Tricyclic furan

DinitrQ-ll-Qxatricyclo[6 2 1 0 undec-9-ene has been prepared by an intramolecular Diels-Alder reacdon of the furan with a idtroalkene group as shown in Eq 8 26 This tricyclic compound is a versatile synthedc tool for the preparadon of ergot alkaloids... 

Intramolecular cycloadditions of furans are a useful method for creating an oxygenated cyclohexane ring in rigid cycloadducts. Thus, a MeAICI2-catalyzed intramolecular reaction [40] of compounds 34 leads stereoselectively to tricyclic cycloadducts (Equation 3.8). The reaction yield is strongly dependent on the quantity of the catalyst and the type of substituent at the olefmic double bond. Cycloadduct 35 (R = R2 = Me, Ri = R3 = R4 = H) was then converted [40b] into 1,4-epoxycadinane (36). 

Various terpene-derived materials are important in the formulation of fragrances and flavors. One example is the tricyclic furan shown below, which is commercially used under the trademark Ambrox. The synthetic sequences below have been developed to prepare related structures. Suggest reagents for each step in these sequences. 

A crystal structure is available for the compound with R = HC=C(CH2)2, and a mechanism was also proposed. On changing the reaction conditions (CH3CN, 82°C) and using Af-propionylimidazole, a tricyclic imidazo[l, 2 l,2]pyrrolo[2,3-6]furan was obtained in a diastereoselective spirocyclization reaction tl59],[157]... 

Tricyclic dithiine derivatives of tetrathiafulvalene (TTF) 32 have been prepared for their increased electropolymerization potential <2000CC1005>. The effect of different tricyclic heterocycles upon the redox properties of TTF analogues was explored, and showed that the furan derivative 33 had an unusual nonplanar conformation that allowed for the attainment of higher oxidation states at relatively low oxidation potentials <2004JMC2822>. 

Intramolecular Friedel-Crafts acylation of the furan ring of 403, which reacted at the 2-position, led to efficient formation of the linear 5 6 5 tricyclic system 404 in good yield (Equation 109) <1998JHC1371>. 

Arylidine-furan-2-ones 439 undergo [4+2] cycloaddition with maleic anhydride 440 to give the tricyclic adducts 441 (Equation 119) <1997CHE910>. 

Several examples reported in 2006 demonstrate that 2-substituted furans underwent spirocyclization at the 2-position. As illustrated in the scheme below, the reaction of a furan tethered at the 2-position to an iminium ion gave a spiro-2,5-dihydrofuran derivative as the sole diastereoisomer. This spirocyclization, which proceeded irrespective of the length of the carbon linker, was employed to construct the ABC tricyclic core of manzamine A <06OL27>. 

The psoralen ring system can intercalate within double-stranded DNA or RNA and induce the formation of adducts with adjacent thymine bases (Figure 11.15). The furan-side and pyrone-side of the tricyclic rings in psoralen both can form cycloaddition products with the 5,6-double bond of thymine residues, which results in crosslinks between the DNA strands with a PEG-biotin label sticking out. 

Cycloaddition reactions of furans are still widely used as key steps in the construction of complex molecules including natural products. As an example, the intramolecular Diels-Alder cycloaddition of 2-amido substituted furans provides a useful tool for the synthesis of fused, nitrogen-containing poly-heterocycles. Thus, thermolysis of 3-substituted amidofuran produces tricyclic indolinone 39 as a 2 1 mixture of diastereomers via amidofuran cycloaddition-rearrangement methodology, which serves as a key intermediate in the total synthesis of ( )-dendrobine, a major component of the Chinese ornamental orchid Dendrobium nobile . 

Similar to the Pd-catalyzed pyrrole and thiophene annulations, an intramolecular Heck reaction of substrate 91 resulted in benzofuran 92 [80], Such an approach has become a popular means of synthesizing fused furans. Muratake et al. exploited the intramolecular Heck cyclization to establish the tricyclic core structure en route to the synthesis of a furan analog of duocarmycin SA, a potent cytotoxic antibiotic [81]. Under Jeffery s phase-transfer catalysis conditions, substrate 93 was converted to tricyclic derivatives 94 and 95 as an inseparable mixture (ca. 4 1) of two double bond isomers. 

Ring closure to a fused furan was carried out by Kruglenko et al. <1998KGS258> the fused triazinone derivative 105 was treated with thionyl chloride under reflux conditions in chloroform to yield the tricyclic compound 106 in excellent yield. 

The class of 3-silyl-substituted reagents provides, upon addition with aldehydes, allylic silanes that offer many options for further derivatization. Oxidative processes are described in previous sections (see the sections on Preparation of 1,2-Diols and 1,4-Diols). If the appropriate silicon substituents are chosen, formal [3+2] cycloadditions with aldehydes can be promoted under Lewis acid catalysis. For example, the mismatched addition of the Z-3-propyl-3-benzhydryldimethyl allylsilane 183 to an a-benzyloxy aldehyde proceeds with low diastereofacial selectivity in favor of product 184 however, after protection of the secondary alcohol, an efficient [3+2] annulation provides the polysubsubstituted furan 185 in good yield and acceptable stereoselectivity (Scheme 24). ° The latter is brought forward to a tricyclic unit found in the antitumor natural product angelmicin B. 

Diels-Alder reactions with furans constitute a major class of cycloaddition reactions, which have been used for the preparation of a variety of new compounds. Some examples will be given in this section. A one-pot stereoselective synthesis of tricyclic -y-lactones was achieved via Diels-Alder reactions of 2-methoxyfuran with masked o-benzoquinones, which are in turn available from the corresponding 2-methoxyphenols <99CC713>. 

Addition of dichlorocarbene to benzofuran affords the tricyclic species (118) (63JOC577). The furan ring subsequently expands to a pyran, affording 2,3-dichlorochromene (119). This reaction is reminiscent of those shown by pyrrole and indole, which yield pyridine and quinoline derivatives, respectively. However, the product could not be purified and on hydrolytic work-up the dichromenyl ether (120) was isolated. 

Furan and maleic anhydride undeigo the Diels-Alder reaction to form the tricyclic 1 1 adduct, 7-oxabicydo [2.2. l]hept-5-ene-2,3-dicarboxylic anhydride (4) in excellent yield. Other strong dienophfl.es also add to furan (88). Although both endo and exo isomers are formed initially, the former rapidly isomerize to the latter in solution, even at room temperature. The existence of a charge-transfer complex in the system has been demonstrated (89,90). 

Double cyclopropanation of furans and pyrroles with aryl diazoacetates catalysed by Rh2(S-DOSP)4 have been reported to occur with opposite stereochemistry depending on the nature of the heterocycle.55 Better yields and ees are achieved for tricycles (69) derived from furan than for (68) derived from more bulky pyrroles. Monocyclo- propanation (with high yields and ees) is achieved on the furan ring of benzofuran, whereas double cyclopropanation of the indole is observed. 

Tricyclic structures (A, B, and C rings) 90 possessing the functionality and stereochemistry inherent in phorbol [63] and its analogues were constructed in one step by a high-pressure IRDAR. The nature of the 2-thioether substituent on the furan was critical for the success of the reaction a range of high-pressure conditions with the phenylthiofuran 89 (R1 = Me, R2 = Ph) led either to the recovery of starting material or decomposition (Scheme 26) [64],... 

In contrast to furans, photoinduced ring-degenerate rearrangements are largely represented in the thiophene series. Reported results have been often rationalized in terms of different competing mechanisms such as the zwitterion-tricyclic route, which takes advantage of the valence shell expansion of a sulfur atom and involves... 

The first structurally confirmed [2 + 4] adduct of a disilene and a 1,3-diene was compound 89, obtained from cyclopentadiene and 4174. The formation of the tricyclic compound 95 from furan and the cyclotrisilane 40 is probably initiated by a [2 + 4] cycloaddition of 41 to the five-membered ring to afford 94, which then undergoes a [2 + 1] addition at the newly formed double bond with the silylene 42 formed concomitantly in the photolysis of 40 (equation 16)74. 

---