Dihydrobenzofuran 3 + 2 cycloaddition

Stable cA-1-phenyl-1-cyclohexene 24 photodimeiizes via Diels Alder cycloaddition to trans adduct 25 (Equation 1.33) [66] and the photoexcitation of dihydrobenzofuran-fused cyclohexenone 26 in net furan gives the trans fused Diels-Alder adduct 27 (Equation 1.34) [67]. 

Other examples of the iodonium ylide-based syntheses of furan derivatives involve cycloaddition reactions with alkenes or alkynes. Although the majority of these syntheses involve stable iodonium ylides (86JOC3453 94T11541) (e.g., Eqs. 16 and 17), in some cases the ylides are unstable and are generated in situ (92JOC2135) (e.g., Eq. 18). In the case of alkenes, dihydrofuran derivatives are obtained (Eqs. 16-18). This synthetic route is especially useful for the synthesis of dihydrobenzofuran derivatives that are related to the neolignan family of natural products (Eq. 18). 

The direct electrochemical oxidation of phenols generates phenoxonium cations which are able to undergo [3-1-2] cycloaddition in the presence of unactivated alkenes to produce benzofurans <1999JOC7654>. Thus, electrolysis of methyl 2,5-dihydroxybenzoate in a solution of lithium perchlorate in nitromethane in the presence of acetic acid and 2-methyl-2-butene produces the dihydrobenzofuran in excellent yield (Equation 88). 

On the other hand, PIFA-induced oxidation of p-methoxy-substituted phenols (15) in the presence of electron-rich styrene derivatives (16) resulted in new carbon-carbon bond formation via an intermolecular 1,3-cycloaddition to afford frazzs-dihydrobenzofurans (17) stereoselectively [35,36] [Eq. (4)]. A formal synthesis of neolignans such as kadsurenone (18) and denudatin B (19) was achieved by this methodology. 

The BF3-catalyzed reaction of a-aminoaldehydes with 10 is valuable for highly stereoselective synthesis of 2,3,5-trisubstituted pyrrolidines with all -cis configurations (Equation (50)).197 The stereochemical outcome like chelation-controlled stereochemistry might result from the inherent conformational arrangement of the aldehyde-BF3 complex. />-Quinoneimines, o-quinones, and a-alkoxyhydroperoxides undergo similar types of [3 + 2]-cycloadditions with allylsilanes to afford dihydro indoles, dihydrobenzofurans, and 1,2-dioxolanes, respectively.164,175,198... 

By using a stoichiometric amount of the chiral titanium reagent prepared by mixing chiral diol, Titanium IV) Chloride, and titanium tetraisopropoxide, the asymmetric [2 + 2] cycloaddition reaction of 1,4-benzoquinones and styrenes gives the corresponding cyclobutane derivatives with high optical purity. These rearrange to 2,3-dihydrobenzofuran derivatives on mild acid treatment (eq 13). ... 

Titanium Lewis acids effect formal [2 + 2] cycloaddition as shown in Eqs (158) [401] and (159) [402,403]. Subtly changing the reaction conditions and substrates alters the product of Eq. (159) from the cyclobutane to a dihydrobenzofuran derivative, as will be described below. The analogous hetero [2 + 2] addition of a chiral aldehyde to a silylketene proceeded stereoselectively in the presence of titanium tetrachloride to give the propiolactone, as shown in Eq. (160) [404]. The silyl group was removed by the treatment with KF. 

Engler reported [2 + 2] cycloaddition of 1,4-benzoquinones with styrenes using TAD-DOL-Ti complex. The [2 + 2] cycloaddition products can, upon warming the reaction mixture, be transformed to the formal [2 + 5] cycloaddition products, dihydrobenzofur-ans, although with reduced %ee. The dihydrobenzofurans thus obtained are useful intermediates in the synthesis of biologically interesting natural products (Sch. 59) [141]. 

Certain olefinic substrates undergo thermally-forbidden [2 + 2] type cycloaddition in the presence of Lewis acid catalysts through coordination to the acceptor molecules. Scheme 111 illustrates the enantiose-lective version of this reaction (277). Some thio acetylenes can also be used. Substantial asymmetric induction has been observed in cycloadditions of styrenes and 1,4-benzoquinones using a stoichiometric amount of a chiral Ti(IV) complex (272). The [2 + 2] cycloadducts are readily rearranged to 2-aryl-2,3-dihydrobenzofurans. 

Aryl-2,3-dihydrobenzofurans The [3+2]cycloaddition of benzoquinones with styrenes is high yielding, and it has been applied to the synthesis of ptero-carpans and neolignans. 

Other cycloadditions. A [3+2]-cycloaddition involving a benzoquinone and an alkene to give 2,3-dihydrobenzofuran derivatives, and an intramolecular [4+3]-cycloaddition to provide functionalized polycyclic compounds, are further demonstrations of the utility of LiClQj-OEtj. The reaction of aromatic or a,p-unsaturated aldehydes with acid chlorides proceeds via ketenes and then 2-oxetanones. ... 

A thermal, Lewis acid-catalysed [3+2] cycloaddition of allylsilanes giving the dihydrobenzofurans 57 has also been described (equation (3)) (02TL5349). The mechanism has been interpreted in terms of formation of a p-silyl cation by a zinc-benzoquinone complex, followed by cyclisation, and elimination of isobutene when R = Bu. 

For the preparation of 2,3-dihydrobenzo[6]furans, several strategies have been developed. The acid-catalyzed cycloaddition of styrenes (e.g., (135)) with quinone monoketals is suitable for the synthesis of both 2,3-dihydrobenzofurans and the quinonoid derivatives (Scheme 93) <77JA8073,... 

Chiba K, Fukuda M, Kim S, Kitano Y, Tada M (1999) Dihydrobenzofuran synthesis by an anodic [3 -l- 2] cycloaddition of phenols and unactivated alkenes. J Org Chem 64 7654-7656... 

The asymmetric [2 + 2] cycloaddition of 1,4-benzoquinones with styrenes can be furnished using 5 equiv of TADDOL-TiCl2 complex to give the corresponding cyclobutane derivative with 90% ee that can be transformed to a dihydrobenzofurans upon warming with some loss of enantioselectivity [185] (Scheme 14.82). 

When la was heated with the less reactive isoprene 5 in a sealed ampoule at 150-200°C for 72 h using benzene as solvent, it showed its dienophilic character taking part in the DA cycloaddition reactions. The reactions proceeded to produce the mixture of isomeric benzofurans 10a and 10b as the principal products and dihydrobenzofurans 9a and 9b (global yield 62%) (Della Rosa, et al, 2005). (Figure 2) In the same manner, in the case of 1-tosyl-2-nitropyrrole 2a, it reacted with isoprene furnishing dihydroindole isomers lla,b and... 

A series of 5-aminobenzofurans 170 and 2,3-dihydrobenzofurans 172 were successfully prepared from the reactive precursor, quinone monoamines 168, readily obtained through the DIB or PIFA-mediated oxidation of p-ami-nophenols 167 (Scheme 42). Reaction of quinone monoamine with ketene acetals 169 afforded the corresponding benzofurans [59]. Using this strategy, Barret et al. independently reported the synthesis of 2,3-dihydrobenzofurans 172 via [3+2] cycloaddition reaction of quinone monoamines with various azadienes 171. The utility of the developed protocol was demonstrated for the construction of 2,3-dihydrobenzofurans containing an adrenergic agent, Efaroxan 173 [60]. 

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