Iterative Pd catalyzed additions for a synthesis of methyl 7,8,11,12 tetradehydroretionate

Transition metal-catalyzed couplings of alkynes to 1,3-enynes: modern methods and synthetic applications

“…Recognizing the biological importance of both natural retinoids and their synthetic analogues, Trost and Harms targeted methyl 7,8,11,12-tetradehydroretinoate ( 219 ), an unnatural congener of retinoic acid ( 220 ) wherein the carbon framework has been rendered more rigid by the replacement of two trans -olefins with acetylenes (Scheme 33). 7c,53,54 …”

“…Recognizing the biological importance of both natural retinoids and their synthetic analogues, Trost and Harms targeted methyl 7,8,11,12-tetradehydroretinoate (219), an unnatural congener of retinoic acid (220) wherein the carbon framework has been rendered more rigid by the replacement of two trans-olefins with acetylenes (Scheme 33). 7c, 53,54 An iterative sequence of Pd-catalyzed cross couplings enabled a short and efficient synthesis of the target. In the first generation strategy, tertiary alcohol 221 was coupled with ynone 222 under standard conditions to give enyne 223, with the intention of converting the ketone moiety to a terminal alkyne via dehydration.…”

Dienolate Annulation Approach for Assembly of Densely Substituted Aromatic Architectures

“…Conjugated ester was synthesized using a a procedure modified from a previously published method; spectral data matched published spectra. Product was purified with a gradient of 20–30% EtOAc in hexanes on silica gel, giving 28 as a yellow oil as a single diastereomer according to General Procedure D (178 mg, 0.4143 mmol, 66%): 1 H NMR (500 MHz, CDCl 3 ) δ 11.34 (d, J = 10.8 Hz, 1H), 7.11 (d, J = 8.2 Hz, 2H), 6.86 (d, J = 8.2 Hz, 2H), 6.56 (d, J = 10.7 Hz, 1H), 6.31 (s, 1H), 3.90 (t, J = 7.7 Hz, 1H), 3.80 (d, J = 1.3 Hz, 3H), 2.77–2.64 (m, 2H), 1.25 (s, 9H), 0.19 (d, J = 1.4 Hz, 9H); 13 C NMR­{ 1 H} (126 MHz, CDCl 3 ) δ 22.1, 37.2, 42.2, 55.1, 57.1, 76.6, 76.9, 77.2, 103.5, 105.5, 111.5, 114.1, 129.0, 133.7, 134.0, 137.8, 145.1, 158.7, 188.5; FT-IR (NaCl Film) 2958, 2140, 1633, 1552, 1512, 1250, 1197, 1179, 1094, 1036, 843, 761 cm –1 ; HRMS (ESI + ) m / z [M + H] + calcd for C 23 H 32 NO 3 SSi, 430.1867; found, 430.1863; [α] 23 D = +12.1° ( c 1.205, CHCl 3 ).…”

“…Product was purified with a gradient of 5−15% EtOAc in hexanes on silica gel, giving 17 as a white solid and as inseparable topoisomers from General Procedure A at a maximum temperature of 50 °C (464 mg, 0.784 mmol, 73%): 1 H NMR (500 MHz, CDCl 3 ) δ 12.01 (s, 1H, topoisomer 1), 11.95 (s, 1H, topoisomer 2), 8.57 (d, J = 5.7 Hz, 2H), 7.28 (d, J = 1.7 Hz, 20H), 7.17−7.08 (m, 4H), 7.01 (dt, J = 8.3, 1.4 Hz, 2H), 6.81 (ddd, J = 9.0, 7.6, 1.5 Hz, 2H), 3.90 (s, 6H), 3.56 (s, 3H, topoisomer 1), 3.53 (s, 3H, topoisomer 2), 1.25 (s, 9H, topoisomer 1), 1.22 (s, 9H, topoisomer 2); 13 C NMR{ 1 H} (126 MHz, CDCl 3 ) δ 14.0, 22. 1, 22.2, 29.6, 55.9, 56.1, 57.8, 58.0, 60.4, 60.6, 76.6, 76.9, 77.1, 77.2, 113.5, 113.7, 113.8, 113.8, 113.9, 118.0, 118.1, 118.1, 118.4, 122.1, 122.6, 122.8, 124.2, 124.2, 124.3, 131.2, 131.3, 134.7, 134.9, 143.1, 143.2, 146.3, 146.5, 152.8, 160.5, 160.5, 164.6 ; 19 F NMR{ 1 H} (470 MHz, CDCl 3 ) δ (−63.55 topoisomer 1), (−63.54 topoisomer 2); FT-IR (NaCl) 2931, 1595, 1626, 1475, 1369, 1261.85, 1202, 1172, 1131, 1095, 977, 750, 685 (S,E)-N-((3-Hydroxy-5-methyl-[1,1′-biphenyl]-4-yl)methylene)-2-methylpropane-2-sulfinamide (18). Product was purified with a gradient of 5−15% EtOAc in hexanes on silica gel, giving 18 as a white solid from General Procedure A (48.9 mg, 0.1550 mmol, 82%): 1 H NMR (500 MHz, CDCl 3 ) δ 11.78 (s, 1H), 9.07 (s, 1H), 7.63−7.59 (m, 2H), 7.46−7.42 (m, 2H), 7.41−7.35 (m, 1H), 7.10 (d, J = 1.7 Hz, 1H), 7.01 (dd, J = 1.8, 0.9 Hz, 1H), 2.61 (s, 3H), 1.28 (s, 9H); 13 C NMR{ 1 H} (125 MHz, CDCl 3 ) δ 162.…”

The first palladium-catalyzed 1,4-addition of terminal alkynes to conjugated enones

“…10 Furthermore, although palladium is one of the most used metals from the periodic table in catalysis, palladium-catalyzed conjugated addition of alkynes to enones has not been reported to the best of our knowledge. 11 We hypothesized that the failure could be attributed to (1) either the facile homo-or heterodimerization of terminal alkynes (a well-known, synthetically useful process) 12 to form by-products or (2) a lower reactivity of the alkynyl palladium intermediate towards enones. Conceivably, such obstacles can be overcome by tuning the electronic properties of the ligands to coordinate with palladium.…”