Rhodium ynamides

Tokunaga and Wakatsuki reported a one-pot indole synthesis from anilines and propargyl alcohols using Rn3(CO)j2 [5], and Nicholas and colleagues reported a Ru-catalyzed indole synthesis via the reductive annulation of nitros-oarenes with alkynes (equation 3) [6, 7]. Saa and coworkers described the Ru-catalyzed cycloisomerization of o-alkynylanihnes (equation 4) [8, 9]. Nissen and Detert reported a total synthesis of lavendamycin that featnred a Ru-catalyzed [2-f2-f2] cycloaddition of an o-alkynyl-ynamide, a method that was superior to rhodium catalysis both in terms of efficiency and regiochemistiy [10]. 

Scheme 10.132 Mechanistic rationaiization of the rhodium-cataiyzed carbozincation of ynamides [111].

Scheme 10.133 Microwave-assisted rhodium-catalyzed carbometallation of ynamides with arylboronic acids [112].

Clausine C (107) was synthesized in six steps with an overall yield of 40%, starting from commercially available iodoaniline 104. Notably, the yne-ynamide formation was realized though direct N-ethynylation of the corresponding tosylamide generated from 104 using the readily available alkynyliodonium salt 105. Thereafter, the rhodium-catalyzed crossed alkyne cyclotrimerization of 106 with methyl propri-olate furnished the corresponding crossed cycloaddition products in the ratio 4 1... 

Originally, the pyridine construction reaction was based on cobalt catalysis and restricted to the use of acetonitrile or alkyl nitriles as one of the cycloaddition partners. However, recent advancements in this area have led to the development of certain ruthenium or rhodium catalysts, allowing the use of methylcyanoformate as an electron-deficient nitrile component in crossed [2 - - 2 - - 2]-cycloaddition reactions [39]. From the point of view of applications, the use of methylcyanoformate in transition-metal-catalyzed pyridine formation reaction is quite beneficial because the ester moiety might serve as a functional group for further manipulations. It might also serve as a protective group of the cyanide moiety, because cyanide itself cannot be used in this reaction. These considerations led to the design of a quite flexible approach to substituted 3-(130)- and y-carbolines (131) based on transition-metal-catalyzed [2 -f 2 -I- 2] cycloaddition reactions between functionalized yne-ynamides (129) and methylcyanoformate (Scheme 7.28) [40]. 

Hsung et al. reported subsequently that when achiral ynamides 103 and a chiral rhodium(I) catalyst were employed instead of chiral ynamides 101 and Wilkinson s... 

Interestingly, Lam has described a synthesis of enamides via rhodium-catalyzed carbozincation of ynamides [175]. When applied to dialkenylzinc compounds, this reaction leads to the regio- and stereoselective formation of 1-amidodienes 224 (Scheme 87). The regioselectivity of the reaction was explained by the possible formation of a chelated complex 223. 

The ynamides are multipurpose synthetic blocks that are very promising reactants in light of this methodology [72, 73]. Tanaka has carried out the enantioselective synthesis of axially chiral anilides by the rhodium-catalyzed [2-I-2-I-2] cycloaddition of 1,6-diynes 2.93 to trimethylsilyly-namides 2.94 to form the corresponding axially chiral anilides 2.95 with high enantioselectivity. The anilide yield depends on the substituents in the ynamide (Scheme 2.33) [74]. 

Scheme 2.33 Rhodium-catalyzed enantioselective [2-1-2-1-2] cycloaddition of 1,6-diynes with ynamides.

Scheme 2.34 Rhodium(I)-catalyzed [2+2+2] cycloadditions of ynamides 2.96 in the synthesis of amide-substituted chiral biaryls 2.98 and 2.99.

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