Silver(I)-Catalyzed Atroposelective Desymmetrization of N-Arylmaleimide via 1,3-Dipolar Cycloaddition of Azomethine Ylides: Access to Octahydropyrrolo[3,4-c]pyrrole Derivatives

Abstract

A highly efficient Ag(I)-catalyzed atroposelective desymmetrization of N-(2-t-butylphenyl)maleimide via 1,3-dipolar cycloaddition of in situ generated azomethine ylides has been established successfully, affording a facile access to a series of biologically important and enantioenriched octahydropyrrolo[3,4-c]pyrrole derivatives in generally high yields (up to 99%) with excellent levels of diastereo-/enantioselectivities (up to 99% ee, >20:1 dr). Subsequent transformations led to fascinating 2H-pyrrole and polysubstituted pyrrole compounds without loss of stereoselectivity. The absolute configuration of the generated chiral axis has been unambiguously identified as (M) through single-crystal X-ray diffraction analysis. Furthermore, on the basis of the comprehensive experimental results and the absolute configuration of one of the cycloadducts, the origin of the stereoselectivity was proposed to be attributed to the steric congestion imposed by the bulky PPh2 group of the chiral ligand and the tert-butyl group of N-(2-t-butylphenyl)maleimide. The possible hydrogen bond interaction between the NH2 group of the chiral ligand and one of the carbonyl groups of N-(2-t-butylphenyl)maleimide is considered to facilitate stabilizing the transition state.

An efficient and facile access to highly functionalized pyrrole derivatives

“…Encouraged by the achievements on catalytic asymmetric 1,3-dipolar cycloaddition to build octahydropyrrolo[3,4- c ]pyrrole frameworks [7,9], we screened the optimal reaction conditions for preparing the racemic pyrrolidine 11a using N -methylmaleimide ( 10a ) as the simple dipolarophile without any chiral catalysts/ligands. To our delight, in the presence of 10 mol % of AgOAc, the reaction reached almost completion in CH 2 Cl 2 within 1 h at room temperature and afforded the desired cycloadduct in moderate yield (64%, Table 2, entry 1).…”

“…As expected, toluene as solvent improved the reaction outcome to afford 12a in a good yield up to 71% (Table 3, entry 2). Subsequently, reducing the amount of DDQ (2 equiv) led to a significantly decreased yield (Table 3, entry 3), and also the addition of silica gel [9] as an additive had no considerable effect on the yield (Table 3, entry 4 vs entry 2). The results demonstrated that using 4 equiv DDQ in toluene were the best conditions for this oxidation protocol.…”

Silver‐Catalyzed Diastereoselective Synthesis of Spirocyclic Pyrrolidine‐Lactones by 1,3‐Dipolar Cycloaddition

“…for C 23 H 22 N 2 O 4 : 390.1580, found 390.1576. hydro-2H,4′H-spiro[furan-3,1′-pyrrolo[3,4-c 14, 349 (14), 348 (29), 336 (16), 335 (97), 334 23, 333 (100), 322 (12), 321 (16), 320 10, 319 (11), 281 10), 241 (17, 236 (11), 115 13, 89 10 28.7 = -80.9 (c 0.58, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ) δ H = 1.55 (d, J = 6.1 Hz, 3H, CH 3 ), 2.02 (t, J = 12.5 Hz, 1H, CH 2 ), 2.79 (dd, J = 12.5, 4.5 Hz, 1H, CH 2 ), 2.86 (s, 3H, CH 3 ), 3.41 (d, J = 7.6 Hz, 1H, CCH), 3.98 (t, J = 7.7 Hz, 1H, NCHCH), 4.80 (d, J = 7.7 Hz, 1H, NCH), 4.60-4.87 (m, 1H, CHCH 3 ), 7.20-7.24 (m, 1H, ArH), 7.30-7.34 (m, 1H, ArH), 7.46-7.49 (m, 1H, ArH), 7.60-7.63 (m, 1H, ArH) ppm; 13 C NMR (CDCl 3 ) δ C = 20.5 (CHCH 3 ), 25.4 (NCH 3 ), 45.6 (CH 2 ), 47.5 (CHCO), 53.5 (CHCO), 63.2 (NCH), 69.2 (NC), 73.6 (CHCH 3 ), 123.6, 127. 0,127.8,129.9,132.8,135.2 (ArC) 3S,3′R,3a′S,5R,6a′R)-5,5′-Dimethyl-3′-(p-tolyl)hexahydro-2H,4′Hspiro[furan-3,1′-pyrrolo [3,4-c (CCH 3 ), 25.3 (NCH 3 ), 46.2 (CH 2 ), 51.0 (NCHPhCH), 54.6 (NCCH), 64.6 NCHPh), 69.7 (NC), 73.6 (CHCH 3 ), 126.…”

“…(3S,3′R,3a′S,5R,6a′R) 26.2 = -68.5 (c 0.71, CHCl 3 ); 1 H NMR (300 MHz, CDCl 3 ) δ H = 1.55 (d, J = 6.1 Hz, 3H, CH 3 ), 1.97 (dd, J = 12.3, 11.0 Hz, 1H, CH 2 ), 2.44 (s, 3H, CCH 3 ) 2.74 (dd, J = 12.5, 4.6 Hz, 1H, CH 2 ), 2.85 (s, 3H, NCH 3 ), 3.39 (d, J = 7.7 Hz, 1H, CCH), 3.69 (t, J = 7.9 Hz, 1H, NCHCH), 4.7 (d, J = 8.1 Hz, 1H, NCH), 4.77-4.87 (m, 1H, CHCH 3 ), 7.20-7.35 (m, 4H, ArH) ppm; 13 C NMR (CDCl 3 ) δ C = 19.8 (CH 3 ), 20.5 (CH 3 ), 25.3 (NCH 3 ), 45.9 (CH 2 ), 48.5 (CHCO), 54.2 (CHCO), 61.1 (NCH), 69.2 (NC), 73.6 (CHCH 3 ), 124. 8, 126.4, 128.2, 130.5, 134.2, 135.6 (ArC), 173.8 (CO), 174.6 (CO), 175.0 (CO) ppm; IR (ATR) ν: 3022,2977,2932,1773,1699,1434,1285,1198, 1095 cm -1 ; MS (EI): m/z 320 (16), 278 (43), 276 (22), 261 (100), 248 (18), 247 (22), 209 (11), 164 (10), 96 (12); HRMS calcd. for C 18 H 20 N 2 O 4 : 328.1423, found 328.1430.…”

“…However, homoserine lactone 16 derived 1,3dipole has been used in multiple non-asymmetric processes with several common dipolarophiles, [12] methyleneindolinone derivatives, [13] arylidenemalonates. [14] In the case of enantioselective silver(I)-catalyzed 1,3-DC with common dipolarophiles, [15,16] 3-methyl-4-nitro-5-alkenyl-isoxazole, [17] and nitro-benzylation with trifluoroacetic acid as the solvent and triethylsilane as the reducing agent. Chiral lactone 23a was isolated in 94 % yield and 98:2 dr.…”