Asymmetric organocatalytic Strecker-type reactions of aliphatic N,N-dialkylhydrazones

Abstract

The enantioselective organocatalytic Strecker-type reaction of aliphatic N,N-dialkylhydrazones is presented. Using trimethylsilyl cyanide (TMSCN) as the cyanide source, the reaction can be efficiently catalyzed by a tert-leucine-derived bifunctional thiourea to afford the corresponding hydrazino nitriles in good to excellent yields (50-96%) and moderate to good enantioselectivities, up to 86% ee. Further transformations of the nitrile functionality allow access to useful protected hydrazino acids and imidazolidinones. Interestingly, some of the hydrazino nitriles and their derivatives could be recrystallized in high recovery, yielding essentially pure enantiomers.

Transition-Metal-Free Trifluoromethylation of Aldehyde Derivatives with Sodium Trifluoromethanesulfinate

“…(E)-1,1-Dibenzyl-2-(cyclohexylmethylene)hydrazine (6bo). The title compound is known 36 and was prepared according to general procedure 1 using cyclohexanecarbaldehyde and 1,1-dibenzylhydrazine (0.55 g, 90% yield): 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7.29−7.21 (m, 10H, ArH), 6.44 (d, 1H, J = 8 Hz, CH), 4.22 (s, 4H, 2CH 2 ), 2.17−2.08 (m, 1H, CH), 1.69−1.66 (m, 5H, 2CH 2 +CH), 1.28−1.20 (m, 2H, CH 2 ), 1.14−1.06 (m, 3H, CH 2 +CH).…”

“…The title compound was prepared according to general procedure 2 using 6au and CF 3 SO 2 Na, and the crude product was purified by flash column chromatography (15:1 petroleum ether:ethyl acetate) to afford 7au (52 mg, 90% yield) as a slightly yellow oil exclusively with the configuration E: 1 H NMR (400 MHz, CDCl 3 ) δ (ppm) 7. 36 (E)-1-(4-Bromophenyl)-2,2,2-trifluoro-N-morpholinoethan-1imine (7av). The title compound was prepared according to general procedure 2 using 6av and CF 3 SO 2 Na, and the crude product was purified by flash column chromatography (15:1 petroleum ether:ethyl acetate) to afford 7av (56 mg, 83% yield) as a slightly yellow oil exclusively with the configuration E: 1 H NMR (400 MHz, CDCl 3 ) (ppm) 7.58−7.56 (m, 2H, ArH), 7.32−7.30 (m, 2H, ArH), 3.65−3.63 (m, 4H, 2CH 2 ), 3.01−2.99 (m, 4H, 2CH 2 ); 13 C NMR (100 MHz, CDCl 3 ) δ (ppm) 135.2 (q, 2 J C−F = 33.3 Hz), 134.7, 132.2, 130.4, 124.3, 121.0 (q, 1 J C−F = 272.9 Hz), 66.0, 54.3; 19 F NMR (376 MHz, CDCl 3 ) δ (ppm) −66.7; HRMS (ESI-Q-TOF) exact mass calcd for C 12 H 13 BrF 3 N 2 O [M + H] + 337.0085, found 337.0098.…”

Hydrazones as Singular Reagents in Asymmetric Organocatalysis

“…Considering the higher basicity of N , N ‐dialkylhydrazones over N ‐acyl hydrazones, we described an alternative Strecker‐type reaction based on thiourea organocatalysts . Using TMSCN as the reagent, the reaction with aliphatic N , N ‐dibenzylhydrazones 72 could be efficiently catalyzed by tert ‐leucine‐derived bifunctional thiourea XVII to afford the corresponding α‐hydrazinonitriles ( S )‐ 73 in good to excellent yields and moderate to good enantioselectivities (Scheme ).…”

N,N′-Bis[3,5-bis(trifluoromethyl)phenyl]thiourea: a privileged motif for catalyst development

“…Recently, during an investigation of an enantioselective Strecker-type reaction of aliphatic N,N-dialkylhydrazones using TMSCN as the cyanide source, Lassaletta and co-workers found that T1 efficiently accelerated the model reactions with respect to the background reaction in several solvents, thereby leading to the development of an asymmetric version. 36…”