Syntheses of 6,7‐Benzotropolone by Using Ring‐Closing Metathesis Variants Obviating a Strongly Acidic Hydrolysis Thereafter

Abstract

A Wittig reaction of 3‐hydroxyphtalide (11) gave ortho‐styrene‐2‐carboxylic acid (12). Its Weinreb amide 13 acylated heterosubstituted methyllithiums. This led to aryl “methyl” ketones whose sp3‐carbon was substituted by Cl+OMe (in 14 a), 2×Cl (in 14 b), OtBu (in 17 a), SPh (in 17 b) or SO2Ph (in 17 c). The enolates of these ketones were C‐allylated. This furnished the benzene‐fused nona‐1,8‐dienones 7 a–b and 9 a–c, respectively. Ring‐closing metatheses provided the corresponding benzocycloheptadienones 8 a‐b and 10 a–c. Their ketone moieties were α,α‐disubstituted (in 8 a–b) or α‐monosubstituted (in 10 a–c). Each substitution pattern allowed to generate the hydroxyenone motif of the corresponding benzocycloheptatrienone—or 6,7‐benzotropolone—6 a: The MeO‐ and PhS‐containing benzocycloheptadienone 8 a gave 6,7‐benzotropolone methyl ether (15) by sulfoxide formation and pyrolysis; 15 was demethylated with BCl3. The same intermediate resulted from the dichlorobenzocycloheptadienone 8 b and NaOMe. The benzocycloheptadienone 10 a was de(tert‐butylated) with formic acid; a subsequent Pfitzner‐Moffatt oxidation completed 6,7‐benzotropolone (6 a) once more. The PhS‐containing benzocycloheptadienone 10 b was α‐acetoxylated with Pb(OAc)4; the resulting O,S‐acetal gave 6,7‐benzotropolone (6 a) by hydrolysis. The PhSO2‐containing substrate 10 c was deprotonated whereupon an oxidation with Me3Si−O−O−SiMe3 gave 6,7‐benzotropolone (6 a).

Syntheses of 9‐Vinylated Benzotropolones by a Sequence of Acylation, Ring‐Closing Enyne Metathesis, and Oxidation

“…The reaction mixture was stirred at this temperature for 20 h and was then filtered over SiO 2 (d = 3 cm, h = 10 cm) using EtOAc (180 mL). The solvent was evaporated under reduced pressure and the residue was purified by flashchromatography [13] 4.99 (ddt, J 4'À H, 5'À B = 10.2 Hz, 2 J 5'À A,5'À B = 1.3 Hz 4 J 3'À H,5'À B = 1.3 Hz, 1H, 5'-H B ), 5.06 (ddt, J 4'À H,5'À A = 17.1 Hz, 4 J 3'À H,5'À A = 1.7 Hz, 2 J 5'À B,5'À A = 1.7 Hz, 1H, 5'-H A ), 5.88 (ddt, J 5'À A,4'À H = 17.0 Hz, J 5'À B,4'À H = 10.4 Hz, J 3'À H,4'À H = 6.6 Hz, 1H, 4'-H), 6 i The indicated 13 C nuclei were identified in an edHSQC spectrum ("short range C,H-COSY spectrum"; 500.30/125.80 MHz, CDCl 3 ) by their cross peak with directly bonded protons which had been previously assigned unequivocally; ii The indicated 1 H or 13 C nuclei were identified in a HMBC spectrum ("long range C,H-COSY"; 500.10/125.75 MHz, CDCl 3 ) by their cross peaks due to 2 J C,H or 3…”

“…A solution of 7-[(trimethylsilyl)oxy]-10-vinyl-7,8-dihydro-6Hcyclohepta [3,4]benzo[1,2-d]-1,3-dioxol-6-one (33; 31 mg, 0.1 mmol) in Et 2 O (1.8 mL) and MeOH (0.6 mL) was treated with aq. HCl (1 m, 0.6 mL, 6 eq.)…”

“…The solution was stirred for 30 min at 0 °C and was then cooled to À 78 °C. A solution of 10-vinyl-7,8-dihydro-6H-cyclohepta [3,4]benzo[1,2-d]-1,3-dioxol-6-one (15; 71.5 mg, 0.31 mmol) in THF (3.1 mL) was added slowly at À 78 °C. After stirring for 1 h at this temperature Me 3 SiCl (60.0 μL, 0.47 mmol, 1.5 eq.)…”

“…[3] In addition, we converted 6,7,8-tri-unsubstituted benzotropolones into 6-or 7-or 8-substituted benzotropolones via the methyl ethers of 7-, 8-or 9-bromobenzotropolone and Pdcatalyzed cross-couplings thereof. [4] Very recently, we embellished these RCM approaches to benzotropolones 4 [2] by our hitherto possibly mildest variant. [5] Moreover, we developed a 3-step ring-expansion of tetralones giving benzotropolones again differently than before.…”

“…H NMR (400.13 MHz, CDCl 3 ): δ = 2.36 (m c , 2H, 8-CH 2 ), 2.87 (m c , 2H, 9-CH 2 ), 5.10 (ddd, J 1'À H,2'À B = 10.8 Hz, 2 J 5'À A,5'À B = 1.3 Hz, 5 J 7À H,5'À B = 0.6 Hz, 1H, 2'-H B ), 5.19 (dd, J 1'À H,2'À A = 17.4 Hz, 2 J 5'À B,5'À A = 1.3 Hz, 1H, 2'-H A ), 6.07 (s, 2H, 2-CH 2 ), 6.21 (dt, J 8À H,7À H = 7.6 Hz, 5 J 5'À B , 7À H = 0.6 Hz, 1H, 7-H), 6.43 (ddd, J 2'À A,1'À H = 17.4 Hz, J 2'À B,1'À H = 10.8 Hz, 4 i the indicated nuclei were identified in an edHSQC spectrum ("short range C,H-COSY spectrum"; 400.13/100.61 MHz, CDCl 3 ) by their cross peak with directly bonded protons which previously were assigned unequivocally; ii The indicated nuclei were identified in a HMBC spectrum ("long range C,H-COSY"; 400.13/100.61 MHz, CDCl 3 ) by their cross peaks due to 2 J or 3 J couplings with more distant protons; indicated 1 H-NMR signals could be assigned unequivocally due to the mentioned cross peaks.…”