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. 2020 Sep 16;142(37):16090-16096.
doi: 10.1021/jacs.0c08150. Epub 2020 Sep 3.

Enantioselective Aryl-Iodide-Catalyzed Wagner-Meerwein Rearrangements

Hayden A Sharma  1 , Katrina M Mennie  1 , Eugene E Kwan  1 , Eric N Jacobsen  1
Affiliations

Enantioselective Aryl-Iodide-Catalyzed Wagner-Meerwein Rearrangements

Hayden A Sharma et al. J Am Chem Soc. .

Abstract

We report a strategy for effecting catalytic, enantioselective carbocationic rearrangements through the intermediacy of alkyl iodanes as stereodefined carbocation equivalents. Asymmetric Wagner-Meerwein rearrangements of β-substituted styrenes are catalyzed by the C2-symmetric aryl iodide 1 to provide access to enantioenriched 1,3-difluorinated molecules possessing interesting and well-defined conformational properties. Hammett and kinetic isotope effect studies, in combination with computational investigations, reveal that two different mechanisms are operative in these rearrangement reactions, with the pathway depending on the identity of the migrating group. In reactions involving alkyl-group migration, intermolecular fluoride attack is product- and enantio-determining. In contrast, reactions in which aryl rearrangement occurs proceed through an enantiodetermining intramolecular 1,2-migration prior to fluorination. The fact that both pathways are promoted by the same chiral aryl iodide catalyst with high enantioselectivity provides a compelling illustration of generality across reaction mechanisms in asymmetric catalysis.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
A) Stereospecific cationic rearrangements. B) Successful examples of enantioselective, catalytic rearrangements involve semipinacol rearrangements of allylic alcohol derivatives. C) Aryl iodide-catalyzed enantioselective fluorofunctionalizations. D) Aryl iodide-promoted Wagner–Meerwein rearrangements (this work). E) Mechanistic considerations. LG = leaving group. G = potential migrating group. Ar = aryl.
Figure 2.
Figure 2.
A) Substrate scope for the enantioselective, catalytic Wagner-Meerwein rearrangements. Reactions were carried out using 0.52 mmol scale of styrenyl substrate 2, catalyst 1 (20 mol%), mCPBA (0.57 mmol), and pyr·9HF (10.4 mmol HF) in DCM (3.0 mL). a100 equiv HF were employed. Conditions for step a: 4e (0.45 mmol), KOTMS (0.9 mmol) in Et2O (2.7 mL) and THF (1.8 mL). B) Oxidative degradation of 3e to carboxylic acid 7. Conditions: B) product 2c (0.25 mmol), RuCl3·(H2O)3 (2.5 μmol), and NaIO4 (3.49 mmol) in H2O (1.3 mL), MeCN (0.65 mL), and CCl4 (0.65 mL) at room temperature for 18 h C) Azidation of the tertiary fluoride 4a. Conditions: 4a (0.185 mmol), TMSN3 (0.37 mmol), and B(C5F5)3 (9 μmol) in MeNO2 (93 μL) at room temperature for 90 min. All yields are of isolated products.
Figure 3.
Figure 3.
General mechanistic considerations in I(III)-promoted oxidative difunctionalizations of alkenes
Figure 4.
Figure 4.
A) Aryl-rearrangement mechanistic possibilities. B) Hammett study of the aryl migration revealing that the aryl migration step is the first substrate-committing step and therefore enantiodetermining.
Figure 5.
Figure 5.
A) Alkyl-rearrangement mechanistic possibilities. B) 12C/13C KIE experiments.
Scheme 1.
Scheme 1.
Proposed catalytic cycles based on Hammett, KIE, and computational analyses.
See this image and copyright information in PMC

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