Proton transfers in the Strecker reaction revealed by DFT calculations

• Published in: Beilstein Journal of Organic Chemistry Vol. 10; no. 1; pp. 1765 - 1774
• Main Authors: Yamabe, Shinichi, Zeng, Guixiang, Guan, Wei, Sakaki, Shigeyoshi
• Format: Journal Article
• Language: English
• Published: Germany Beilstein Institut 01.08.2014; Beilstein-Institut
• Subjects: amide intermediate; Chemistry; DFT calculations; Full Research Paper; hydrogen bonds; Organic chemistry; Q; QD241-441; Science; Strecker reaction; transition state; transition state; Strecker reaction; amide intermediate; hydrogen bonds; DFT calculations
• ISSN: 1860-5397; 1860-5397
• DOI: 10.3762/bjoc.10.184

The Strecker reaction of acetaldehyde, NH 3 , and HCN to afford alanine was studied by DFT calculations for the first time, which involves two reaction stages. In the first reaction stage, the aminonitrile was formed. The rate-determining step is the deprotonation of the NH 3 + group in MeCH(OH)-NH 3 + to form 1-aminoethanol, which occurs with an activation energy barrier (Δ E ≠ ) of 9.6 kcal/mol. The stereochemistry ( R or S ) of the aminonitrile product is determined at the NH 3 addition step to the carbonyl carbon of the aldehyde. While the addition of CN − to the carbon atom of the protonated imine 7 appears to scramble the stereochemistry, the water cluster above the imine plane reinforces the CN − to attack the imine group below the plane. The enforcement hinders the scrambling. In the second stage, the aminonitrile transforms to alanine, where an amide Me-CH(NH 2 )-C(=O)-NH 2 is the key intermediate. The rate-determining step is the hydrolysis of the cyano group of N(amino)-protonated aminonitrile which occurs with an Δ E ≠ value of 34.7 kcal/mol. In the Strecker reaction, the proton transfer along the hydrogen bonds plays a crucial role.