Anilide, axially chiral

Taguchi and colleagues189 studied the reactions of axially chiral maleimide and anilide derivatives 298 and 300 with cyclopentadiene (equation 83). The reaction of 298 with cyclopentadiene, catalyzed by diethylaluminum chloride, proceeded quantitatively with almost complete endo and diastereofacial selectivities to give 299 and 301, respectively. The reaction of 300 with cyclopentadiene was catalyzed by iodine and proceeded via a cationic iodocyclization intermediate. The reaction afforded a mixture of endo and exo isomers in a ratio of endo/exo = 97/3, the endo isomer being obtained with 97% de. 

Interestingly, (R,R)-3, (R)-27 and (,V)-4 gave (f )-axially chiral anilide chromium complex, involving lithiation at Me" and subsequent quenching with electrophile, whereas the opposite result is observed with N,7V-diethyl-2,6-dimethylbenzamide chromium complex. This difference in stereochemical outcome was attributed to the positioning of the carbonyl... 

These high stereoselectivities bode well for the use of axially chiral anilides as chiral auxiliaries. 

Scheme 7.24 Enantiospecific Mizoroki-Heck cyclization of axially chiral anilides.

A binaphthyl-based PTC (S)-21 was found to be an effective catalyst for the catalytic asymmetric synthesis of axially chiral o-iodoanilides. M-allevlation of achiral o-iodoanilines catalysed by (S)-21 gave axially chiral o-iodoanilides in high enantioselectivity (Scheme 17.27). In this reaction, the large steric difference between the ort/zo-substituents (methyl and iodo groups) on anilides was necessary to achieve high enantioselectivity. 

ENANTIOSELECnVE SYNTHESIS OE AXIALLY CHIRAL ANILIDES AND BEZAMIDES... 

For the simultaneous construction of biaryl- and anilide-based axial chiralities, Tracey et al. investigated the RhCl(PPh3)3-catalyzed diastereoselective [2-I-2-I-2] cycloaddition of terminal 1,6-diynes 100 with ynamides 101, bearing chiral auxiliaries. Although the desired axially chiral anilides 102 were obtained in good to high yields, the diastereoselectivities observed were low to moderate (Scheme 9.35) [31]. 

Cationic rhodium(I)/chiral biaryl bisphosphine complexes are suitable for the enantioselective [2-I-2-1-2] cycloaddition reactions between electron-rich alkynes and electron-deficient unsaturated compounds (alkynes, nitriles, and isocyanates). Alkynylcarbonyl compounds, alkynylphosphonates, and alkynylphosphine oxides are the best-suited electron-deficient unsaturated compounds for these catalysts. These complexes are also able to catalyze the highly enantioselective synthesis of axially chiral anilides and bezamides. 

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]. 

Tanaka, K., Takeishi, K. and Noguchi, K. (2006) Enantioselective synthesis of axially chiral anilides through rhodium-catalyzed [2+2+2] cycloaddition of 1,6-diynes with trimethylsilylynamides. Journal of the American Chemical Society, 128(14), 4586-4587. 

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