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. 2020 Aug 19;142(33):14286-14294.
doi: 10.1021/jacs.0c05917. Epub 2020 Aug 4.

Regiodivergent Hydroborative Ring Opening of Epoxides via Selective C-O Bond Activation

Marc Magre  1 , Eva Paffenholz  1 , Bholanath Maity  2 , Luigi Cavallo  2 , Magnus Rueping  2
Affiliations

Regiodivergent Hydroborative Ring Opening of Epoxides via Selective C-O Bond Activation

Marc Magre et al. J Am Chem Soc. .

Abstract

A magnesium-catalyzed regiodivergent C-O bond cleavage protocol is presented. Readily available magnesium catalysts achieve the selective hydroboration of a wide range of epoxides and oxetanes yielding secondary and tertiary alcohols in excellent yields and regioselectivities. Experimental mechanistic investigations and DFT calculations provide insight into the unexpected regiodivergence and explain the different mechanisms of the C-O bond activation and product formation.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Scheme 1
Scheme 1. Catalytic Methods for the Regioselective Ring Opening of Epoxides
Scheme 2
Scheme 2. Scope of the MgBu2-Catalyzed Hydroboration of Epoxides and Oxetanes
1a–1aj (1 mmol), HBpin (1.5 equiv), MgBu2 (5 mol %, 0.5 M in heptane), THF [0.5 M], 40 °C for 24 h. Isolated yields. Toluene [1 M], 10 mol % MgBu2, 90 °C. Enantioselectivities were determined by HPLC. Diastereoselectivities were determined by 1H NMR. (R)- and (S)-1m, (S)-1n, and (R)- and (S)-1o epoxides were used in 99% ee purity. (R)-1n epoxide was used in 97% ee purity (all isolated from preparative HPLC; for more information, see Supporting Information). Epoxides 1w, 1x, 1y, 1z, and 1aa were diasteriomerically pure. MgBu2 (5 mol %, 0.5 M in heptane), toluene [1 M], 75 °C for 24 h.
Scheme 3
Scheme 3. Regiodivergent Magnesium-Catalyzed Hydroboration of Epoxides
Scheme 4
Scheme 4. Mg(NTf2)2-Catalyzed Hydroboration of Epoxides
1 (1 mmol), Mg(NTf2)2 (5 mol %), HBpin (1.5 equiv) in THF [0.5 M] at 40 °C for 24 h. Mg(NTf2)2 (10 mol %).
Scheme 5
Scheme 5. Control Experiments
Figure 1
Figure 1
Computed energy profile for the ring-opening step in MgBu2-catalyzed hydroboration of the epoxide reaction. Free energy values at M06-2X(SMD, THF solvent)/Def2-TZVPP//PBE0/Def2-SVP level of theory are presented.
Figure 2
Figure 2
Computed energy profile for the metathesis of Mg–O and B–H bonds in MgBu2-catalyzed hydroboration of the epoxide reaction. For energy convention refer to Figure 1.
Figure 3
Figure 3
Steric map of the epoxide-coordinated intermediate A7h. The percentage of buried volume is reported near each of the quadrants. For clarity, the 3D geometry of the coordinated epoxide is overlapped on the steric map. The scale of the steric contours is also reported. The middle point of the epoxide C–C bond is placed at the origin, and the epoxide O atom is placed on the Z-axis.
Figure 4
Figure 4
Computed energy profile for the Mg(NTf2)2-catalyzed ring-opening hydroboration of epoxide. For energy convention refer to Figure 1.
Scheme 6
Scheme 6. Energetics for the Step of Racemization of Mg(NTf2)2-Catalyzed Reaction
See this image and copyright information in PMC

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