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. 2019 Feb 6;141(5):1903-1907.
doi: 10.1021/jacs.8b13403. Epub 2019 Jan 24.

Sequential Functionalization of meta-C-H and ipso-C-O Bonds of Phenols

Jiancong Xu  1 , Jingjing Chen  1 , Feng Gao  1 , Shuguang Xie  1 , Xiaohua Xu  1   2 , Zhong Jin  1   2 , Jin-Quan Yu  3
Affiliations

Sequential Functionalization of meta-C-H and ipso-C-O Bonds of Phenols

Jiancong Xu et al. J Am Chem Soc. .

Abstract

The use of a template as a linchpin motif in directed remote C-H functionalization is a versatile yet relatively underexplored strategy. We have developed a template-directed approach to realizing one-pot sequential palladium-catalyzed meta-selective C-H olefination of phenols, and nickel-catalyzed ipso-C-O activation and arylation. Thus, this bifunctional template converts phenols to synthetically useful 1,3-disubstituted arenes.

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Conflict of interest statement

The authors declare no competing financial interests.

Figures

Figure 1.
Figure 1.
Development of new bifunctional templates for sequential meta-C–H/ipso-C–O functionalization of phenols.
Scheme 1.
Scheme 1.. Design of New Template for meta-C-H Olefination of Phenola
aYield and regioselectivity were determined by 1H NMR with CH2Br2 as an internal standard. bReaction time: 36 h.
Scheme 2.
Scheme 2.
Recovery and Regeneration of Template
Scheme 3.
Scheme 3.. Application to Synthesis of the Central Scaffold of Natural Antibiotic TMC-95a
aConditions: (1) T1 (1 eq), KOH (1 eq), THF, rt, 95%. (2) olefin (3 eq), Pd(OAc)2 (10 mol%), Ac-Gly-OH (20 mol%), AgOAc (1.5 eq), HFIP (0.2 M), 80 °C, 36 h, 68%. (3) morpholine (1 eq), dioxane, 100 °C, 12 h, 99%. (4) Tf2O (1.1 eq), Pyridine (2.5 eq), CH2Cl2, 0 °C to rt, 3 h, 75%. (5) B2(pin)2 (2 eq), Pd(OAc)2 (10 mol%), DPEphos (20 mol%), TEA (4 eq), dioxane, 80 °C, 16 h, 90 %. (6) ArBr 8 (1.1 eq), Pd(dppf)Cl2 (20 mol%), K2CO3 (4 eq), DME, 80 °C, 14 h, 92%. (7) ArBpin 9 (4 eq), Ni(xantphos)Cl2 (10 mol%), K3PO4 (7 eq), toluene, 120 °C, 24 h, 18%.
See this image and copyright information in PMC

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