Diterpenoid total synthesis, an A .fwdarw. B .fwdarw. C approach. 9. Structure and stereochemistry of tricyclic intermediates

Abstract

Michael addition of the sodium enolate of a tert-butyl 0-keto ester to a 4,4,10-trisubstituted 8-formyl-A8-7-octalone (2)2 was shown earlier to afford adducts of general structure 3 which upon exposure to acid undergo tert-butyl ester cleavage, decarboxylation, and cyclodehydration to produce tricyclic enediones 6 or 8. Spectroscopic evidence, primarily NMR, is presented to demonstrate that the double bond in these enediones is normally in the 13,14 position (6) rather than the 8,14 position (8) when C-13 carries fewer than two substituents, and that the relative configuration of the carbon skeleton is trans-syn-cis in 6 and by inference trans-syn in 8. Intramolecular ketals 20 and 22, in which the C-10-C-9-C-8 configuration can only be anti-cis or syn-cis, were synthesized from enedione 6g by routes which do not alter the configuration at these sites. Relation of ketal 20 to saturated diketone 17, which must be either trans-anti-trans or trans-syn-cis because it does not epimerize in base, confirms the trans-syn-cis configuration of these substances. Stereoselectivity in the Michael addition producing adducts 3 therefore leads exclusively to the 9a orientation of the /5-keto ester side chain. In cases where more than one stereoisomeric adduct 3 is formed, it is shown that the configurational difference is only at C-ll.

Mn(III)-Mediated Radical Cyclization for Δ1-3-Octalone Synthesis

“…5 This tandem sequence has been successfully applied to acyclic α,β-unsaturated carbonyl compounds for the efficient synthesis of conjugated cyclohexenones. 6 The success of the above cyclization method lies on the fact that base-catalyzed conjugate addition of the activated methylene unit to acyclic α,β-unsaturated carbonyl compounds proceeds rapidly.…”

Diterpenoid total synthesis, an A .fwdarw. B .fwdarw. C approach. 11. C-ring deoxy aromatic systems. Total synthesis of methyl (.+-.)-dehydroabietate

“…Methyl 12-Hydr oxy-7-oxo-5a-abieta-8,11,13-trien-l 5-oate (4). A mixture of 550 mg (1.60 mmol) of chromatographed 2 and 610 mg (1.91 mmol) of pyridine hydrobromide perbromide, mp 132-135 °C, in 50 mL of HOAc was stirred for 35 min (N2 atmosphere) and subjected to isolation C (CHCI3; 5% NaHCOa wash) to afford a mixture of 3 and 4 as a tan solid: NMR 2.12 (s, 1 H), 3.23 (s, 1 ), 5.02 (d, J = 12.5 Hz, 1 ), 8.51 (s, 3 H), plus resonances of 4 (below). A solution of this mixture in 100 mL of HOAc containing 2 g of Zn dust was stirred at 45 °C for 4 h,11 filtered, and subjected to isolation C (CHCI3; 5% NaHCOs wash) to provide 450 mg (82%) of 4 as a colorless solid, mp 220-230 °C.…”

“…Methyl 12-(2'-Benzoxazolyloxy)-7-oxo-5a-abieta-8,11,13trien-l 5-oate (5). According to a general procedure of Musliner and Gates9 a mixture of 139 mg (0.400 mmol) of 4, mp 234-236 °C, 68 mg (0.44 mmol) of 2-chlorobenzoxazole, and 250 mg of anhydrous K2COs in 20 mL of dry Me2CO was stirred under reflux for 18 h (dry atmosphere), solvent was removed in vacuo, and the residue was partitioned between CHCI3 and water.…”