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. 2011 May 11;133(18):6956-9.
doi: 10.1021/ja202007s. Epub 2011 Apr 20.

Ligand steric contours to understand the effects of N-heterocyclic carbene ligands on the reversal of regioselectivity in Ni-catalyzed reductive couplings of alkynes and aldehydes

Peng Liu  1 , John Montgomery, K N Houk
Affiliations

Ligand steric contours to understand the effects of N-heterocyclic carbene ligands on the reversal of regioselectivity in Ni-catalyzed reductive couplings of alkynes and aldehydes

Peng Liu et al. J Am Chem Soc. .

Abstract

The regioselectivities of N-heterocyclic carbene (NHC) ligands in Ni-catalyzed alkyne-aldehyde reductive coupling reactions with silane reducing agents are investigated using density functional theory. Reversal of regioselectivity can be achieved by varying the steric bulkiness of the ligand. The steric influences of NHC ligands are highly anisotropic. Regioselectivity is primarily controlled by the steric hindrance at the region of the ligand close to the alkyne. Analysis of 2D contour maps of the NHC ligands indicates that the regioselectivities are directly affected by the shape and orientation of the N-substituents on the ligand.

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Figures

Figure 1
Figure 1
Oxidative addition transition states with ligand 5a.
Figure 2
Figure 2
Oxidative addition transition states with ligand 5d.
Figure 3
Figure 3
The CPK model and 2D contour maps of the van der Waals surface of ligands 5a, 5c, and 5d. Distances are in Å. Ni is located at the origin of the coordinate system in the contour maps and is shown in green in the CPK models. Contour line of zero is defined as in the same plane of the Ni atom. Negative distance (red) indicates the ligand is closer to substrate; positive distance (blue) indicates the ligand is further away from substrate. The position of the distal alkyne substituent is marked with “X”. The region of the ortho, meta, and para substituents on ligand 5d is marked with “o”, “m”, and “p”, respectively.
Scheme 1
Scheme 1
Ni-catalyzed reductive alkyne–aldehyde couplings of alkynes and aldehydes with N-heterocyclic carbene (NHC) ligands.
See this image and copyright information in PMC

References

    1. Hoveyda AH, Evans DA, Fu GC. J Am Chem Soc. 1993;93:1307.
    2. Miller KM, Jamison TF. J Am Chem Soc. 2004;126:15342. - PubMed
    3. Bahadoor AB, Flyer A, Micalizio GC. J Am Chem Soc. 2005;127:3694. - PubMed
    4. Reichard HA, McLaughlin M, Chen MZ, Micalizio GC. Eur J Org Chem. 2010:391. - PMC - PubMed
    5. Liu P, Sirois LE, Cheong PHY, Yu ZX, Hartung IV, Rieck H, Wender PA, Houk KN. J Am Chem Soc. 2010;132:10127–10135. - PubMed

    1. This strategy is exemplified by the acid-catalyzed hydration of olefins compared with hydroboration-oxidation protocols.

    1. Hein JE, Fokin VV. Chem Soc Rev. 2010;39:1302. - PMC - PubMed
    2. Boren BC, Narayan S, Rasmussen LK, Zhang L, Zhao HT, Lin ZY, Jia GC, Fokin VV. J Am Chem Soc. 2008;130:8923. - PubMed
    1. Ohmura T, Oshima K, Taniguchi H, Suginome M. J Am Chem Soc. 2010;132:12194. - PubMed
    1. Malik HA, Sormunen GJ, Montgomery J. J Am Chem Soc. 2010;132:6304. - PMC - PubMed

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