title: Stereoselective synthesis of cis- or trans-3,5-disubstituted pyrazolidines via Pd-catalyzed carboamination reactions: use of allylic strain to control product stereochemistry through N-substituent manipulation.
abstract: The stereoselective synthesis of either trans- or cis-3,5-disubstituted pyrazolidines is accomplished via Pd-catalyzed carboamination reactions of unsaturated hydrazine derivatives. The products are obtained in good yield with up to >20:1 diastereoselectivity. Stereocontrol is achieved by modulating the degree of allylic strain in the transition state for syn-aminopalladation through a simple modification of the substrate N(2)-substituent. The pyrazolidine products can be further transformed to 3,5-disubstituted pyrazolines via deprotection/oxidation, or to substituted 1,3-diamines via N-N bond cleavage.
authors.affiliation: Department of Chemistry, University of Michigan, 930 North University Avenue, Ann Arbor, Michigan 48109-1055, USA.
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Giampietro
authors.forename: John P
authors.initials: JP
authors.lastname: Wolfe
mesh_terms: D000498:Allyl Compounds / Q000737:chemistry*; D000586:Amination; D002384:Catalysis; D006834:Hydrazines / Q000737:chemistry; D010165:Palladium / Q000737:chemistry; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D000498:Allyl Compounds; D006834:Hydrazines; D011720:Pyrazoles; D010165:Palladium
references.citation: European J Org Chem. 2007 Feb;2007(4):571-582
references.pmid: 20577649
references.citation: Angew Chem Int Ed Engl. 2007;46(41):7789-92
references.pmid: 17876796
references.citation: J Org Chem. 2005 Apr 15;70(8):3099-107
references.pmid: 15822970
references.citation: Bioorg Med Chem Lett. 2007 Nov 1;17(21):5897-901
references.pmid: 17827004
references.citation: J Am Chem Soc. 2005 Jul 20;127(28):9974-5
references.pmid: 16011341
references.citation: Curr Opin Drug Discov Devel. 2004 Jul;7(4):498-506
references.pmid: 15338959
references.citation: J Am Chem Soc. 2004 Sep 15;126(36):11279-82
references.pmid: 15355109
references.citation: Org Lett. 2008 Jun 19;10(12):2377-9
references.pmid: 18503279
references.citation: J Org Chem. 2008 Jan 18;73(2):550-7
references.pmid: 18085795
references.citation: Bioorg Med Chem Lett. 2005 Mar 1;15(5):1337-40
references.pmid: 15713382
references.citation: Angew Chem Int Ed Engl. 2004 Jul 5;43(27):3605-8
references.pmid: 15293259
references.citation: Bioorg Med Chem. 2003 Nov 3;11(22):4815-25
references.pmid: 14556798
references.citation: J Am Chem Soc. 2004 Feb 18;126(6):1620-1
references.pmid: 14871078
references.citation: Org Lett. 2006 May 25;8(11):2213-6
references.pmid: 16706489
references.citation: Bioorg Med Chem Lett. 2006 Apr 15;16(8):2256-9
references.pmid: 16455247
references.citation: Org Lett. 2000 Dec 28;2(26):4265-7
references.pmid: 11150215
references.citation: Org Lett. 2005 Sep 29;7(20):4487-9
references.pmid: 16178565
references.citation: J Org Chem. 2005 Dec 9;70(25):10368-74
references.pmid: 16323846
references.citation: Bioorg Med Chem. 2007 Mar 1;15(5):1896-902
references.pmid: 17251028
references.citation: Chemistry. 2007;13(33):9310-6
references.pmid: 17696188
references.citation: Tetrahedron. 2008;64(29):6838-6852
references.pmid: 19122758
references.citation: Org Lett. 2004 Feb 19;6(4):637-40
references.pmid: 14961642
references.citation: Angew Chem Int Ed Engl. 2006 Oct 27;45(42):7079-82
references.pmid: 17009380