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Chemical Synthesis

Jacobsen Thioureas

New Versatile Organocatalysts

In 2002, Jacobsen’s group first reported the application of thiourea organocatalyst 1 (693421) in the asymmetric Strecker reaction. Since that initial report, Jacobsen's group have developed a range of chiral thioureas that are versatile, effective organocatalysts. A range of latent nucleophiles can be added to mostly imine-type electrophiles in excellent enantiomeric excesses and, in general, with a broad substrate scope. Strecker, hydrophosphonylation, Mannich, cyanosilylation, and Pictet–Spengler reactions are all possible, indicating these catalysts have great potential as general catalysts for asymmetric organic synthesis.


 

 

Representative Applications


 

Strecker Reaction

The thiourea organocatalyst 693421 was reported by Jacobsen to have a very broad scope in the Strecker reaction. Both aldimines and ketoimines both underwent hydrocyanation with very high enantioselectivities in the presence of 1 mol % the catalyst.


Hydrophosphonylation of Imines

Similarly, imine hydrophosphonylation occurred in the presence of 10 mol% of the catalyst. The reaction was particularly effective with electron-withdrawing ester substituents on the phosphite, and was tolerant of a wide variety of aldimines.


Mannich Reaction

Mannich reactions of Boc-protected imines have also been reported by the Jacobsen group. A wide variety of N-Boc arylimines underwent addition with good to excellent yields and enantioselectivities when catalyzed by thiourea organocatalysts. Again the organocatalytic reaction shows excellent substrate tolerance, particularly for heterocyclic substrates.


Another variant of the thiourea organocatalyst is effective in the acyl-Mannich reaction, providing a route to enantioenriched heterocycles from aromatic starting materials and trichloroethyl chloroformate(TrocCl).


Cyanosilylation

More recently, the cyanosilylation of ketones has also been achieved using a slightly different version of the thiourea organocatalyst. The reaction proceeds for ketones and aldehydes as well in high yields and enantiomeric excesses. In addition, the catalyst can be recovered in near quantitative yield by silica gel chromatography.


Acyl-Pictet-Spengler Reaction


Product Information


 

Product Number Product Name Structures Add to Cart
693316 (S)-2-[[3,5-Bis(trifluoromethyl)phenyl]thioureido]-N-benzyl-N,3,3-trimethylbutanamide
693340 (2S)-3,3-Dimethyl-2-[[(1R,2R)-2-(2-methyl-5-phenyl-1-pyrrolyl)cyclohexyl]thioureido]-N,N-bis(2-isobutyl)butanamide
693413 (S)-2-[[(1R,2R)-2-Aminocyclohexyl]thioureido]-N-benzyl-N,3,3-trimethylbutanamide
693421 3-[(E)-[[(1R,2R)-2-[[(1S)-1-[(Dimethylamino)carbonyl]-2,2-dimethylpropyl]thioureido]cyclohexyl]imino]methyl]-5-(tert-butyl)-4-hydroxyphenyl pivalate
693464 (S)-2-[3-[(1R,2R)-2-(Dipropylamino)cyclohexyl]thioureido]-N-isopropyl-3,3-dimethylbutanamide
693472 (S)-2-[[(1R,2R)-2-[[[3,5-Bis(tert-butyl)-2-hydroxyphenyl]methylene]amino]cyclohexyl]thioureido]-N-benzyl-N,3,3-trimethylbutanamide