Regioselectivity in the reactions of methoxydehydrobenzenes with furans. Part 3. 3-Methoxyfuran and methoxydehydrobenzenes and the chemistry of their adducts

Abstract

The cycloadditions of met hoxydehydrobenzenes containing a 3met hoxy group and 3met hoxyfuran are highly regioselective. The adducts, 1,4-dihydro-2-methoxy-1,4-epoxynaphthalenes, undergo mild acid-catalysed hydrolysis providing, first, an isolable 1,2,3,4-tetrahydro-2-methoxy-1,4-epoxynaphthalen-2-01, and then a 3,4-dihydro-l,4-epoxynaphthalen-2(1 H ) -o n e . The chemistry of these ketones is explored. One of them, 3,4-dihydro-5-methoxy-l,4-epoxynaphthalen-2( 1 H ) -one, readily undergoes catalytic reduction t o yield the hexahydro-l,4-epoxynaphthalene-2,5( 1 H,4aH)dione. The X-ray molecular structure of this dione and of the 2-monobrosyl ester of the derived diol are reported. Treatment of the above adducts with trifluoroacetic acid and acetic anhydride provides a convenient synthesis of 1 -acetoxy-2-methoxynaphthalenes.14 could be isolated by fractional crystallization of the crude epoxynaphthalen-2(1H)-one 23 (Scheme 4) (1-H, 6, 5.29 and product. The structural assignment of the hemiacetal 14 is 4-H, 8, 5.88). Therefore the 5-methoxy ketone 15 is that based on its spectral data. The IR spectrum exhibited a band at ketone in which 1-H resonates at 6, 5.01 and 4-H at 6, 5.89. 3370 cm-' attributed to an OH stretching frequency. The ''C and the 8-methoxy ketone 16 is the one in which 1-H resonates NMR spectrum revealed a signal for the methoxy group of the at 6, 5.24 and 4-H at 6, 5.69. in their respective ' H NMR hemiacetal at 6, 50.06, a quaternary carbon atom attributed to spectra. Similar assignments allow distinctions to be made C-2 resonating at 6, 106.39, and the methylene carbon signal between the pairs of ketones 31/32 (Scheme 5), 38/39 (Scheme 6) at 6, 43.02 was attributed to C-3. Nuclear Overhauser effect and 52153 (Scheme 8). (NOE) difference spectroscopy gave evidence for the stereochemistry and the results are shown in Fig. I . Significant interactions are those between the endo-methoxy group at C-2 and both the bridgehead proton 1-H and 3-H,,d,, and between 3-H,,, and the eso-hydroxy group at C-2. Nucleophilic attack by water therefore occurs exclusively from the e.uo-face of the adduct and this mode of attack presumably reflects the unhindered nature of this face of the molecule compared with the endo-face. The spectroscopic properties of the hemiacetal 4 derived from the parent adduct 2 are similar to those of the methoxy derivative 14. In this case the infrared O H stretching 23 9% 19 5% n 39 7% 9 3%* See under section 5.6.

Remote Electronic Effects in the Rhodium-Catalyzed Nucleophilic Ring Opening of Oxabenzonorbornadienes

“…Remote electronic effects mediated by an aromatic π-system have been thoroughly investigated for the transformation of substituted oxabenzonorbornadienes to the corresponding naphthols under protic conditions . In two typical examples, treatment of oxabenzonorbornadienes 1 and 3 under acidic conditions gave one of two possible regioisomeric naphthol products ( 2 and 4 ) exclusively, since in both cases the depicted carbocationic intermediate is strongly favored by conjugative stabilization (Scheme ) .…”

Preparation of 2-Substituted 3-Methoxycarbonyl-4-methoxyfurans that Allow Access to Highly Functionalized Naphthalenes via Regioselective Cycloaddition with Alkoxybenzyne

“…13c,f,g,i,14 Given the case, a prototype of the present case is Sargent's report on the reaction of α-methoxybenzyne (X) with β-methoxyfuran (XI), where the cycloaddition mode shown in Figure 2 (B) is favored (selectivity 86:14). 6 Considering the polarization of furan XI by electron donation from the methoxy group, this outcome could be rationalized by the HOMO-LUMO interaction as shown in Figure 2 (B). Turning attention to the present case, furan 5 could be regarded as a derivative of β-methoxyfuran (XI) with two extra groups, that is, 2-methyl and 3-methoxycarbonyl groups (Figure 2, C).…”

“…Scheme 1 Approach to naphthalene scaffolds characteristic to 1 and 2 Scheme 2 Three precedents for furan-benzyne cycloaddition (1) Reactivity: Although furans are generally less reactive dienes in Diels-Alder reactions, their [4+2] reactions with arynes have been well documented 4 thanks to the high reactivity of the latter species by the unusually low-lying LUMO (Scheme 2, A). 5 (2) Regioselectivity: If one considers substitution patterns of the two alkoxy groups of two reaction partners I and II (Scheme 1, highlighted in red), one could expect a favorable regioselectivity by the literature precedent 6 of βalkoxyfuran III and α-alkoxybenzyne IV (Scheme 2, B).…”

Benzo[a]heptalenes from Heptaleno[1,2‐c]furans. Part 2

“…The established condition, Ac 2 O/H 2 SO 4 at room temperature [18], gave the expected benzo[a]heptalene-2,3-diol diacetates 20a and 20b, respectively, in acceptable yields if one takes into account that in the case of the reaction of 1a with AAN also the 1,4-epoxybenzo[d]heptalen-2(3H)-one 18a (ca. 40%) was formed, which does not rearrange and is mostly destroyed under the reaction conditions.…”