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Important organocatalysts for asymmetric synthesis

Recently in our blog “Bifunctional Chiral Squaramide Organocatalysts”, we reported the squaramide hydrogen bond donor catalysts and now we would like to direct attention to another family of hydrogen-bonded donor organocatalyst based on thiourea. Generally, it is believed that despite the structural similarities between squaramides and thioureas (Fig. 1), the squaramides exhibit better catalytic activity in certain organic reactions due to their ability to form stronger hydrogen bonds with  substrates bearing nitro, carbonyl, imino, nitrile and halide functionalities. However,  the pioneering research led by the Jacobsen’s group in 2004 [2-3], chiral thiourea based derivatives became an important hydrogen bond donor catalyst in asymmetric synthesis. In addition, the easy synthesis of thiourea products and their promising catalytic activity and selectivity with different anions are key factors for the construction of complex molecular structures and chiral biologically active compounds [4-9].

Fig. 1. Comparison of squaramide and thiourea scaffolds for chiral organocatalysts.

The major difference between thioureas and squaramides is the relative distance and spacing between the two N–H groups. The distance between the two N–H groups of a squaramide (2.72 Å) is approximately one third larger than that in a thiourea (2.13 Å) [1]. Similarly to squaramides, thioureas also display bifunctional behavior determined by N–H donor groups and chiral moieties.

Strem offers a wide range of thiourea based catalysts providing set of convenient synthetic tools for asymmetric synthesis that includes nucleophilic conjugate additions, Friedel-Crafts alkylations, benzoylations, Baylis-Hillman reactions, Mannich reactions, methanolysis and many others. A noteworthy application is the reported photochemical reactivity of thiourea as oraganocatalysts [10-11].

A list of thiourea products with other chiral organocatalysts from Strem can be reviewed in our High Purity Chiral Reagents booklet.

References:

1. Chem. Rec. 2017, 17, 994.
2. J. Am. Chem. Soc. 2004, 126, 4102.
3. J. Am. Chem. Soc. 2008, 130, 7198.
4. Chem. Commun., 2008, 2499.
5. Chem. Pharm. Bull., 2010, 58, 593.
6. Chem. Eur. J. 2011, 17, 6890.
7. Chem. Soc. Rev., 2013, 42, 774.
8. Chem. Rev. 2014, 114, 2390.
9. Coord. Chem. Rev., 2015, 295, 80.
10. Angew. Chem. Int. Ed. 2014, 53, 5604.
11. Nature, 2018, 554, 41.

Related Products:

07-6300 N-[3,5-Bis(trifluoromethyl)phenyl]-N'-[(1S,2R)-2,3-dihydro-2-hydroxy-1H-inden-1-yl]thiourea, 95%, (99% ee) (949480-57-3)

07-6312 N,N'-(1R,2R)-1,2-Cyclohexanediylbis[N'-[3,5-bis(trifluoromethyl)phenyl]thiourea], 98%, (99% ee) (743458-79-9)

07-7130 (R)-1-[3,5-Bis(trifluoromethyl)phenyl]-3-[1-(dimethylamino)-3-methylbutan-2-yl]thiourea, 98%, (99% ee) (1048692-61-0)

07-0821 N,N'-[(1R,2R)-1,2-Diphenyl-1,2-ethanediyl]bis[N'-[3,5-bis(trifluoromethyl)phenyl]thiourea], 98%, (99% ee) (1012051-90-9)

07-8020 N,N'-[(1S,2S)-1,2-Diphenyl-1,2-ethanediyl]bis[N'-[3,5-bis(trifluoromethyl)phenyl]thiourea], 95%, (99% ee) (1416334-72-9)

07-6319 N-[3,5-Bis(trifluoromethyl)phenyl]-N'-[(1S,2S)-2-(1-piperidinyl)cyclohexyl]thiourea, 98%, (99% ee) (1244061-69-5)

07-6318 N-[3,5-Bis(trifluoromethyl)phenyl]-N'-[(1R,2R)-2-(1-piperidinyl)cyclohexyl]thiourea, 98%, (99% ee) (1289514-24-4)

07-6320 N-[(1R,2R)-2-[Bis(phenylmethyl)amino]cyclohexyl]-N'-[3,5-bis(trifluoromethyl)phenyl]thiourea, 98%, (99% ee) (1240466-16-3)

07-6321 N-[(1S,2S)-2-[Bis(phenylmethyl)amino]cyclohexyl]-N'-[3,5-bis(trifluoromethyl)phenyl]thiourea, 98%, (99% ee) (1233369-39-5)

07-1346 N-[3,5-Bis(trifluoromethyl)phenyl]-N'-[(1S,2S)-2-(dipentylamino)cyclohexyl]thiourea, 98%, (99% ee) (1429516-79-9)

07-1345 N-[3,5-Bis(trifluoromethyl)phenyl]-N'-[(1R,2R)-2-(dipentylamino)cyclohexyl]thiourea, 98%, (99% ee)

07-1350 1-[3,5-Bis(trifluoromethyl)phenyl]-3-[(1R,2R)-2-(pyrrolidin-1-yl)cyclohexyl]thiourea, 98%, (99% ee) (1314743-49-1)

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