Formation of Complex α-Imino Esters via Multihetero-Cope Rearrangement of α-Keto Ester Derived NitronesThe project described was supported by Award R35 GM118055 from the National Institute of General Medical Sciences. K.M.K. was supported in part through the Matthew Neely Jackson Undergraduate Research Fellowship (UNC).
Received: 23 October 2018
Accepted: 30 October 2018
06 December 2018 (online)
This work was carried out in the Department of Chemistry at UNC Chapel Hill, which celebrated its bicentennial in 2018.
Published as part of the 50 Years SYNTHESIS – Golden Anniversary Issue
A sequential benzoylation and multihetero-Cope rearrangement of α-keto ester derived nitrones has been developed. The reaction furnishes a diverse array of complex α-imino ester derivatives. The products can be transformed into amino alcohols via LiAlH4 reduction.
- 1 Current address: Enanta Pharmaceuticals, 500 Arsenal Street, Watertown, MA 02472, USA.
- 2 Current address: Elder Research, 14 E Peace St., Suite 302, Raleigh, NC 27604, USA.
- 3 Tabolin AA, Ioffe SL. Chem. Rev. 2014; 114: 5426
- 4 Cummins CH, Coates RM. J. Org. Chem. 1983; 48: 2070
- 5 Beshara CS, Hall A, Jenkins RL, Jones KL, Jones TC, Killeen NM, Taylor PH, Thomas SP, Tomkinson NC. O. Org. Lett. 2005; 7: 5729
- 6 Malinowski JT, Malow EJ, Johnson JS. Chem. Commun. 2012; 48: 7568
- 7 Steward KM, Johnson JS. Org. Lett. 2011; 13: 2426
- 8 Zavesky BP, Bartlett SL. Org. Lett. 2017; 19: 2126
- 9 Esteves CH. A, Koyioni M, Christensen KE, Smith PD, Donohoe TJ. Org. Lett. 2018; 20: 4048
- 10 For the decomposition of 3k (Scheme 4) via a mechanism reminiscent of serine and threonine dehydratases, see: Grabowski R, Hofmeister AE. M, Buckel W. Trends Biochem. Sci. 1993; 18: 297
- 11 Nakamura A, Lectard S, Hashizume D, Hamashima Y, Sodeoka M. J. Am. Chem. Soc. 2010; 132: 4036
- 12 Pfeiffer JY, Beauchemin AM. J. Org. Chem. 2009; 74: 8381