Practical Organocatalytic Synthesis of Functionalized Non‐C2‐Symmetrical Atropisomeric Biaryls |
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| Authors: | Dr. Hongyin Gao Prof. Dr. Qing‐Long Xu Craig Keene Dr. Muhammed Yousufuddin Prof. Dr. Daniel H. Ess Prof. Dr. László Kürti |
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| Affiliation: | 1. Department of Chemistry, Rice University, BioScience Research Collaborative, 6500 Main Street, Rm 380, Houston, TX 77030 (USA);2. Current address: Jiangsu Key Laboratory of Drug Discovery for Metabolic Disease and State Key Laboratory of Natural Medicines China Pharmaceutical University, 24 Tongjia Xiang, Nanjing 210009 (P.R. China);3. Life and Health Sciences Department, The University of North Texas at Dallas, Dallas, TX 75241 (USA);4. Department of Chemistry and Biochemistry, Brigham Young University, Provo, UT 84602 (USA) |
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| Abstract: | An organic acid catalyzed direct arylation of aromatic C(sp2)? H bonds in phenols and naphthols for the preparation of 1,1′‐linked functionalized biaryls was developed. The products are non‐C2‐symmetrical, atropoisomeric, and represent previously untapped chemical space. Overall this transformation is operationally simple, does not require an external oxidant, is readily scaled up (up to 98 mmol), and the structurally diverse 2,2′‐dihydroxy biaryl (i.e., BINOL‐type), as well as 2‐amino‐2′‐hydroxy products (i.e., NOBIN‐type) are formed with complete regioselectivity. Density‐functional calculations suggest that the quinone and imino‐quinone monoacetal coupling partners are exclusively arylated at their α‐position by an asynchronous [3,3]‐sigmatropic rearrangement of a mixed acetal species which is formed in situ under the reaction conditions. |
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| Keywords: | atropisomerism biaryls organocatalysis rearrangements synthetic methods |
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