Dehydrogenative Amide Synthesis

Fu Z, Lee J, Kang B, Hong SH (2012) Dehydrogenative amide synthesis azide as a nitrogen source. Org Lett 14 6028... 

Chen C, Verpoort F, Wu Q (2016) Atom-eeonomie dehydrogenative amide synthesis via ruthenium catalysis. RSC Adv 6(60) 55599-55607... 

Table 12.1 Conditions for amide synthesis via dehydrogenative coupling.

The initial synthesis of papaverine is due to Pictet, and fittingly enough involved as its key step the name reaction. Acylation of veratrylamine (109) with dimethoxyphenylacetylchlo-ride affords the amide (110). Cyclization by means of phosphorus oxychloride constitutes the same reaction and affords the dihy-droisoquinoline (111). Dehydrogenation by means of a noble metal catalyst affords papaverine (107). ... 

Synthesis of 216, an analog of the amide alkaloids, starting with ketone 214 was performed by Ishii et al. (176) (Scheme 33). The initial step involved the formation of cis secondary amine 215, which on N-formylation and dehydrogenation led to 216. Under Bischler-Napieralski conditions 216 could be recyclized to chelirubine (217). 

C-H activation remains an important topic for catalysis even after thirty years of intensive research. The potential shortcuts it offers for many present routes to a wide variety of chemicals that are produced will continue to inspire industrial and academic research [32], An interesting example involves the enantiospecific, coordination-directed C-H bond functionalisation in the synthesis of a natural product, rhazinilam, an anti-tumor agent. The resulting vinyl moiety obtained in the dehydrogenation was subsequently carbonylated to form a cyclic amide [33],... 

Synthesis of secondary amides via the oxidative coupling (dehydrogenation) of primary alcohols R CH3(OH) and primary amines R (CH3)NH3 to the amides... 

A synthesis of sevanine (16) by Bischler-Napieralski ring-closure of the amide (17) followed by hydrogenolysis and dehydrogenation has been reported.27 The alkaloid has also been prepared from papaverine by demethylation and methyl-enation with dichloromethane.27... 

A further method for the synthesis of the title compounds with only hydrogen as byproduct is the base-catalyzed dehydrogenative coupling (index D) of ammonia and tris(hydridosilylethyl)boranes, B[C2H4Si(R)H2]3 (R = H, CH3). Initially, the strong base, e.g. n-butyl lithium, deprotonates ammonia. The highly nucleophilic amide replaces a silicon-bonded hydride to form a silylamine and lithium hydride, which then deprotonates ammonia, resuming the catalytic cycle. Under the conditions used, silylamines are not stable and by elimination of ammonia, polysilazane frameworks form. In addition, compounds B[C2l-L Si(R)H2]3 can be obtained from vinylsilanes, H2C=CHSi(R)H2 (R - H, CH3), and borane dimethylsulfide. 

---