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Chemical Synthesis

Macmillan Imidazolidinone Organocatalysts

 

Metal-free Asymmetric Catalysis

Developed by Professor David MacMillan at Caltech, imidazolidinone-based OrganoCatalysts™ are designed to serve as general catalysts for a variety of asymmetric transformations. The first highly enantioselective organocatalytic Diels-Alder reaction using (5S)-2,2,3-trimethyl-5-phenylmethyl-4-imidazolidinone monohydrochloride was reported by MacMillan in his pioneering work in 2000 (Scheme 1).1 The activated iminium ion, formed through condensation of the imidazolidinone and an α,β-unsaturated aldehyde, underwent reaction with various dienes to yield [4+2]-cycloadducts in excellent yields and enantioselectivities.

 

 
Other organocatalytic transformations such as 1,3-dipolar cycloadditions,2 Friedel-Crafts alkylations,3 α-chlorinations,4 α-fluorinations,5 and intramolecular Michael reactions6 were reported using MacMillan’s Imidazolidinone OrganoCatalysts™, all proceeding with high levels of enantioselectivity (Scheme 2).

 

 

MacMillan found an optimized structure in (2S,5S)-(−)-2-tert-butyl-3-methyl-5-benzyl-4-imidazolidinone for the Friedel-Crafts alkylation of indoles (Scheme 3). 6,7

 


 

The synthetic utility of this concept was later demonstrated in the total synthesis of (–)-flustramine B, a biologically active pyrroloindoline-containing alkaloid (Scheme 4).

 

 

Sigma-Aldrich, in collaboration with Materia, Inc., is pleased to offer the following six imidazolidinone OrganoCatalysts™.

 

Product # Product Name/Description Structure Add to Cart
674575 MacMillan Imidazolidine OrganoCatalyst™ Kit I -
661910 (R)-(-)-2-(tert-Butyl)-3-methyl-4-oxoimidazolidinium trifluoroacetate
661902 (S)-(+)-2-(tert-Butyl)-3-methyl-4-oxoimidazolidinium trifluoroacetate
668842 (2R,5R)-(+)-5-Benzyl-3-methyl-2-(5-methyl-2-furyl)-2-imidazolidinone
668540 (2S,5S)-(-)-5-Benzyl-3-methyl-2-(5-methyl-2-furyl)-2-imidazolidinone
569763 (5S)-2,2,3-Trimethyl-5-phenylmethyl-4-imidazolidinone monohydrochloride
663069 (5R)-2,2,3-Trimethyl-5-phenylmethyl-4-imidazolidinone monohydrochloride
663107 (2S,5S)-(−)-2-tert-Butyl-3-methyl-5-benzyl-4-imidazolidinone
663093 (2R,5R)-(+)-2-tert-Butyl-3-methyl-5-benzyl-4-imidazolidinone
663077 (5R)-2,2,3-Trimethyl-5-benzyl-4-imidazolidinone dichloroacetic acid
663085 (5S)-2,2,3-Trimethyl-5-benzyl-4-imidazolidinone dichloroacetic acid


References:
1. Ahrendt, K. A.; Borths, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122, 4243.
2. Jen, W. S.; Wiener, J. J. M.; MacMillan, D. W. C. J. Am. Chem. Soc. 2000, 122, 9874.
3. Paras, N. A.; MacMillan, D. W. C. J. Am. Chem. Soc. 2001, 123, 4379-4371.
4. Brochu, M. P.; Brown, S. P.; MacMillan, D. W. C. J. Am. Chem. Soc. 2004, 126, 4108.
5. Beeson, T. D.; MacMillan, D. W. C. J. Am. Chem. Soc. 2005, 127, 8826.
6. Fonseca, M. H.; List, B. Angew. Chem. Int. Ed. 2004, 43, 3958.
7. Austin, J. F.; MacMillan, D. W. C. J. Am. Chem. Soc. 2002, 124, 1172.

OrganoCatalysts™ is a trademark of Materia, Inc.