Fig. 2: Synthesis and crystallographic analysis of 2-oxabicyclo[2.1.1]hexanes.
From: 2-Oxabicyclo[2.1.1]hexanes as saturated bioisosteres of the ortho-substituted phenyl ring
a, Gram-scale synthesis of compound 1b. THF, tetrahydrofuran; quant., quantitative. b, X-ray crystal structures of compounds 5b and 9b. Hydrogen atoms are omitted for clarity. Carbon, grey; oxygen, red; fluorine, green. c, Definition of vectors n1 and n2, and geometric parameters d, r, φ1, φ2 and θ. Ortho-substituted phenyl ring and 2-oxabicyclo[2.1.1]hexane are shown as examples. d, Geometric parameters d, r, φ1, φ2 and |θ| for ortho-substituted benzenes (valsartan, telmisartan), the saturated literature bioisosteres 25–27 and water-soluble saturated bioisosteres 5b and 9b. aData is taken from ref. 67. bData is taken from ref. 68. cData is taken from ref. 54. dData is taken from ref. 55.
