Catalytic Enantioselective α-Tosyloxylation of Ketones Using Iodoaryloxazoline Catalysts: Insights on the Stereoinduction Process

Abstract

A family of iodooxazoline catalysts was developed to promote the iodine(III)-mediated α-tosyloxylation of ketone derivatives. The α-tosyloxy ketones produced are polyvalent chiral synthons. Through this study, we have unearthed a unique mode of stereoinduction from the chiral oxazoline moiety, where the stereogenic center alpha to the oxazoline oxygen atom is significant. Computational chemistry was used to rationalize the stereoinduction process. The catalysts presented promote currently among the best levels of activity and selectivity for this transformation. Evaluation of the scope of the reaction is presented.

Evolution of N‐Heterocycle‐Substituted Iodoarenes (NHIAs) to Efficient Organocatalysts in Iodine(I/III)‐Mediated Oxidative Transformations

“…Based on this so-called "hypervalent twist", chiral iodoarene pre-catalysts were designed employing an ortho-oxazoline moiety, with the p-chloro derivative 2 being the most efficient. [25,26] A similar reactivity enhancing effect was observed for the o-Me-substituted iodoarene catalyst 3 by Whitehead and co-workers. [27] Furthermore, this was also observed for aryl-λ 3 -iodanes such as for pseudocyclic benziodoxole tosylates 4 introduced by Zhdankin and co-workers.…”

“…This dramatically enhances reactivity by accelerating further ligand exchange processes and favoring the final reductive collapse of the iodine(III) into its monovalent iodine(I) state within the final oxidative coupling step. Based on this so‐called “hypervalent twist”, chiral iodoarene pre‐catalysts were designed employing an ortho ‐oxazoline moiety, with the p ‐chloro derivative 2 being the most efficient . A similar reactivity enhancing effect was observed for the o ‐Me‐substituted iodoarene catalyst 3 by Whitehead and co‐workers .…”

N‐Heterocycle‐Stabilized Iodanes: From Structure to Reactivity

“…Based on these advantages, it is surprising that pseudocyclic N‐heterocycle‐stabilized iodanes (NHIs) have been only rarely described (Figure B). In recent examples, chiral oxazoline‐ and pyridine‐modified aryl iodides as well as the oxidized λ 3 ‐ and λ 5 ‐iodanes have been described by Birmann, Legault, and Wirth . Even though these heterocyclic substitutions lead to enhanced reactivities and stereoselectivities in oxidative transformations, a direct interaction of the nitrogen atom with the hypervalent iodine center could not be ascertained.…”

“…In recent examples, chiral oxazoline-and pyridine-modified aryl iodides as well as the oxidized l 3 -a nd l 5 -iodanes have been described by Birmann, Legault, and Wirth. [21,[24][25][26][27][28] Even thought heseh eterocyclic substitutions lead to enhanced reactivities and stereoselectivities in oxidative transformations, ad irect interaction of the nitrogen atom with the hypervalent iodine center could not be ascertained. (2-Pyridinyl)-substituted aryl-l 3 -iodane 7,d iscovered by MuÇiz and co-workers, was the first example in which ad irectN ÀIi nteraction wasc onfirmed using X-ray structurea nalysis for an N-heterocyclic substituent.…”

Chiral Hypervalent Iodine Reagents: Synthesis and Reactivity

“…Almost simultaneously, Legault et al 42a. reported a new pre‐catalyst iodoarene 98 bearing a chiral oxazoline ring moiety, using for its synthesis the experimental procedure developed by Birman et al.…”