A Highly Diastereoselective Dioxetane Formation by the Hydroxy-Directed [2+2] Cycloaddition of Singlet Oxygen to a Chiral Allylic Alcohol

Abstract

Chiral auxiliaries have been successfully employed in controlling the diastereoselectivity of numerous reactions. 1 A notoriously difficult problem is the manipulation of the stereochemical course of singlet oxygen ( 1 O 2 ), the smallest possible cyclophile. In the past few years, we have shown that through the appropriate choice of the chiral inductor it is possible to control the stereoselectivity of the [4 + 2] cycloaddition of 1 O 2 . 2 For this purpose, optically active 2,2-dimethyloxazolidines proved to be highly effective chiral auxiliaries when attached to sorbic acid in the form of an amide linkage. Recently we have also discovered the diastereoselective ene reaction of 1 O 2 with optically active oxazolidines, which have been equipped with an urea functionality. 3 The diastereoselective control was achieved in this ene reaction through remote hydrogen bonding between the urea NH bond and 1 O 2 , whereas steric factors were held responsible in the [4 + 2] cycloaddition. Similar efficacious hydrogen-bonding effects have been documented 4 for the [2 + 2] cycloadditions of 1 O 2 with chiral allylic alcohols. To date, no cases appear to be known in which steric interactions efficiently guide the π-facial attack of 1 O 2 in the dioxetane formation; however, the stereoselective dioxetane formation in the ozonolysis of vinylsilanes has been reported. 5 Herein we report the first example of a chiral-auxiliary-induced [2 + 2] cycloaddition between 1 O 2 and oxazolidinone-functionalized enecarbamates, which proceeds with complete diastereoselectivity as a result of steric repulsions.Evans' chiral auxiliary 6 was introduced into the enecarbamate substrate 2 by condensing the 4-alkyl-substituted oxazolidinones with the aldehyde

Synthesis of 1,2‐Dioxetanes as Thermochemiluminescent Labels for Ultrasensitive Bioassays: Rational Prediction of Olefin Photooxygenation Outcome by Using a Chemometric Approach

“…It is known that the formal [2+2] cycloaddition of singlet oxygen to alkenes takes place efficiently on electron‐rich systems . However, the mechanism of this process has been extensively debated in the literature (Scheme ), and the most reliable one can vary case by case, depending on the molecular structure of the substrate,,–, the solvation energy,,, and also the sensitizer employed ,,,. As a consequence, the nature of the olefin substituents (electron‐donating ability, presence of hydrogen‐bond acceptors and/or donors, geometry, and steric hindrance) not only affects the success of singlet oxygen addition, but it also determines the reaction pathway.…”

A Mechanistic Spectrum of Chemical Reactions

“…The steering effect of the hydrogen bonding was applied to a highly diastereoselective dioxetane formation from a chiral allylic alcohol (Scheme 21) [110]. …”

Stereocontrolled Photooxygenations–A Valuable Synthetic Tool§

“…The parallelism of the stereochemical results in all three reaction modes of lo2 makes a hydrogen-bonded intermediate very likely for diastereomeric control (30,31). This intermediate is thought to be an exciplex in all cases, i.e.…”

“…Recently, also the hydroxy-group-directed diastereoselectivity has been tested in the [2+2] cycloaddition mode by using the adamantylidene-substituted chiral allylic alcohol 16 (30). As shown in Table 5 , the rhreo-17 dioxetane was only formed in the photooxygenation of 16 in CDCl,, whereas the diastereoselectivity drops in the more polar methanol/ CCI4 mixture.…”