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. 2008 Oct 1;130(39):12907-11.
doi: 10.1021/ja8050487. Epub 2008 Sep 6.

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

Natalie C Giampietro  1 , John P Wolfe
Affiliations

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

Natalie C Giampietro et al. J Am Chem Soc. .

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.

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Figures

Scheme 1
Scheme 1
2,5-Disubstituted Heterocycle Stereochemistry
Scheme 2
Scheme 2
Transition States for Pyrazolidine Synthesis
Scheme 3
Scheme 3
Syn-1,3-Diamine Synthesis
Scheme 4
Scheme 4
Anti-1,3-Diamine Synthesis
Scheme 5
Scheme 5
Synthesis of 3,5-Disubstituted Pyrazolines
See this image and copyright information in PMC

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