Organic Chemistry Portal
Organic Chemistry Highlights

Monday, July 19, 2010
Douglass F. Taber
University of Delaware

Enantioselective Construction of Alkylated Stereogenic Centers

Xiang-Ping Hu and Zhuo Zheng of the Dalian Institute of Chemical Physics developed (Org. Lett. 2009, 11, 3226, DOI: 10.1021/ol9012469; J. Org. Chem. 2009, 74, 9191, DOI: 10.1021/jo901619c) a family of Rh catalysts for the enantioselective hydrogenation of allylic phosphonates such as 1. Hon Wai Lam of the University of Edinburgh established (J. Am. Chem. Soc. 2009, 131, 10386. DOI: 10.1021/ja904365h) that alkenyl heterocycles such as 3 could be reduced with high ee. The product 4 could be hydrolyzed to the carboxylic acid, although that transformation was not reported by the authors.

Ken Tanaka of the Tokyo University of Agriculture and Technology showed (J. Am. Chem. Soc. 2009, 131, 12552. DOI: 10.1021/ja905908z) that an isopropenyl amide 6 could be hydroacylated with high ee. Gregory C. Fu of MIT observed (J. Am. Chem. Soc. 2009, 131, 14231. DOI: 10.1021/ja9061823) that nitromethane 9 could be added to the allenyl amide 8 to give 10, the product of γ-bond formation. Robert K. Boeckman, Jr. of the University of Rochester devised (Org. Lett. 2009, 11, 4544. DOI: 10.1021/ol9017479) what appears to be a general protocol for the construction of alkylated ternary and quaternary centers, enantioselective hydroxymethylation of an aldehyde 11.

In another approach to the construction of alkylated quaternary centers, Varinder K. Aggarwal of the University of Bristol demonstrated (Angew. Chem. Int. Ed. 2009, 48, 6289. DOI: 10.1002/anie.200901900) that an enantiomerically-enriched trifluoroborate salt 14 could be added to an aromatic aldehyde 15 with retention of absolute configuration. The salt 14 was prepared from the corresponding high ee secondary benzyl alcohol.

Weinreb amides are versatile precursors to a variety of functional groups. Stephen G. Davies of the University of Oxford devised (Org. Lett. 2009, 11, 3254. DOI: 10.1021/ol901174t) a chiral Weinreb amide equivalent 17 that could be alkylated with high de. The minor diastereomer from the alkylation was readily separable by silica gel chromatography. Keiji Maruoka of Kyoto University established (Angew. Chem. Int. Ed. 2009, 48, 5014. DOI: 10.1002/anie.200901977) that a chiral phase transfer catalyst was effective for the enantioselective alkylation of the alkynyl ester 19.

Emmanuel Riguet of the Université de Reims Champagne-Ardenne developed (Tetrahedron Lett. 2009, 50, 4283. DOI: 10.1016/j.tetlet.2009.05.011) an improved catalyst for the enantioselective addition of malonate 22 to cyclohexenone 21. Diego A. Alonso and Carmen Nájera of the Universidad de Alicante devised (J. Org. Chem. 2009, 74, 6163. DOI: 10.1021/jo9010552) an organocatalyst for the addition of methyl acetoacetate 25 to a nitroalkene 24. José Luis García Ruano and José Alemán of the Universidad Autónoma de Madrid observed (Chem. Commun. 2009, 4435. DOI: 10.1039/b908963b) that an organocatalyst could also direct the enantioselective conjugate addition of the bis sulfone 28 to an unsaturated aldehyde 27. As the sulfone can be completely desulfurized, either before or after alkylation, the net transformation is the conjugate addition of an alkyl group.

Takahiro Nishimura and Tamio Hayashi, also of Kyoto University, reported (Angew. Chem. Int. Ed. 2009, 48, 8057. DOI: 10.1002/anie.200904486) a chiral Rh catalyst for the enantioselective conjugate addition of the TIPS-acetylene 31 to an unsaturated aldehyde. Karl Anker Jřrgensen of Aarhus University described (J. Am. Chem. Soc. 2009, 131, 10581. DOI: 10.1021/ja903920j) a complementary approach, the enantioselective addition of a sulfonyl ketone 34. The adduct 35 could be processed into the alkyne 36, or into the alkene (not shown).

D. F. Taber, Org. Chem. Highlights 2010, July 19.