Synthesis of 2‐(3‐(3,5‐bis(trifluoromethyl)phenyl)thioureido)‐3‐((dimethylamino)methyl)camphor organocatalysts

Abstract

In a stereo-divergent synthesis, three novel camphor-derived bifunctional thiourea organocatalysts 7-9 have been prepared in five steps starting from (+)-camphor. In addition, borneol-derived bifunctional thiourea organocatalysts 19/19' have been prepared in three steps from (1S)-(+)-camphorquinone. Novel organocatalysts 7-9, 19/19' have been evaluated in a model reaction of Michael addition of dimethyl malonate to trans-β-nitrostyrene with low to moderate enantioselectivities (20%-60% ee). Configuration of all novel compounds has been meticulously determined using nuclear magnetic resonance (NMR) techniques.

Synthesis of Novel Camphor‐Derived Bifunctional Thiourea Organocatalysts

“…Despite the fact that camphor is one of nature's privileged scaffolds readily available in both enantiomeric forms and that camphor undergoes a wide variety of chemical transformations which functionalize, at first glance, inactivated positions, 24,25 demonstrated in the preparation of a wide variety of compounds ranging from natural products 24,25 to chiral auxiliaries, 26,27 ligands in asymmetric synthesis, [28][29][30][31][32] nuclear magnetic resonance (NMR) shift reagents, 33 etc., only a few ketopic acid-derived thiourea-prolinamide bifunctional organocatalysts have been prepared. 36 In continuation of our research of 3,5-bis(trifluoromethyl) phenyl thiourea-derived bifunctional organocatalysts with camphor as the exclusive chiral framework, we herein report our attempts to prepare camphor-derived thiourea bifunctional organocatalysts of type B-D (Fig. 36 In continuation of our research of 3,5-bis(trifluoromethyl) phenyl thiourea-derived bifunctional organocatalysts with camphor as the exclusive chiral framework, we herein report our attempts to prepare camphor-derived thiourea bifunctional organocatalysts of type B-D (Fig.…”

“…34,35 Previously, we reported the preparation and performance of camphor 1,3-diamine-derived bifunctional organocatalysts of type A. 36 In continuation of our research of 3,5-bis(trifluoromethyl) phenyl thiourea-derived bifunctional organocatalysts with camphor as the exclusive chiral framework, we herein report our attempts to prepare camphor-derived thiourea bifunctional organocatalysts of type B-D (Fig. 1), and their performance in a model reaction of Michael addition of dimethyl malonate to trans-β-nitrostyrene.…”

Stereodivergent Synthesis of Camphor-Derived Diamines and Their Application as Thiourea Organocatalysts

“…Within our continuing study on camphor-based diamines as potential organocatalyst scaffolds with camphor as the exclusive chiral framework, we previously reported on camphor C2-, C3-, and C8-derived 1,2-, 1,3-, and 1,4-diamines [ 40 , 41 , 42 ]. The corresponding noncovalent thiourea organocatalysts have been evaluated for the 1,4-addition of dimethyl malonate to trans -β-nitrostyrene.…”

“…The corresponding noncovalent thiourea organocatalysts have been evaluated for the 1,4-addition of dimethyl malonate to trans -β-nitrostyrene. Reaction with 1,2- and 1,4-diamine-derived catalysts resulted in low enantioselectivity (er up to 61.5:38.5) [ 40 ], while reaction with 2- endo -3- endo -1,3-diamine-derived catalyst gave the addition product with moderate enantioselectivity (80:20 er) [ 42 ]. On the other hand, the camphor-1,3-diamine-derived squaramide organocatalyst was highly effective in conjugative additions of 1,3-dicarbonyls to trans -β-nitrostyrenes [ 43 , 44 ].…”

Synthesis and Reduction of 10-Phthalimidocamphor Oxime

“…1,2 All of the above makes camphor a very desirable starting compound for the preparation of a wide variety of products 3 ranging from natural products 1,2 to chiral auxiliaries, 4,5 ligands in asymmetric synthesis, [6][7][8][9][10] organocatalysts, 11 and NMR shift reagents. 12 Within our continuing study on camphor-based diamines as potential organocatalyst scaffolds, [13][14][15] we recently reported on the synthesis of a novel type of 1,3-diamine-derived bifunctional squaramide orga nocatalysts A prepared from 10-iodocamphor and their application as highly efficient catalysts in Michael additions of 1,3-dicarbonyl nucleophiles to trans-β-nitrostyrenes. 16 10-Iodocamphor 17 has seen surprisingly limited appli cation as the starting compound, [18][19][20][21][22][23][24] although, it can easily be prepared in sufficient quantities from (1S)-(+)-10-camphorsulfonic acid.…”