title: A general, enantioselective synthesis ofN-alkyl terminal aziridines and C2-functionalized azetidines via organocatalysis.
abstract: A short, high-yielding protocol involving the enantioselective α-chlorination of aldehydes has been developed for the enantioselective synthesis of C2-functionalized aziridines andN-alkyl terminal azetidines from a common intermediate. This methodology allows for the rapid preparation of functionalized aziridines in 50-73% overall yields and 88-94% ee, and azetidines in 22-32% overall yields and 84-92% ee. Moreover, we developed a scalable and cost-effective route to the key organocatalyst (54% overall yield, >95% dr).
authors.affiliation: Department of Chemistry, Vanderbitl Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37232, USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Senter
authors.affiliation: Department of Chemistry, Vanderbitl Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37232, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: O'Reilly
authors.affiliation: Department of Chemistry, Vanderbitl Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37232, USA.
authors.forename: Katherine M
authors.initials: KM
authors.lastname: Chong
authors.affiliation: Department of Chemistry, Vanderbitl Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37232, USA.
authors.forename: Gary A
authors.initials: GA
authors.lastname: Sulikowski
authors.affiliation: Department of Chemistry, Vanderbitl Institute of Chemical Biology, Vanderbilt University, Nashville, TN, 37232, USA; Department of Pharmacology, Vanderbilt Center for Neuroscience Drug Discovery, Vanderbilt University, Nashville, TN, 37232, USA.
authors.forename: Craig W
authors.initials: CW
authors.lastname: Lindsley
keywords: azetdine; aziridine; enantioselective; organocatalysis
references.citation: Chem Rev. 2003 Aug;103(8):2905-20
references.pmid: 12914485
references.citation: Chem Rev. 2014 Aug 27;114(16):7881-929
references.pmid: 24823261
references.citation: Chem Rev. 2008 Sep;108(9):3988-4035
references.pmid: 18781723
references.citation: Org Lett. 2012 Jun 1;14(11):2910-3
references.pmid: 22616979
references.citation: J Am Chem Soc. 2004 Apr 21;126(15):4790-1
references.pmid: 15080678
references.citation: Org Lett. 2010 Jul 16;12(14):3276-8
references.pmid: 20552963
references.citation: Tetrahedron Lett. 2012 Mar 28;53(13):1539-1542
references.pmid: 22919116
references.citation: J Pharm Sci. 1971 Jan;60(1):156-7
references.pmid: 5548233
references.citation: Org Lett. 2012 Feb 17;14 (4):1086-9
references.pmid: 22296172