Solid-state photochemical approaches to absolute asymmetric synthesis by irradiation of crystalline 4-alkoxy-2-pyridones
Abstract
Naturally occurring chiral $\beta$-lactams have attracted a great deal of synthetic attention because of their unique structure and interesting biological activity. The intramolecular electrophotocyclization of 4-alkoxy-2-pyridones gave the racemic-$\beta$-lactam derivatives of 5-alkoxy-3-oxo-2-azabicyclo (2.2.0) hexa-5-enes in solution in excellent yield. Refluxed in methanol, the 5-alkoxy-3-oxo-2-azabicyclo (2.2.0) hexa-5-ene is easily converted into 4-(methoxycarbonylmethyl)-azetidin-2-one in quantitative yield. The 4-(methoxycarbonylmethyl)-azetidin-2-one is a versatile synthetic intermediate for synthesis of a variety of carbapenem, penicillin and cephalosporin analogs. It is observed that most biologically active compounds are chiral molecules. However, techniques for preparing biologically active molecules in pure enantiomeric form are limited. Therefore the formation of enantiopure substances is an important chapter in the history of the evolution of stereochemistry.^ Absolute asymmetric synthesis involves the spontaneous asymmetric crystallization of achiral compounds coupled with a stereospecific solid-state phototransformation and represents a potentially simple approach to the preparation of optically enriched chiral products. To produce significant enantiomeric excesses through absolute asymmetric synthesis, the important concept is to generate chiral crystals of compounds for solid irradiation. Since the prediction of crystal structure is still unknown and the examples of achiral molecules crystallized in chiral space groups are rare and unpredictable. In this dissertation a fundamentally different kind of crystal packing controlled by steric effect was demonstrated. Eight 4-alkoxy-2-pyridone derivatives were synthesized by changing the substituent on the benzene ring. Four of them crystallized as chiral crystals. These four all are meta-disubstituted benzene species. Three of these chiral crystals led to enantiomeric excesses under solid-irradiation. In this dissertation, we provide an unusual way of controlling crystal packing, which was previously considered to be unreachable. The resulting chiral crystals are successfully applied to absolute asymmetric synthesis in receiving optically pure $\beta$-lactams. ^
Subject Area
Chemistry, Organic|Chemistry, Pharmaceutical
Recommended Citation
Lian-Chung Wu,
"Solid-state photochemical approaches to absolute asymmetric synthesis by irradiation of crystalline 4-alkoxy-2-pyridones"
(1996).
Dissertations and Master's Theses (Campus Access).
Paper AAI9702111.
http://digitalcommons.uri.edu/dissertations/AAI9702111