Desymmetrization Explained

Desymmetrization is a chemical reaction that converts prochiral substrates into chiral products. Desymmetrisations are so pervasive that they are rarely described as such except when they proceed enantioselectively. The enantioselective reactions require chiral catalysts or chiral reagents.[1] According to IUPAC]], desymmetrization involves the "... the conversion of a prochiral molecular entity into a chiral one."[2]

Examples

Typical substrates are epoxides, diols, dienes, and cyclic carboxylic acid anhydrides.[1]

One example is the conversion of cis-3,5-diacetoxycyclopentene to monoacetate. This particular conversion utilizes the enzyme cholinesterase.[3]

In another example, a symmetrical cyclic imide is subjected to asymmetric deprotonation resulting in a chiral product with high enantioselectivity.[4]

Partial hydrogenation]] converts benzil (PhC(O)C(O)Ph) into chiral hydrobenzoin. The process can be implemented enantioselectively using transfer hydrogenation.

(Ph = The precursor benzil has C2v symmetry, and the product is C2 symmetric.

Citric acid is also a symmetric molecule that can be desymmetrized by partial methylation.

The alcoholysis of cyclic anhydrides can be conducted enantiosymmetrically using chiral amine catalysts.[5]

A related example is the hydrolysis of prochiral diesters catalyzed by chiral phosphoric acids.[6]

Formal symmetry considerations

Desymmetrizations involve the loss of an improper axis of rotation (mirror plane, center of inversion, rotation-reflection axis). In other words, desymmetrisations convert prochiral precursors into chiral products.[7]

Notes and References

  1. Willis, Michael C. "Enantioselective desymmetrization" Journal of the Chemical Society, Perkin Transactions 1: Organic and Bio-Organic Chemistry 1999, pp. 1765-1784.
  2. desymmetrization . IUPAC Gold Book. 2014 . 10.1351/goldbook.D01623 . free .
  3. Donald R. Deardorff, Colin Q. Windham, and Chris L. Craney "Enantioselective Hydrolysis of cis-3,5-diacetoxycyclopentene: (1R,4S)-(+)-4-Hydroxy-2-cyclopentenyl Acetate" Organic Syntheses, Coll. Vol. 9, p.487 (1998); Vol. 73, p.25 (1996).
  4. Vincent Rodeschini, Nigel S. Simpkins, and Fengzhi Zhang "Chiral lithium amide base desymmetrization of a ring fused imide: formation of (3as,7as)-2-[2-(3,4-dimethoxyphenyl)-ethyl]-1,3-dioxo-octahydro-isoindole-3a-carboxylic acid methyl ester" Org. Synth. 2007, volume 84, 306.
  5. 10.15227/orgsyn.082.0120 . Asymmetric Alcoholysis of Meso-Anhydrides Mediated by Alkaloids . Organic Syntheses . 2005 . 82 . 120. Carsten. Bolm. Iuliana. Atodiresei. Ingo. Schiffers .
  6. 10.15227/orgsyn.093.0075 . Enantioselective Synthesis of α,α-Disubstituted Lactones via a Chiral Brønsted Acid Catalyzed Intramolecular Cyclization . 2016 . Wilent . Jennifer . Qabaja . G. . Petersen . K. S. . Organic Syntheses . 93 . 75–87 . 28042185 . 5198840 .
  7. Basic Terminology of Stereochemistry, G.P. Moss Ed. Pure Appl. Chem., Vol. 68, No. 12, pp. 2193-2222, 1996.