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Article

Synthesis of Tetra-ortho-substituted, Phosphorus-Containing and Carbonyl-Containing Biaryls Utilizing a Diels−Alder Approach

Supporting Info

Bradley O. Ashburn, Rich G. Carter,* and Lev N. Zakharov^†

Contribution from the Department of Chemistry, 153 Gilbert Hall, Oregon State University, Corvallis, Oregon 97331

J. Am. Chem. Soc., 2007, 129 (29), pp 9109–9116

DOI: 10.1021/ja071163r

Publication Date (Web): June 29, 2007

In papers with more than one author, the asterisk indicates the name of the author to whom inquiries about the paper should be addressed.

†

Director of X-ray Crystallographic Facility, Department of Chemistry, Oregon State University, Corvallis, Oregon 97331 and Department of Chemistry, University of Oregon, Eugene, Oregon 97403. E-mail: lev@ uoregon.edu.

, rich.carter@oregonstate.edu

Abstract

The application of the Diels−Alder approach to biaryls (DAB) is described for the synthesis of tetra-ortho-substituted biaryl compounds containing orthogonally functionalized substituents. The syntheses of phosphorus-containing, disubstituted alkynes and carbonyl-containing, disubstituted alkynes were accomplished in two to three steps from commercially available reagents. Subsequent Diels−Alder cycloadditions with a range of oxygenated dienes yielded the target biaryls. Further functionalization through palladium-couplings is demonstrated on the phosphorus-containing biaryls. In addition, selective manipulation of each of the remaining ortho substituents on the phosphorus-containing biaryls is demonstrated. One of these phosphorus-containing derivatives is utilized as a highly active catalyst for Suzuki coupling. For the carbonyl-containing series, a wide range of dienophile substituents were screened including esters, ketones, and amides. The key Diels−Alder cycloadditions proceeded smoothly with the commercially available 1-methoxy-1,3-cyclohexadiene to yield the resultant tetra-ortho-substituted biaryls with excellent regioselectivity. The scope of the cycloaddition process was also explored on the carbonyl-containing dienophiles with a series of cyclic dienes. Acyclic dienes were also screened; however, they did not prove effective in the Diels−Alder process with the carbonyl-containing acetylenes. The ability to isolate enantiomerically pure biaryl atropisomers using a benzyl oxazolidinone is disclosed. Finally, the subsequent conversion to an axially chiral anilino alcohol is also reported.

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