Synthesis and structure–activity relationship of dihydrobenzofuran derivatives as novel human GPR119 agonists

Catalytic diastereo- and enantioselective additions of versatile allyl groups to N–H ketimines

“…Oxidative cleavage of the vinyl group, reduction of the resulting aldehyde and subjection of the resulting primary alcohol to triflic anhydride (−20 °C, 2 h) 25 delivered 13 in 75% yield after recrystallization (this compound is unstable towards a variety of chromatography procedures). The aryl ring in 13 may be functionalized site selectively according to formerly reported procedures 42,43,44 (see the Supplementary Information for extended bibliography). …”

Application of Electrochemical Processes to Classical Iodocyclisation: Utility for Selectivity and Mechanistic Insight

“…93–95 °C (lit. : 89–90 °C); 1 H NMR (400 MHz, CDCl 3 ) δ=7.87–7.82 ( m , 2H, Ar H ), 6.85–6.82 ( m , 1H, Ar H ), 6.07‐5.95 ( m , 1H, C H =), 5.49 ( broad s , 1H, O H ), 5.22–5.14 ( m , 2H, =C H 2 ), 3.88 ( s , 3H, C H 3 ), 3.44 ( dt , J =6.3, 1.7 Hz, 2H, C H 2 ) ppm; Data in agreement with literature …”

“…Iodocyclisation of alkenes with oxygen nucleophiles is a powerful method of generating furan and benzofuran frameworks that maintain the iodine functionality and thereby allow further manipulation . The benzofuran motif is an important framework in a variety of natural products and drug substances and as such, rapid and efficient processes for the construction of substituted variants via the construction of the bicyclic nucleus are synthetically valuable . With our own research interests in practical electrochemical processes we here report an efficient route for the construction of the dihydrobenzofuran framework through an iodoetherification reaction of 2‐allylphenols where the molecular iodine and a Lewis acid are electrochemically generated from benign starting materials.…”

“…[1][2][3][4][5] The benzofuran motif is an important framework in a variety of natural products and drug substances and as such, rapid and efficient processes for the construction of substituted variants via the construction of the bicyclic nucleus are synthetically valuable. [6][7][8][9][10][11][12][13] With our own research interests in practical electrochemical processes we here report an efficient route for the construction of the dihydrobenzofuran framework through an iodoetherification reaction of 2-allylphenols where the molecular iodine and a Lewis acid are electrochemically generated from benign starting materials. Examples of iodocyclisation of phenols onto alkenes are conspicuously sparse in the literature with only a few examples being noted.…”

Design and synthesis of 1H-pyrazolo[3,4-c]pyridine derivatives as a novel structural class of potent GPR119 agonists

“…Therefore, we first pursued a highly potent GPR119 agonist, assuming that the orientation of the methylsulfonylphenyl group and piperidine carbamate group would have an impact on the agonist potency, and we designed compounds focusing on conformationally restricted central spacers as the first step. [15][16][17][18] Evaluation of the designed spacers was conducted based on a ligand-based pharmacophore model.…”