Palladium-catalyzed dehydrogenation

Alternatively, 3-picoline is produced by vapor phase cyclization of 2-methyl-pentane-1,5-diamine (Fig. 2.25) over, for example, H-ZSM-5 followed by palladium-catalyzed dehydrogenation [78]. This diamine is a by-product of the manufacture of hexamethylenediamine, the raw material for nylon 6,6, and these two reactions are key steps in the Lonza process for nicotinamide production (see Chapter 1) [79]. 

Mechanistically, palladium-catalyzed dehydrogenations have been shown to proceed according to Scheme 25, in which the initially formed ir-complex (45) learranges to a a-complex (46) prior to the elimination of palladium hydride. - ... 

Thiepines have been reported as examples in methodology reported for formation of analogous azepines and oxepines (14JOC11873,140BC7774). One method that was unique to thiepines was the sulfoxide-directed C-H activation of arenes in a palladium-catalyzed dehydrogenative cychzation yielding dibenzothiepines (140L4574). 

Palladium-catalyzed dehydrogenative cis double phosphorylation of 1-octyne with the /7-phosphonate (88) leading to (Z)-l,2-bisphosphoryl-octene (89) has been sueeessfully carried out by Han et al (Scheme 28). p-Aryl-p-ketophosphonates (90) have been efficiently prepared in good yields using the TBAA/H3P04-mediated acylation of electron-rich arenes with phosphonoacetic acids. The conditions enabled preparation of (90) without use of strong bases, cryogenics or anhydrous and inert atmosphere. 

Use of pivalic acid (PivOH) as a solvent with 10 mol % K2CO3 was highly effective for the acceleration of palladium-catalyzed dehydrogenative intramolecular coupling reaction [35]. For example, electron-rich diarylamines 71 underwent the cyclization smoothly to give 72 in much higher yields that those of the same reaction carried out in AcOH (Table 22.3). The examples illustrated in Table 22.3 are a synthesis of... 

Intramolecular arylation of triazoles by a palladium-catalyzed dehydrogenative pathway has also been reported. This closely related transformation enables efficient preparation of tricyclic triazoles without any prefunctionalization of arylating agents [97]. Under optimized conditions, this coupling can be conducted at ambient air pressure (Scheme 42). 

Han L-B, Ono Y, Shimada S (2008) Palladium-catalyzed dehydrogenative cis double phosphorylation of alkynes with H-phosphonate leading to (Z)-bisphosphoryl-l-alkenes. J Am Chem Soc 130 2752-2753... 

Among the important reagents for which preparative procedures are given are 2,2 -bipyridine (by nickel directed and catalyzed dehydrogenation of pyridine p. 5), formamidine acetate (p. 39), phenyltrichloromethylmercury (p. 98), and trimethyl- and triethyloxonium fluoroborate (pp. 120, 113). The preparation of palladium catalyst ( Lindlar ) for the selective reduction of acetylenes is described (p. 89), as is the use of di-phenyliodonium-2-carboxylate, as a precursor of benzyne in the synthesis of 1,2,3,4-tetraphenylnaphthalene (p. 107). 

After the failure of the direct synthesis of the completely unsaturated heterocycle 34, an attempt was made to synthesize the partially saturated cyclopenta[t]-l, 2-diazcpine, which then could be dehydrogenated to the 5,6-diazaazulene 34. However, this approach by starting with a 1,2-diazepine ring 36 (made successfully by following published method) and its [3+2] palladium-catalyzed cycloaddition with allyl chlorosilane 35 to the bicyclic diazepine 37 failed (Scheme 8). 

The palladium-catalyzed intramolecular addition of an amine to an alkene is an efficient route to nitrogen heterocycles. The products often undergo further dehydrogenation under the reaction conditions to form fully aromatic... 

Instead of a second or third alkyne, an alkene C=C double bond may be incorporated into the cyclotrimerization reaction. Iron [65], rhodium [66], nickel [67], palladium [68], or cobalt [69] catalysts have been used to form cyclohexa-dienes. However, the preparative use of this catalytic co-cyclization is disturbed by consecutive side reactions of the resulting dienes such as cycloaddition or dehydrogenation. Itoh, Ibers and co-workers [70] have reported the straight palladium-catalyzed co-cyclization reaction of C2(C02Me)2 and norbomene (eq. (24)). 

Scheme 9.48 Palladium-catalyzed homo-dehydrogenative coupling of the 2-arylpyridine 173.

More promising results were obtained for cross-dehydrogenative arylations with heteroarenes, since pronounced differences in reactivities gave improved chemos-electivity. In elegant studies it was shown that palladium-catalyzed oxidative arylations of indoles could be accomplished with unactivated arenes, which were used as solvents, in the presence of Cu(OAc)2 as terminal oxidant [130]. Notably, these reactions proceeded with high regioselectivities, leading predominantly to arylations at position C-3 (Scheme 9.51). 

Scheme 9.52 Palladium-catalyzed cross-dehydrogenative arylation of the indole 184 at position C-2.

Scheme 9.53 Palladium-catalyzed cross-dehydrogenative arylation.

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