Intramolecular [4 + 4] photocycloaddition of 2-pyridones tethered by a three-carbon chain: studies on the formation of cycloadducts and control of stereogenesis. 3

Abstract

Irradiation of a pair of 2-pyridones tethered at the 3-and 6'-positions by a three-carbon chain initiates an efficient [4 + 4] cycloaddition to produce a densely functionalized, fused 5-8 carbocyclic ring system with the trans isomer predominant. An asymmetric center on the tether influences stereogenesis at the four new tetrahedral centers. This effect was probed with an alcohol substituent and its silyl ether as a function of solvent. A combination of interand intramolecular hydrogen-bonding can account for the observed levels of selectivity. Some of the cis products are unstable and undergo Cope rearrangement, yielding cyclobutane isomers.The clinical efficacy of taxol* 12 and the reticence of its tetracyclic ring system to yield to total synthesis3 has brought eight-membered ring construction and manipulation to the forefront of the synthetic chemistry agenda.4 Recent disclosures of new cyclooctane-containing natural products combining novel architecture and biological activity are further stimulation for this area of research.5 * Dedicated to Professor G. C. Taylor on the occasion of his 70th birthday.

Further Studies on the [1,2]-Wittig Rearrangement of 2-(2-Benzyloxy)aryloxazolines

“…Following a literature procedure [ 21 ], 2-chloronicotinic acid 20 (5.51 g, 35.0 mmol) was added in small portions to a stirred 0 °C suspension of sodium hydride (60% in mineral oil, 3.87 g, 96.8 mmol) in DMF (55 cm 3 ). After stirring at 0 °C for 30 min, benzyl alcohol (4.19 g, 38.7 mmol) was added and the reaction mixture was heated at 75 °C for 18 h. After cooling to rt, the reaction mixture was poured into 1 M HCl (140 cm 3 ) and extracted with Et 2 O (4 × 75 cm 3 ).…”

“…The crude residue was recrystallised (EtOAc) to give 21 (6.52 g, 81%) as colourless crystals; mp 132–135 °C; (lit. [ 21 ] 134.5–136 °C); δ H (500 MHz) 10.67 (1 H, br s, CO 2 H), 8.49 (1 H, dd, J 7.5, 2.0, ArH), 8.41 (1 H, dd, J 4.8, 2.0, ArH), 7.48 (2 H, d, J 7.0, Ph), 7.44–7.37 (3 H, m, Ph), 7.15 (1 H, dd, J 7.5, 4.8, ArH) and 5.64 (2 H, s, CH 2 ). The 1 H NMR spectral data were in accordance with those previously reported [ 21 ].…”

“…A literature procedure [ 21 ] was adapted as follows: 1,1′-Carbonyldiimidazole (2.94 g, 18.1 mmol) was added to a stirred suspension of 2-(benzyloxy)nicotinic acid 21 (4.16 g, 18.1 mmol) in CH 2 Cl 2 (20 cm 3 ). After stirring at rt for 15 min, the resultant solution was added to a solution of 2-amino-2-methylpropan-1-ol (1.79 g, 20.1 mmol) in CH 2 Cl 2 (10 cm 3 ) and the reaction mixture was stirred at rt for 18 h before being diluted with Et 2 O (75 cm 3 ) and washed with 0.25 M HCl (2 × 50 cm 3 ).…”

Fusicoccin Synthesis by Intramolecular [4+4] Photocycloaddition of 2-Pyridones: Stereocontrol of the Cycloaddition and Elaboration of the Pentacyclic Product

“…Increasing the polarity of the solvent from benzene (E T =34.3) 19 to chlorobenzene (E T =36. 8) and trifluoromethylbenzene (E T =38.5) decreases the cis selectivity to 95% and 80%, respectively. Use of dichloromethane (E t =40.7) yields mostly the trans-isomer (25% cis).…”

Fusicoccin Ring System by [4 + 4] Cycloaddition. Control of Diastereoselectivity through Hydrogen Bonding

“…During the cycloaddition, two stereogenic centers (C-3 and C-12) should cooperatively influence stereogenesis at C-11 . Control of the stereogenic center C-7 would optimally be addressed by a cis-selective cycloaddition to give 2 . The trans -8,9-diol would be derived via epoxidation of the disubstituted alkene.…”