pd-mediated couplings. Progression in a couphng cycle would further require OH , CO , or F , not present under the used StiUe couphng conditions [178,179]. The Stille conditions proved very useful for affording many aryl-aryl [1, 4, 180, 181, 182], vinyl-aryl [9, 161, 183, 184] and also aUcyl-aryl [185] compounds bearing hydrolytically labile moieties. The commonly used reactivities of aryl or vinyl halide components are like those in the... 

Zn alkyls, generated in situ, are very versatile reagents for alkyl-alkyl, alkyl-aryl and aryl-aryl couplings [73]. Arylzinc bromides and benzylzinc iodides may serve as more reactive substitutes for boronates or stannanes in Pd-mediated couplings. 

Palladium catalysis has been found to promote the Ullman reaction, and may also influence the course of the reaction. Under typical Ullman conditions homo-coupling (349, 350) is favored in the reaction between 3-iodopyridine and bromo-nitrobenzenes, whereas the presence of Pd(PPh3)4 favors cross-coupling (348). Both 2- and 4-iodopyridines and 2-bromopyridine undergo Pd-mediated coupling (84JOC5237 93TL3421). 

PDC (pyridinium dichromate), 360 PDC, 362 PdCl2(PPh3)2, 229 Pd-mediated coupling, 157 Pearlman s catalyst, 189, 378, 386 4-pentenoyl chloride, 451 peroxisome-proliferator-activated receptor, 358 Peterson elimination, 278 Peterson olefination, 453... 

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