A New Synthesis of Benzofurans from Phenols via Claisen Rearrangement and Ring‐Closing Metathesis

Abstract

Based on Claisen rearrangement, the double bond isomerization of O-allyl function together with the formation of O-vinyl function in one pot, and ring-closing metathesis (RCM), various phenols were transformed into various benzofurans in good yields. these allyl aryl ethers (2a-f) were heated to reflux in decalin to undergo Claisen rearrangement to produce O-allyl phenols (3a-h) in 80-87% yields, respectively. Compound 2e or 2f, which is the same compound, gave compound 3e, orthoproduct, and para-product 3f in yields of 50% and 40% after undergoing Claisen rearrangement, respectively. The structural determination and discrimination of compound 3e and 3f can be easily made by 1 H-NMR. For example, 3f has three aromatic protons including a doublet signal of one proton at d 7.21 with coupling constant J = 7.8 Hz indicating the ortho couple of H-5, a double doublet signal of one proton at d 7.47 with a coupling constant of J = 7.8, and 1.8 Hz indicating ortho couple and meta couple of H-6, and a doublet signal of one proton at d 7.55 with a coupling constant of J = 1.8 Hz indicating the meta couple of H-2. On the other hand, the aromatic region of 3e reveals a multiplet signal of one proton centered at d 6.99 and a multiplet signal of two protons centered at d 7.16. Thus, it matches the previous studies reported by Bruce, et al. 14 Followed by utilizing a phase transfer catalyst, tetrabutyl ammonium bromide (TBAB), and a large excess amount of dichloroethane in aqueous NaOH (20%), O-allyl phenols (3a-h) smoothly underwent SN2 substitution to give exclusively monoalkylated products, 1-allyl-2-(2chloroethoxy)benzenes (4a-h) in good yields. The structure elucidation of compound 4a-h can be easily made by EI-MS and 1 H-NMR. For example, compound 4a not only has the correct M + , it also has a ratio of relative intensity of M + /M +2 in 3/1 in EI-MS, indicating one chlorine atom in the molecule. Furthermore it exhibited two two-proton signals with triplets at d 3.78 and 4.19 having the same coupling constant of 5.8 Hz, clearly indicating the protons of OCH 2CH2Cl, and OCH 2 CH 2 Cl in the molecule, respectively. By treating 4a-h with potassium tert-butoxide in THF at reflux, it underwent 1,2-elimination to diminish HCl from the molecule of 4a-h, and concomitantly underwent the double bond isomerization to give 5a-h in good yields. In our reaction condition, the new double bond isomerized from allyl group to conjugate with the benzene ring is obtained thermodynamically in transform. The structure elucidation of compound 5a-h can be easily identified by spectra data, especially by 1 H-NMR. For instance, compound 5a exhibited one methyl signal at d 1.89 (dd, J = 6.6 Hz, 1.6 Hz, 3H, CH=CHCH3), one oleifinic signal at d 6.25 (dq, J = 15.8 Hz, 6.6 Hz, 1H, CH=CHCH 3 ), and one oleifinic proton at d 6.66 (dq, J = 15.8 Hz, 1.6 Hz, 1H, CH=CHCH 3). Due to the oleifinic coupling constant, J = 15.8 Hz of the propenyl group, the isomerization of double bond to trans-form configuration can be clarified. Because the oleifinic chemical s...

Isomerization of Allylbenzenes

“…In another example from the van Otterlo group, a “double” isomerization strategy on the bis-allyl substrates 577 readily afforded compounds 578 , in which, most interestingly, both the O - and the C -allyl groups were isomerized as illustrated in Scheme . These compounds were then facilely converted into their respective substituted benzofurans 579 by RCM, in generally acceptable yields. ,, A related approach was employed by Wang and co-workers, with the difference being that they generated the substituted benzofurans from bisalkenes, which in turn were generated by potassium butoxide-mediated isomerization and elimination reactions as also shown in Scheme . , The Wang group transformed ethers 580 into the conjugated ethers 581 followed by RCM with the Grubbs first generation catalyst GI using an essentially similar approach to afford their benzofurans and applied this strategy in their further work on substituted coumarins , and 2,5-dihydro­[ b ]­oxepines (not illustrated).…”

“…320,733,736 A related approach was employed by Wang and co-workers, with the difference being that they generated the substituted benzofurans from bisalkenes, which in turn were generated by potassium butoxide-mediated isomerization and elimination reactions as also shown in Scheme 150. 737,738 The Wang group transformed ethers 580 into the conjugated ethers 581 followed by RCM with the Grubbs first generation catalyst GI using an essentially similar approach to afford their benzofurans and applied this strategy in their further work on substituted coumarins 739,740 and 2,5-dihydro[b]oxepines 741 (not illustrated). The strategy used by the van Otterlo group was amended to afford nitrogen-containing annulated compounds, albeit with less success.…”

Structural Features Defining NF-κB Inhibition by Lignan-Inspired Benzofurans and Benzothiophenes

“…Unfortunately, the direct arylation reaction did not take place and only product 15 derived from competing Mizoroki-Heck coupling was found, instead. Hence, the alternative approach using 5-chlorobenzo[b]furan 17 as starting material was investigated (Scheme 2) [24,28]. In our previous publication [10], it was observed that aryl chlorides were unreactive as coupling partners under the reaction conditions and, hence, homo-coupling of the benzofuran starting material should not be an issue.…”

“…In our previous publication [10], it was observed that aryl chlorides were unreactive as coupling partners under the reaction conditions and, hence, homo-coupling of the benzofuran starting material should not be an issue. Hence, the alternative approach using 5-chlorobenzo[b]furan 17 as starting material was investigated (Scheme 2) [24,28]. In our previous publication [10], it was observed that aryl chlorides were unreactive as coupling partners under the reaction conditions and, hence, homo-coupling of the benzofuran starting material should not be an issue.…”