Reactions via Hydrogen-Bonded Associates

Enantioselective addition of hydrogen cyanide to aldehydes, discovered by Bredig and Fiske in 1912 (21), is probably one of the earliest 

ASYMMETRIC CATALYSIS WITH PURELY ORGANIC COMPOUNDS 

SCHEME 10. Asymmetric ring opening of cyclic anhydrides. 

Asymmetric polymerization of prochiral monomers, if feasible, would be an important class of synthetic reactions. The first trial was reported by Marvel who, in 1943, attempted asymmetric vinyl polymerization of styrene, methyl methacrylate, and acrylonitrile by using optically active acyl peroxides (32). All attempts, however, were unsuccessful. 

---

Reactions via Covalently Bound Intermediates / 323 Reactions via Hydrogen-Bonded Associates / 328... 

The hydration number (the number of water molecules intimately associated with the salt) of the quaternary ammonium salt is very dependent upon the anion. The change in the order of reactivity is thus believed to be due to the hydration of the anion the highly hydrated chloride and cyanide ions are less reactive than expected, and the poorly hydrated iodide fares better under phase transfer conditions than in homogeneous reactions. Methanol may specifically solvate the anions via hydrogen bonding, and this effect is responsible for the low reactivity of more polar nucleophiles in that solvent. 

Outside of the enzyme we are limited to two molecule collisions, because the odds of a simultaneous collision of three independent molecules in the proper orientation for reaction are very slim. Three molecule collisions are considered a mechanistic possibility only when two of the three reacting molecules are loosely associated via hydrogen bonding or pi-complexation. However, within the enzyme s active site, there can be several groups snuggled around our reactant to contribute as needed to lower the reaction barrier by stabilizing the transition state. 

Recent interest in the use of N-unsubstituted 2-quinolones stems from the fact, that they coordinate effectively to chiral lactam-based templates via two hydrogen bonds. The prototypical template to be used in photochemical reactions is compound 115, which can be readily prepared from Kemp s triacid [108]. The template is transparent at a wavelength X > 290 nm, and can be nicely used in stoichiometric amounts for enantioselective photochemical and radical reactions [109]. Conditions which favor hydrogen bonding (nonpolar solvent, low temperature) are required to achieve an efficient association of a given substrate. The intramolecular [2 + 2]-photocycloaddition of 4-alkylquinolone 114 proceeded in the presence of 115 with excellent enantioselectivity, and delivered product 116 as the exclusive stereoisomer (Scheme 6.41) [110]. Application of the enantiomer ent-115 ofcomplexing agent 115 to the reaction 111 —> 112 depicted in Scheme 6.40 enabled enantioselective access to (+ )-meloscine [111]. 

---