Interrupted Baeyer–Villiger Rearrangement: Building A Stereoelectronic Trap for the Criegee Intermediate

Abstract

The instability of hydroxy peroxyesters, the elusive Criegee intermediates of the Baeyer-Villiger rearrangement, can be alleviated by selective deactivation of the stereoelectronic effects that promote the 1,2-alkyl shift. Stable cyclic Criegee intermediates constrained within a five-membered ring can be prepared by mild reduction of the respective hydroperoxy peroxyesters (β-hydroperoxy-β-peroxylactones) which were formed in high yields in reaction of β-ketoesters with BF ⋅Et O/H O .

Hyperconjugation

“…Understanding of anomeric effects in peroxides led to the recent discovery of ozone‐free synthesis of ozonides and to stereoelectronic interruption of the Baeyer–Villiger reaction that allowed the isolation of stable Criegee intermediates (vide infra) …”

“…Deeper understanding of hyperconjugative effect in transition states can be also used for raising transition state energies. Recently, selective deactivation of stereoelectronic effects was used to build a stereoelectronic trap for the Criegee intermediate of the Baeyer–Villiger rearrangement, a valuable synthetic route for converting ketones into esters …”

Domino Two‐Step Oxidation of β‐Alkoxy Alcohols to Hemiacetal Esters: Linking a Stoichiometric Step to an Organocatalytic Step with a Common Organic Oxidant

“…This preference indicates that, again, as in the case of substrates 1f and 4a , the stoichiometric BV is faster than the TEMPO‐catalyzed oxidation. Furthermore, it indicates that, in this particular case, the migration of hydroxyalkyl substituent in the Criegee intermediate is faster than that of alkoxyalkyl , . From presumed intermediate 13 two competitive pathways, one starting with the TEMPO‐catalyzed oxidation of the monoester into diglycolic anhydride ( 14 ), and another beginning with the hydrolytic opening of the monoester into transient intermediate 15 , lead to products 10 and 11 respectively.…”

C3 and C6 Modification‐Specific OYE Biotransformations of Synthetic Carvones and Sequential BVMO Chemoenzymatic Synthesis of Chiral Caprolactones

“…Conversion of 13 to 21 provides a highly efficient dual‐biocatalyst process in which a synthetic diastereopure carvone analogue(s) are the best substrate(s) for the ene‐reductase (OYE2 or PETNR) and highly effective substrate for single isomer lactone formation with CHMO. As the carvone derivatives described here contain two similar groups alpha to the carbonyl (compared to one methylene for the natural terpenoids), there are two migration pathways that may compete for any Baeyer–Villiger reaction, with O‐insertion into either C1−C2 or C1−C6 (see Scheme ). We investigated whether the substrate diastereo‐configuration would impact efficacy and regiocontrol of the subsequent BVMO reaction by evaluating both 6‐Me dihydrocarvone diastereomers 11 and 13 .…”