The Total Synthesis of Racemic Teucvin and 12‐epi‐Teucvin

Abstract

Complete face‐, stereo‐, and regioselectivity in the Diels–Alder reaction of compounds 1 and 2 was the key to the first total synthesis, in racemic form, of the 19‐norclerodane diterpenoids teucvin and 12‐epi‐teucvin.

Investigating Direct Access to 2‐Oxospiro[4.5]decanones via 6π‐Electrocyclisation

“…2-oxospiro [4.5]decan-1-ones of type 4 and 8) was worthy of investigation. For example, the lactone trienes 9 and 10, via thermal or photochemical conditions, could be transformed into cyclised adducts 11 (12) and 13 (14), which then have the potential to undergo [1,5]-hydrogen shifts, affording the dienes 15 (16) and 17 (18). An additional advantage to this approach would be the relative stereocontrol of the products as described by the Woodward-Hoffmann principles [17][18][19] (Scheme 2).…”

“…Additionally, the enthalpies of the transition states for the [1,5]-shifts of the thermal cyclisation products have been calculated, to compare the activation enthalpy with experimentally determined values for unsubsituted 1,3-cyclohexadiene (∆∆H = 39.0 kcal/mol for interconversions of 2-d-1,3-cyclohexadiene; [36] similar values have been obtained for 1,4-d 2 -1,3-cyclohexadiene [37] and by calculations [38] ), which is considerably higher than that for the 6π-electrocyclisation of the unsubstituted (Z)-hexa-1,3,5-triene (∆∆H = 29.1 kcal/mol determined experimentally; [39] calculations on various levels of theory agreed with this [32] ). However, in the aromatic series 28-30, these activation enthalpies are predicted to be much smaller (23.8-24.4 kcal/mol) owing to the energetically unfavourable cyclisation products 67-69 which already possess rather high ground state energies.…”

“…Although [1,7]-hydrogen shifts are known to occur in preference to 6π-electrocyclisation [29] it is also known that subjection to high temperatures drives cyclisation, [30] however, subjecting 58 to increased temperatures failed to afford any cyclised material. To add further understanding to these results, a computational study was undertaken in which heats of formation of starting materials, the products of the electrocyclisation and the [1,5]-hydrogen shifts, and the transition states for these transformations were examined. Thus, unrestricted geometry optimisations including full frequency calculations were performed at the B3LYP/6-31g(d) level of theory.…”

“…3) are a major contributor (Figure 1). Considering the usual mode of 2-oxospiro[4.5]decan-1-one construction is to assemble the lactone portion at a later stage, [4][5][6][7][8][9][10][11][12][13][14] which often involves multiple steps, we contemplated the approach of initial γ-lactone inclusion (i.e. construction of the six-membered ring at the later stage).…”

“…Adding further to the utility of this reaction, it was found that a rearrangement of 52 could be driven at higher temperatures (Scheme 6). If the temperature was elevated to 220°C (MW) using dimethylformamide as solvent the [1,5]hydrogen shift product 56 could be obtained along with the isomeric diene 57 (1:1.5, 96 %), which was separable using silver nitrate impregnated silica gel chromatography.…”