Benzofurans 3-vinyl

A wide variety of other functional groups can be employed in these annulations. For example, this chemistry has been extended to the synthesis of 1,2-dihydroisoquinolines, benzofurans and benzopyrans (Scheme 3).3 One can also employ vinylic halides and triflates in this process.4... 

Rawal s group developed an intramolecular aryl Heck cyclization method to synthesize benzofurans, indoles, and benzopyrans [83], The rate of cyclization was significantly accelerated in the presence of bases, presumably because the phenolate anion formed under the reaction conditions was much more reactive as a soft nucleophile than phenol. In the presence of a catalytic amount of Herrmann s dimeric palladacyclic catalyst (101) [84], and 3 equivalents of CS2CO3 in DMA, vinyl iodide 100 was transformed into ortho and para benzofuran 102 and 103. In the mechanism proposed by Rawal, oxidative addition of phenolate 104 to Pd(0) is followed by nucleophilic attack of the ambident phenolate anion on o-palladium intermediate 105 to afford aryl-vinyl palladium species 106 after rearomatization of the presumed cyclohexadienone intermediate. Reductive elimination of palladium followed by isomerization of the exocyclic double bond furnishes 102. 

It was shown <1998CCC681> that [l]benzothieno[3,2-3]furan 60, due to its low furan aromaticity, possesses dienophilic behavior and reacts with electron-rich dienes with the formation of a new heterocyclic system [l]ben-zothieno[3,2-3][l]benzofuran 93. Furthermore, it was reported <1999CCC389> that introduction of a vinyl moiety at C-2 of 57 created a reactive diene 94, which reacted with various dienophiles. Thus, both cycloaddition reactions led to new derivatives of heterocycle 93 substituted in the benzofuran part of the heterocyclic system (Scheme 10). 

Tetrahydrobis(benzofuran) is produced by a tandem cyclization reaction from the bis-vinyl ether on reaction with catalytic quantities of rhodium(l) salts in the presence of electron-rich phosphine ligands <20030L1301>. Thus, employing 10mol% of [RhCl(coe)2]2 with 20mol% of a dicyclohexyl ferrocenyl phosphine ligand produces the bis-cyclized product (coe = cyclooctene Equation 67). 

Dihydrofuran (used as the vinyl ether), condenses with 2-acetyl-1,4-benzoquinone to give tetrahydrofuro[2,3-6]benzofuran (144), which is found in natural benzofuranoid xanthones (sterigmatocystin).372... 

The Pechmann synthesis is unsuitable for acid-sensitive phenols, as for example the furo[2,3 -6]benzofuran derivative (373). An alternative approach uses the enhanced electrophilic character of a vinyl bromide in the presence of zinc carbonate to construct a suitable side-chain adjacent to the phenolic group (71JA746). In the examples cited, ring closure occurred under the mild conditions to form the pyranone ring of the aflatoxins (374). Since neither sodium nor potassium carbonate proved effective, it was considered that chelation of the zinc facilitated the carbon-carbon bond formation (Scheme 115). 

Fig. 8 2-Vinylthieno[3,2-h][l]benzofuran (60), 2-vinyl[l]thieno[3,2-h][l]benzothiophene (61), 2-vinylthieno[3,2-h]thiophene (62)...

The kinetic resolution of racemic l-(benzofuran-2-yl)ethanol rac-33 having different substituents on the benzene was reported ring using lipase-catalyzed transesterification with vinyl acetate as acyl donor. The reaction afforded (lA)-l-acetoxy-l-(benzofuran-2-yl)ethanes (A)-34 and (16)-l-benzofuran-2-yl)ethanols (S)-33 in highly enantiopure form.65... 

The industrial synthesis of vinyl acetate [14] via palladium-catalyzed oxidative coupling of acetic acid and ethene using direct 02 reoxidation has already been mentioned (Scheme 3, d). Some NaOAc is required in the reaction medium, and catalysis by Pd clusters, as alternative to Pd(II) salts, was proposed to proceed with altered reaction characteristics [14]. Similarly, the alkenyl ester 37 (Table 5) containing an isolated vinyl group yields the expected enol acetate 38 [55] whereas allylphenol 39 cyclizes to benzofuran 40 with double bond isomerization [56]. 

Cross-coupling reactions are also possible as an extension of this type of domino process - with excess vinyl bromide 19 either benzofurans 20 or indenes 21 are obtained as mixtures of double-bond isomers [5, 6]. 

During the laser flash photolytic conversion of the vinyl bromide 365 into the benzofuran, a transient broad peak (400-650 nm) was observed and was assigned to the cationic transition state model compound for the in-plane vinylic S sr2 reaction (Scheme 85). This interpretation is supported by calculations at the B3PW91 /6-31 C(d) level <2005OL2739>. 

As an extension of this work, photoinduced [2+2]-cycloadditions of 1-acetylisatin (13) with cyclic enolethers (furan, benzofuran, 2-phenylfuran, 8-methoxypsoralen), and acyclic enolethers (//-butyl vinyl ether and vinyl acetate) were investigated which afforded the spiro-oxetanes in high yields (82-96%) and with high regio- and diastereoselectivity (Sch. 4) [19]. Treatment of the furan-derived oxetane 15 with acid resulted in oxetane ring opening and yielded the 3-(furan-3-yl)indole derivative 16. 

A complex of homoadamantyne (273) has been prepared by dehalogena-tion of 272 in the presence of tris(triphenylphosphine)platinum(0) [Eq. (43)]." Trapping free homoadamantyne was presumed to be the mechanism of this reaction. However, reduction of neither an initially formed 77-com-plex2,82 nor a C-Br insertion product93 was excluded. Interestingly, the free alkyne, generated by dehydrohalogenation of the vinyl bromide, was successfully trapped with diphenyl-wo-benzofuran. 

In suitable vinylic halides, nucleophilic photosubstitution occurs intramolecular- 295-297,324,330-332 por jnstance irradiation of 113 in methanol only yields benzofuran 114, and no vinyl ether product or 1,2-aryl rearrangement products are formed (equation 84a)296. Apparently, the reaction with an internal nucleophile is faster than the 1,2-aryl shift and also faster than the reaction with an external nucleophile. With the less stabilized vinyl cations derived from the a-methyl- and a-H-analogues of 113-OMe, 1,2-aryl shifts do... 

Finally, the a,/ -unsaturated carbene complex may be generated in situ by alkyne insertion into a chromium-carbene bond of a saturated chromium carbene leading to a chromium vinyl carbene (equivalent to intermediate (f )-D in the mechanism of the benzannulation reaction, see Section 8.2.1, Scheme 3), which may undergo subsequent benzannulation with a second equivalent of the alkyne [43a]. This strategy was subsequently applied to the synthesis of (Z)-enediynes and related compounds [43b], and to that of substituted benzofurans (see also Section 8.5) [43c, 43d]. 

There are a few examples of polymers based on vinylbenzofurans. Vinyldibenzofuran 324 has been patented for use in copolymer formulations with other vinyl arenes, used to prepare light-emitting devices <2004USP6803124>. Benzofuran 325 was developed as one of four polymerizable monomers that contain a built-in antioxidant. The polymerization process was transition metal catalyzed <2003MM8346>. Benzofuran 326 also contains the styrene substructure, but there are few examples of its polymerization. Poly(2,3-benzofuran) films were synthesized by anodic oxidation on stainless steel in the presence of boron trifluoride etherate. The films had good thermal stability and conductivity of lO Scm <2005MI1654>. 

For example, the C-C bond in [( -biphenylene)Mn(CO)3]+ is rapidly broken by the mildly nucleophilic Pt(PPh3)3. The same is true of the vinylic C-0 bond in benzofuran, in which an intermediate could be observed containing the Pt(PPh3)2 unit r-bonded to the furan C=C prior to fission of the adjacent C-0 bond, as shown in Scheme 21. 

If this cyclization is carried out in the presence of catalytic amounts of ( —)-/3-pinene, optically active products can be formed. Thus if the cyclization of the allylphenol 1 is conducted in the presence of Pd(OAc)2 (1 mmole), Cu(0Ac)2 H20 (lOmmole), and (-)-/3-pinene (1 mmole), an excess of (S)-2,3-dihydro-2-vinyl-benzofurane (2) is formed in 12% optical yield. Surprisingly, if /3 -pinene is present in larger amounts (2 mmoles), the cyclization does not proceed. ... 

Z)-2-Butenyl]phenol, on the other hand, gives only 0.7 % ee of the (R)-2,3-dihydro-2-vinyl-benzofuran. The difference in optical yields between the (E)- and (Z)-isomeric substrates must be due to the geometric difference, since no Z-> isomerization of the double bond occurs during the reaction. 

Alcohols add to alkynes under certain conditions to give vinyl ethers. In an excess of alcohol, and in the presence of a platinum catalyst, internal alkynes are converted to ketals. " The alcohol to alkyne addition reaction is quite useful for the preparation of heterocycles. Dihydrofurans, " furans, " benzofurans, " and pyran... 

In 2002, Trost and Tang reported the chiral total synthesis of (-)-codeine in short reaction steps using a palladium-catalyzed asymmetric allylic alkylation (AAA) [53] as the key transformation [54], In 2005, a detailed full account of their synthesis was published [55]. The key features of their synthesis are (1) a preparation of an aryl ether with high optical purity by the Pd-catalyzed AAA reaction, (2) the intramolecular Heck reaction to generate the A-C-E benzofuran skeleton, (3) the second intramolecular Heck reaction of Z-vinyl bromide providing the phenan-throfuran core, and (4) the intramolecular hydroamination for the construction of D-ring by the action of LDA and visible light. 

Diimide reduction of 96, obtained by the enzymatic oxidation of 95 (96% ee) [67], followed by O-acetylation afforded cyclohexene-diol 97 in 47% yield (Scheme 19). Compound 97 was converted into carbamate 98 by S 2 reaction with methylamine and subsequent urethane formation. Regioselective protection of the diol in 98 with TBSC1 afforded 99, which was coupled with bromoisovanillin 54 under the conditions of Mitsunobu to provide 100 (see Sect. 2.2.2). The intramolecular Heck reaction of 100 constructed the benzofuran ring including a quaternary center to afford 101 in 82% yield. Wittig reaction of 101 with Ph3P=CHBr generated vinyl bromide 102 in 49% yield as a mixture of E- and Z-isomers (E Z = ca. 1 2). 

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