Diversity Oriented Approach to Polycyclic Compounds through the Diels–Alder Reaction and the Suzuki Coupling

Abstract

A diversity oriented strategy has been demonstrated to deliver small “drug like” molecules using alkylation, Diels–Alder reaction, and Suzuki–Miyaura cross‐coupling as key steps. This methodology allows access a wide range of molecules using simple scaffolds such as indanes, tetralins and tetrahydroisoquinolines, which can enhance the chemical space for potential therapeutic molecules.

Diversity oriented approach to polycyclics via cross-enyne metathesis and Diels–Alder reaction as key steps

“…Recently, Kotha and Seema reported a preliminary communication involving the application of cross-enyne metathesis (CEM) and the DA reaction as key steps for assembling the biaryl derivatives. 9 Herein, we report the full details about the preparation of biaryls and two amino acid derivatives as additional examples. 10 Table 1.…”

“…126.1, 128.3, 128.7, 131.8, 133.0, 137.5, 140.0, 141.8, 159.8, 166.5, 169.8 4, 52.8, 94.3, 115.8, 126.4, 128.97, 129.1, 132.1, 134.2, 137.4, 138.3, 139.0, 140.4, 141.2, 166.3, 169.7 ppm. 4, 52.8, 94.3, 115.8, 126.4, 128.9, 129.1, 132.1, 134.2, 137.4, 138.3, 139.0, 140.4 14.1, 21.7, 32.8, 35.3, 39.0, 52.7, 56.6, 62.3, 115.7, 127.2, 128.2, 128.9, 134.1, 135.2, 136.5, 136.5, 136.7, 137.4 4,4a,9,9a,: 1 H NMR (400 MHz, CDCl 3 ): δ1.28 (s, 9H), 1.4-1.6 (m, 6H), 1.6-2.2 (m, 9H), 3.7-3.9 (m, 1H), 4.1-4.2 (m, 1H), 4.35-4.45 (m, 1H), 4.9-5.1 (m, 2H), 5.76-5.80 (m, 2H), 7.7-7.9 (m, 2H), 8.1-8.3 (m, 2H) ppm. : R f = 0.85 (silica gel, 5% EtOAc/petroleum ether).…”

“…IR (Neat) ν max : 740, 1266, 1497, 1731, 2954 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ): δ 3.93 (s, 3H), 3.94 (s, 3H), 7.44 (dd, J 1 = 6.8, J 2 = 2.0 Hz, 3H), 7.54 dd, J 1 = 6.8, J 2 = 2.0 Hz, 2H), 7.70 (dd, J 1 = 8, J 2 = 2.0 Hz, 1H), 7.85 (dd, J 1 = 8.0, J 2 = 1.6 Hz, 1H) ppm; 13 C NMR (100 MHz, CDCl 3 ): δ 52.8, 52. 9,127.3,127.4,128.6,129.4,130.3,133.3,134.9,137.5,143.2,167.6,: R f = 0.38 (silica gel, EtOAc/petroleum ether). IR (Neat) ν max : 743, 819, 1265, 1734, 2852 cm −1 ; 1 H NMR (400 MHz, CDCl 3 ): δ 3.92 (s, 3H), 3.94 (s, 3H), 7.45 (d, J = 2.4 Hz, 2H), 7.60 (d, J = 1.6 Hz, 2H), 7.70 (dd, J 1 = 8, J 2 = 1.8 Hz, 1H), 7.85 (dd, J 1 = 9.2, J 2 = 2 Hz, 2H) ppm; 13 C NMR (100 MHz, CDCl 3 ): δ 52.8, 52.…”

Design and synthesis of fused polycycles via Diels–Alder reaction and ring-rearrangement metathesis as key steps

“…Our strategy to polycycles involves a Diels–Alder reaction (DA) [ 23 – 25 ], a Grignard addition [ 26 ] and a RRM as key steps. To begin with, a double DA reaction of cyclopentadiene ( 1 ) with 1,4-benzoquinone ( 2 ) gave the known bis-adduct 3 [ 27 – 28 ].…”

Development of New Synthetic Strategies, Tactics and their Applications

“…To this end, benzyl dibromides 328 a – c were treated separately with DEAM to deliver the corresponding Tic derivatives 329 a – c . Next, the resulting halogen containing Tic derivatives 329 a – c were functionalized with the aid of SM coupling (Scheme ) …”