Ring synthesis benzofuran

In the synthesis of morphine, bis-cyclization of the octahydroisoqtiinolinc precursor 171 by the intramolecular Heck reaction proceeds using palladium trifluoroacetate and 1,2,2,6,6-pentamethylpiperidine (PMP). The insertion of the diene system forms the rr-allylpalladium intermediate 172, which attacks the phenol intramolecularly to form the benzofuran ring (see Section 1.1.1.3). Based on this method, elegant total syntheses of (-)- and (+ )-dihydrocodei-none and (-)- and ( + )-morphine (173) have been achieved[141]. 

An intramolecular Heck cyclization strategy was developed for the construction of indole and benzofuran rings on solid support [82], enabling rapid generation of small-molecular libraries by simultaneous parallel or combinatorial synthesis. Sn2 displacement of resin-bound y-bromocrotonyl amide 97 with o-iodophenol 96 afforded the cyclization precursor 98. A subsequent intramolecular Heck reaction using Jeffery s ligand-free conditions furnished, after double bond tautomerization, the resin-bound benzofurans, which were then cleaved with 30% TFA in CH2CI2 to deliver the desired benzofuran derivatives 99 in excellent yields and purity. 

The synthesis of photochromic compounds containing combinations of benzothiophene and thiophene 70 (04JPP(A)97, 09JMS100), indene 71 (06TL1267), or benzofuran rings 72 and 73 (06BCJ1100, 08BCSJ644) was documented (Scheme 22). 

Synthesis of a benzofuran ring was successfully realized from 0-arylated oximes in the presence of acidic catalyst (Fisher method) For example, oximes 24 in the presence of a mixture of trifluoroacetyl triflate (TFAT) and 4-dimethylaminopyridine (DMAP) in CH2CI2 at room temperature afforded 2-arylbenzofurans (25) in yields up to 99% (equation 11). ... 

Unlike in the case of the preparation of indoles and benzofuranes, the synthesis of benzothiophenes from o-ethynyl-thiophenols is not known. A close analogy was reported by Larock, where phenylacetylene was coupled with 2-iodothioanisole. Ring closure of the formed o-ethynyl-sulfide was initiated by the addition of different electrophiles. The reaction led to the formation of the benzothiophene core bearing the electrophile in the... 

Coumestans,21 although they have a fused benzofuran ring, will be surveyed as being 8-lactones of 2-(2-hydroxyphenyl)-3-benzofuran carboxylic acids [coumestrol (4)22 is the 8-lactone of 2-(2,4-dihydroxy-phenyl)-6-hydroxy-3-benzofurancarboxylic acid]. The synthesis of some rotenoids 23 from benzofuran derivatives will also be reviewed, but dibenzofuran derivatives, such as usnic acid and its derivatives, will not be treated. 

This occurs for 2-hydroxyphenylacetones, hydroxylated deoxy-benzoins, and, as in the simplest case (R=H), o-hydroxyarylacetal-dehydes. The reaction is especially suitable for the synthesis of polyheterocyclic compounds with fused benzofuran rings. 

The synthesis of the (i) 4-hydroxy-6-methoxytetrahydrofuro[2,3-6]-benzofuran ring (116), a degradation product of natural substances of the sterigmatocystin series, is similar,318 as is the synthesis of the dihydro derivative (117) from the o-acetylated acetaldehyde (118), a nonisolated intermediate which is ring-closed to 119 and then heated in toluene to give 117. The last is the starting point for the synthesis of aflatoxin M4 (49).153... 

The preceding sections described the newer methods for the synthesis of furan and its derivatives. This section snmmariy.es the best practical methods for the synthesis of the parent furan and benzofuran ring structures and their substituted derivatives. It is from furfural that furan itself is prepared industrially by the catalytic decarbonylation in steam. 

Bcnzofuran-4,7-dioncs have been synthesized regioselectively by [3 + 2] photoaddition of 2-hydroxy-1,4-benzoquinones with a range of alkenes (equation 185)664. The reaction occurs in 30-60% yield and is a useful method for the synthesis of the benzofuran ring system, which is important in natural products like acamelin665. Substituted naphthoquinones may also be used in this reaction666,667 and this has lead to a very simple two-step synthesis of maturinone. In a similar reaction, a [3 + 2] photoaddition reaction of 2-amino-1,4-naphthoquinones with electron-rich alkenes gave 13-82% yields of 2,3-dihydro-177-bcn/ /]indole-4,9-diones in a single-step process which involved photolysis followed by oxidation (equation 186)668,669. 

The Stork group reported the synthesis of racemic codeine and thebaine utilizing the intramolecular Diels-Alder reaction as the key transformation in 2009 [45]. The key features of their synthesis are (1) a direct construction of a phenanthrofuran skeleton (A-B-C-E tetracyclic system) by the intramolecular Diels-Alder reaction of a diene tethered to the benzofuran ring and (2) a formation of the D-ring by the intramolecular SN2 reaction of an amino-mesylate. 

Fusion of a benzofuran ring across the 5,6-bond (/face) of naphtho[l,2-b]pyrans to afford 48 brings about a red shift > 20 nm of the higher absorption band. The synthesis involves reaction of naphthoquinone with a methoxyphenol and subsequent propargylation of the resulting naphtho[l,2-b][l]benzofuran. The benzofuran is effectively acting as the bulky 5-... 

The fast fade rate shown by 2-(4-trifluoromethyl)-2-phenyl-5-trifluorophenyl-[l]benzofuran[2,3-(]naphtho[l,2-6]pyran is attributable to the bulky 5-substituent rather than to the fused benzofuran ring <01WOP36424>. Its synthesis follows from the preparation of 9-hydroxy-7-trifluoromethylbenzo[6]naphtho[ f]furan from 4-chloromethyldibenzofuran (Scheme 18). 

The synthetic strategy involving an intramolecular hydroxyl epoxide opening was applied to build up the cyclopenta[i)]benzofuran ring for the total synthesis of the naturally occurring rocaglaol <04OL4595>. 

An efficient, one pot method for the synthesis of benzo[f ]fluoren-10-ones was achieved by CSjCOj promoted sequential deprotonation and cyclization. The benzofuran ring was generated by an intramolecular acylation of an enolate <01TL8429>. 

Mehta and Likhite used a Lewis acid-catalyzed cyclization route to construct the benzofuran ring system of frondosin B, an IL-8 antagonist, and an inhibitor of protein kinase C (PKC). Treatment of a highly functionalized chiral ketone precursor with boron trifluoride-diethyl etherate gave the corresponding furan in 95% yield over two steps. This strategy was also employed by Ovaska and Li in their synthesis of the same compound. ... 

Zn-carbonate and NaHCOg ground together, suspended in methylene chloride, 2-carbethoxy-3-bromocyclopent -2- enone and 3a, 4-dihydroxy-6-methoxy-3a, 8a-di-hydrofuro[2,3-b]benzofuran added, and stirred 20 hrs. at room temp, under Ng rac. aflatoxine M. Y 32%. - This new coumarin ring synthesis is particularly useful with acid-sensitive phenols, when the classical Pedimann synthesis is not applicable. F. e. s. G. Biichi and S. M. Weinreb, Am. Soc. 93, 746 (1971). 

Cope Elimination Reaction Cope Rearrangement Corey-Bakshi-Shibata Reduction Corev-Kim Oxidation Corey-Winter Olefin Synthesis Comforth Rearrangement Coumarin-Benzofuran Ring Contraction Crafts (see Friedel-Crafts Reaction)... 

Larocket fl/. in 2000 developed the fluoren-9-one synthesis by the cyclocarbonyla-tion of ort/zo-halobiarys with a commercially available Pd(PCy3)2 catalyst [17] This procedure was initiated by the palladium(0) and could be utilized to the synthesis of polycyclic and heterocyclic fluorenones containing the fused isoquinoline, indole, pyrrole, thiophene, benzothiophene, and benzofuran rings (Table 15.12). 

Secoquettamine (234) and dihydrosecoquettamine (235) together with their probable biogenetic precursor quettamine (236) form a small group of alkaloids. They were isolated by Shamma et at. (179) from Berberis baluchista-nica in yields of 0.00036,0.00017, and 0.0012%, respectively. These alkaloids incorporate either a benzofuran or a dihydrobenzofuran ring within the molecular framework, and the seco ones possess the /V,W-dimethylaminoethyl substituent. The structures of these bases were determined on the grounds of spectral data as well as by total synthesis. There is one chiral center at C in dihydrosecoquettamine (235) however, the base was isolated in the form of a racemic mixture (179). 

---