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. 2021 Jun 30;143(25):9343-9349.
doi: 10.1021/jacs.1c05212. Epub 2021 Jun 21.

Enantioselective Iridium-Catalyzed Allylation of Nitroalkanes: Entry to β-Stereogenic α-Quaternary Primary Amines

Woo-Ok Jung  1 , Binh Khanh Mai  2 , Brian J Spinello  1 , Zachary J Dubey  1 , Seung Wook Kim  1 , Craig E Stivala  3 , Jason R Zbieg  3 , Peng Liu  2 , Michael J Krische  1
Affiliations

Enantioselective Iridium-Catalyzed Allylation of Nitroalkanes: Entry to β-Stereogenic α-Quaternary Primary Amines

Woo-Ok Jung et al. J Am Chem Soc. .

Abstract

The first systematic study of simple nitronate nucleophiles in iridium-catalyzed allylic alkylation is described. Using a tol-BINAP-modified π-allyliridium C,O-benzoate catalyst, α,α-disubstituted nitronates substitute racemic branched alkyl-substituted allylic acetates, thus providing entry to β-stereogenic α-quaternary primary amines. DFT calculations reveal early transition states that render the reaction less sensitive to steric effects and distinct trans-effects of diastereomeric chiral-at-iridium π-allyl complexes that facilitate formation of congested tertiary-quaternary C-C bonds.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
Unactivated nitronates in catalytic enantioselective allylic alkylations of mono-substituted π-allyl precursors.
Figure 2.
Figure 2.
Computed activation free energies of the addition of −CMe2NO2 to different π-crotyliridium(III) isomers. All activation barriers (ΔG‡) are with respect to A_endo_distal.
Figure 3.
Figure 3.
Origin of regioselectivity. Bisphosphine ligand and some H-atoms are omitted for clarity. All Gibbs free energies are in kcal/mol with respect to A_endo_distal. ΔEdist-Ir: distortion energy of the π-crotyliridium complex to reach its geometry in the TS for nucleophilic addition.
Figure 4.
Figure 4.
Electronic effects on allylation regioselecitivy of different stereoisomers of the π-crotyliridium complex.
Figure 5.
Figure 5.
Optimized structures for additions of −CMe2NO2 anion giving branched product. Gibbs free energies are with respect to A_endo_distal.
Scheme 1.
Scheme 1.
Iridium-catalyzed allylation nitroalkanes 2a-2j using allylic acetates 1a-1n to form homoallylic nitroalkanes 3a-3x.a aYields are of material isolated by silica gel chromatography. Enantioselectivities were determined by chiral stationary phase HPLC analysis. bNMP was used as the reaction solvent. c(S)-Ir-tol-BINAP, X= OMe. dIr-catalyst (10 mol%). See Supporting Information for experimental details.
Scheme 2.
Scheme 2.
Zinc-mediated reduction of 3f, 3k, 3l, 3s and 3v to form β-stereogenic α-quaternary primary amines 4f, 4k, 4l, 4s and 4v. aYields are of material isolated after filtration through celite. See Supporting Information for experimental details
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