Yamada clutch

The Yamada coupling (also Yamada reaction ) is a name reaction in organic chemistry , which was named after Shun-ichi Yamada and was first introduced in 1973. It is a condensation reaction in which a carboxylic acid and an amine react with one another to form an amide or peptide . Diethyl cyanophosphonate is used as the coupling reagent .

Overview reaction

A carboxylic acid and an amine react after activation by diethyl cyanophosphonate (DEPC) in the presence of a tertiary amine, here triethylamine , to form an amide or peptide. Mostly dimethylformamide (DMF) or dichloromethane (CH ₂ Cl ₂ ) are used as solvents .

Reaction mechanism

It is believed that by the attack of triethylamine 1 to the carboxylic acid 2 , a carboxylate - anion is formed. This attacks the phosphorus atom of diethyl cyanophosphonate 3 . When the cyanide anion is split off , an activated carboxylic acid phosphate ester 4 is formed . The nucleophilic addition of the amine 5 to the compound 4 forms the compound 6 , from which the amide 7 is ultimately obtained.

Sample reaction

The Yamada coupling enables, among other things, the synthesis of a large number of different amides. The amide 3 below could be obtained, for example, from 2- (2-hydroxyethoxy) acetic acid 1 and the amine 2 with the coupling reagent DECP in the presence of triethylamine in DMF with a yield of 90%.

application

The Yamada coupling is particularly useful for peptide synthesis . One advantage of the Yamada coupling is that there is no racemization of individual amino acid building blocks. This allows the reaction with the DECP coupling reagent to be used for the production of drugs such as antibiotics .

Individual evidence

↑ Shun-ichi Yamada, Yutaka Kasai, Takayuki Shioiri: Diethylphosphoryl cyanide. A new reagent for the synthesis of amides. In: Tetrahedron Letters . tape 14 , no. 18 . Great Britiain 1973, p. 1595-1598 .
↑ ^a ^b ^c Zerong Wang: Yamada Coupling . In: Comprehensive Organic Name Reactions and Reagents . John Wiley & Sons, Inc., Hoboken, NJ, USA 2010, ISBN 978-0-470-63885-9 , pp. 3105-3108 , doi : 10.1002 / 9780470638859.conrr687 .
↑ ^a ^b ^c ^d Jie Jack Li, EJ Corey: Name Reactions for Functional Group Transformations . John Wiley & Sons, Inc., Hoboken, New Jersey 2007, ISBN 978-0-470-17651-1 , pp. 500-502 , doi : 10.1002 / 9780470176511 .

[1] Shun-ichi Yamada, Yutaka Kasai, Takayuki Shioiri: Diethylphosphoryl cyanide. A new reagent for the synthesis of amides. In: Tetrahedron Letters . tape 14 , no. 18 . Great Britiain 1973, p. 1595-1598 .

[:0-2] Zerong Wang: Yamada Coupling . In: Comprehensive Organic Name Reactions and Reagents . John Wiley & Sons, Inc., Hoboken, NJ, USA 2010, ISBN 978-0-470-63885-9 , pp. 3105-3108 , doi : 10.1002 / 9780470638859.conrr687 .

[:1-3] Jie Jack Li, EJ Corey: Name Reactions for Functional Group Transformations . John Wiley & Sons, Inc., Hoboken, New Jersey 2007, ISBN 978-0-470-17651-1 , pp. 500-502 , doi : 10.1002 / 9780470176511 .