Jocic reaction explained

In organic chemistry, the Jocic reaction, also called the Jocic–Reeve reaction (named after Zivojin Jocic[1] and Wilkins Reeve[2]) is a name reaction that generates α-substituted carboxylic acids from trichloromethylcarbinols and corresponding nucleophiles in the presence of sodium hydroxide. The reaction involves nucleophilic displacement of the hydroxyl group in a 1,1,1-trichloro-2-hydroxyalkyl structure with concomitant conversion of the trichloromethyl portion to a carboxylic acid or other acyl group.

The key stages of the reaction involve an SN2 reaction, where the nucleophile displaces the oxygen with geometric inversion.

Mechanism

The reaction mechanism involves an epoxide intermediate that undergoes an SN2 reaction by the nucleophile. As a result of this mechanistic aspect, the reaction can easily occur on secondary or tertiary positions, and chiral products can be made by using chiral alcohol substrates.[3] [4] The reaction is one stage of the Corey–Link reaction, the Bargellini reaction, and other processes for synthesizing α-amino acids and related structures. Using hydride as the nucleophile, which also reduces the carbonyl of the product, allows this sequence to be used as a homologation reaction for primary alcohols.[5]

Scope

Examples of this reaction include:
Generation of α-azidocarboxylic acids with the use of sodium azide as the nucleophile in DME with the presence of sodium hydroxide.[6]
Conversion of aldehydes to homoelongated carboxylic acids, by first reacting with trichloromethide to form a trichloromethylcarbinol, then undergoing a Jocic reaction with either sodium borohydride or sodium phenylseleno(triethoxy)borate as the nucleophile in sodium hydroxide.[7] This reaction can be followed by the introduction of an amine, to form the corresponding homoelongated amides.[8]

Notes and References

  1. Jocic . Zivojin . Zhurnal Russkago Fiziko-Khimicheskago Obshchestva (Journal of the Russian Physical-Chemical Society) . 1897 . 29 . 97.
  2. Reeve . Wilkins . McKee . James R. . Brown . Robert . Lakshmanan . Sitarama . McKee . Gertrude A. . Studies on the rearrangement of (trichloromethyl)carbinols to α-chloroacetic acids . Canadian Journal of Chemistry . 1 March 1980 . 58 . 5 . 485–493 . 10.1139/v80-078. free .
  3. Synthesis . 1971 . 131–138 . 10.1055/s-1971-21677 . Reactions of Aryl Trichloromethyl Carbinols with Nucleophiles . Wilkins . Reeve . 1971 . 3 .
  4. Practical Approach to α- or γ-Heterosubstituted Enoic Acids . Julia L. . Shamshina . Timothy S. . Snowden . Org. Lett. . 2006 . 8 . 25 . 5881–5884 . 10.1021/ol0625132 . 17134296 .
  5. European Journal of Organic Chemistry . One‐Carbon Homologation of Primary Alcohols and the Reductive Homologation of Aldehydes Involving a Jocic‐Type Reaction . Zhexi . Li . Manoj K. . Gupta . Timothy S. . Snowden . 2015 . 2015 . 32 . 7009–7019 . 10.1002/ejoc.201501089 .
  6. Corey. Elias James. Link. John O.. 1 February 1992. A general, catalytic, and enantioselective synthesis of α-amino acids. Journal of the American Chemical Society. 114. 5. 1906–1908. 10.1021/ja00031a069.
  7. Cafiero. Lauren R.. Snowden. Timothy S.. 8 August 2008. General and Practical Conversion of Aldehydes to Homologated Carboxylic Acids. Organic Letters. 10. 17. 3853–3856. 10.1021/ol8016484. 18686964.
  8. Gupta. Manoj K.. Li. Zhexi. Snowden. Timothy S.. 5 March 2014. Preparation of One-Carbon Homologated Amides from Aldehydes or Primary Alcohols. Organic Letters. 16. 6. 1602–1605. 10.1021/ol500200n. 24593196.