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Synfacts 2014; 10(2): 0111
DOI: 10.1055/s-0033-1340505
Synthesis of Natural Products and Potential Drugs
© Georg Thieme Verlag Stuttgart · New York

Synthesis of (S)-Sitagliptin

Contributor(s):
Philip Kocienski
Bao H, Bayeh L, Tambar UK * The University of Texas Southwestern Medical Center at Dallas, USA
Catalytic Enantioselective Allylic Amination of Olefins for the Synthesis of ent-Sitagliptin.

Synlett 2013;
24: 2459-2463
Article in Thieme ConnectGoogle Scholar
Further Information

Publication History

Publication Date:
20 January 2014 (online)

 
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Key words

sitagliptin - dipeptidyl dipeptidase-4 inhibitor - asymmetric allylic amination - palladium - ene reaction - [2,3]-sigmatropic rearrangement

Significance

Sitagliptin is a dipeptidyl dipeptidase-4 inhibitor that is prescribed for the treatment of type II diabetes. The small-scale synthesis depicted features a two-step construction of the allylic amine E involving an ene reaction using the sulfurdiimide B followed by a palladium-catalyzed asymmetric [2,3]-sigmatropic rearrangement of ylid C.


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Comment

The ylid C does not undergo a [2,3]-sigmatropic rearrangement at 4 °C in the absence of the palladium catalyst. A further five 4-arylbut-1-ene substrates with F, CF3 and OMe substituents gave the allylic amination products in 79–94% yield and 81–94% ee.


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