Bicyclic dihydrofuran

The stereochemical outcome of this photoaddition can be rationalised by the cyclopentenone adding on to the less hindered exo-face of the bicyclic dihydrofuran 7, as shown in Figure 6.1. 

Pirrung [153] has described the synthesis of ( )-pongomol 66 via the rhodium(II)-mediated reaction of the diazacyclohexane dione 67, to afford the fused bicyclic ketone 68 (Scheme 19.8). Moreover, this group [154] also detailed a similar approach in their synthesis of ( )-isoeuparin 69 (Scheme 19.9). Pirrung and Lee [155] expanded their rhodium(II)-mediated dihydrofuran cycloaddition strategy, for the conversion of the... 

An intramolecular substitution of trimethylamine fix>m 17 gave a bicyclic oxetane 18 in a diastereoselective process <98MI2185>. A [2+2]cycloaddition of 2,2,4,5-tetrasubstituted 2,3-dihydrofuran to aryl aldehydes gave the bicyclic oxetane 19 <98JCS(P1)3261>. 2,2-Disubstituted-3-bromooxetane was obtained by a 4-endo-tcig cyclization process of 3,3 -disubstituted allyl alcohol in the presence of bis(collidine)bromine hexafluorophosphate <99JOC81>. 

When a high-yield synthesis of the enantio- and diastereomerically pure mono-cyclic 2,3-dihydrofurans 44 from the vinyl sulfoximines 39 had been developed, the synthesis ofbicyclic 2,3-dihydrofurans of type 50 (Scheme 1.3.19) was investigated. Since a number of tetrahydrofuranoid natural products contain a fused bicyclic ring skeleton, the attainment ofbicyclic 2,3-dihydrofurans of the 50 type would also be desirable. 

The methylation of sulfoximines 45 with Me30BF4 proceeded readily and gave the corresponding cyclic aminosulfoxonium salts 46 in quantitative yields. Upon treatment with LiN(H)t-Bu first at-78 °C and then at room temperature, salts 46 delivered the enantio- and diastereomerically pure bicyclic 2,3-dihydrofurans 50 cleanly in high overall yields. It is proposed that the reactions of the aminosulfoxonium salts 40 and 46 with the lithium amide at low temperatures afford the vinyl aminosulfoxonium ylides 41 and 47, respectively. These alkylidene carbenoids eliminate sulfinamide 35 at higher temperatures with formation of the alkylidene carbenes 42 and 48, respectively. Subsequently, the alkylidene... 

Scheme 1.3.19 Asymmetric synthesis of bicyclic 2,3-dihydrofurans via O—Si bond insertion of alkylidene carbenes.

The formation of cyclopropane derivatives by photolysis of diazoalkanes in the presence of alkenes is believed to occur by photolytic decomposition of the diazoalkane to yield the carbene, followed by addition of this carbene to the alkene. Cycloaddition of this type has been reported in furan, dihydrofuran, and thiophene.198 Thus, photolysis of ethyl diazoacetate in thiophene yields the bicyclic sulfur heterocycle (215). Alternatively, photolysis of 3-diazo-l-methyl-oxindole (216) in cyclohexene leads to the formation of two isomers which are thought to have the spirocyclopropyl structure (217) photolysis in ethanol yields 3-ethoxy-1-methyloxindole.194... 

An /V-allylaminium cation radical undergoes an addition-cyclization reaction with vinyl ethers in the presence of t-BuSH to give 3-alkoxy-4-methylpyrrolidines 72 (Scheme 23) in fair to good yields (90TL1675). In addition to EVE, 2,3-dihydrofuran and 3,4-dihydro-(2//)pyran also undergo reactions to give bicycles 73 and 74, respectively, in reasonable yield. 

In contrast to the diastereoselectivity of the 2,3-dihydrofuran photocycloaddition, the photocycloaddition of furan with aromatic as well as aliphatic aldehydes proceeded with unusually high exo-diastereo-selectivity to give the bicyclic oxetanes 119 in good yield (Sch. 39) [123]. The diastereoselectivity of reaction of furan with acetaldehyde and benzaldehyde (iexo/endo) were 19 1 and 212 1, respectively. 

The synthesis of dihydrofuran derivatives such as 177 has been performed to explore scope and limitations of the Lewis acid promoted hydroxyalkylation of siloxycyclopropanes. Table 6 shows that aromatic as well as aliphatic ketones can efficiently be incorporated. Enolization of ketones does not occur and a 1-methyl group at the cyclopropane is no obstacle for the reaction, which now binds the carbonyl compound to a quartemary center with surprisingly high efficiency (entry 5). Albeit there are some restrictions with regard to the substitution pattern of the cyclopropanes, bicyclic siloxycyclopropanes also give good yields (e.g. entry 6 and Eq. 76). Further examples of the tetrahydrofuran synthesis from intermediate y-lactols with... 

Adduct 180 can be transformed to various furan derivatives (Scheme 9)61). Dehydration is accompanied by cis/trans isomerization giving tra/w-dihydrofuran 186, and oxidation to ketone 187 followed by condensation provides the trisubstituted furan 188. Cyano and allyl trimethylsilane, respectively, lead to tetrahydrofuran derivatives 189 and 190 with high stereoselection, which carry new substituents suitable for further manipulation. These reactions work equally well for the ketone adduct 176 and a bicyclic y-lactol affording 191-193 93). 

Reaction of functionalized bicyclic compound with DDQ provided the tricyclic core of phomactin A. This product with a dihydrofuran subunit, was extremely unstable and dehydrated readily to form the corresponding furan <02OL2413>. 

Reactions of furans, dihydrofurans, tetrahydrofurans and benzo[f]furans have been reviewed <2007PHC187>. Derivatives of new furan skeletons were synthesized from bicyclic azo compounds and nitriles in the presence of SbCls or AICI3. An example is shown in Scheme 86 <2007S33>. 

A BINAP-Pd complex catalyzes a highly enantioselective C-C bond formation between an aryl triflate and 2,3-dihydrofuran (eq 22). The intramolecular version of the reaction using an alkenyl iodide in the presence of PdCl2[(/J)-BINAP] and Silver(I) Phosphate allows enantioselective formation of a bicyclic ring system (eq 23). ... 

Interesting compounds th bicyclic P-lactams (also those cyclic ethers, cyclic siloxj spiroannulated dihydrofuran organized by Cu(I). ... 

Interesting compounds that have been acquired from the metathesis process include bicyclic P-lactams (also those comprising a diene unit by the enyne metathesis ), a-stannyl cyclic ethers, cyclic siloxanes which can be opened to afford (Z)-alkenediols, spiroannulated dihydrofurans and dihydropyrans, and [2]catenanes from precursors organized by Cu(I). ... 

Similar reactions using dihydropyrans and dihydrofurans furnish cyclobutanes or alkenol products upon hydrolysis (Scheme 18). As with the previous applications, zirconacyclic intermediates are implicated. Differences in stereochemistry in the observed products versus the open chain vinyl substrates are thought to arise from geometric restrictions imposed by the bicyclic intermediates. 

The enantioselective hetero-Diels-Alder reactions of a,p-unsaturated acylphosphonates with enol ethers catalyzed by Cu(II)bzT(oxazoline) complexes have been investigated in depth. It was found that Cu(II)bA(oxazoline) complexes activate a,p-unsaturated acylphosphonates to the extent that they undergo facile cycloaddition reactions at low temperature with electron-rich alkenes. For example, dimethyl ( )-l-oxo-2-butenylphosphonate reacts with ethyl vinyl ether in the presence of Cu[(S,5)-t-Bu-box] (OTf)2 complex (10 mol% catalyst) to generate the cycloadduct in 89% yield (Scheme 7.86) with exceptional stereoselectivity (endo/exo = 99/1, 99% ee). Cyclic enol ethers also undergo stereoselective reactions with dimethyl ( )-l-oxo-2-butenylphosphonate. It specifically reacts with 2,3-dihydrofuran in the presence of Cu[(5,5)-t-Bu-box] (OTf)2 to deliver the bicyclic enolphosphonate. Of particular merit is the fact that a large variety of p.y-unsaturated acylphosphonates may be tolerated with no loss in selectivity for the derived cycloadducts. ... 

This TiCU-promoted allene cycloaddition has also been extended to the synthesis of five-membered ring heterocycles.In this case, increasing the steric shielding about the silicon atom seems to improve the cyclization process by suppressing the unproductive desilylative alkylation. For example, 1,3-di-methyl(r-butyldimethylsilyl)allene (39) reacts smoothly with cyclohexanecarbaldehyde to give in high yield the dihydrofuran predominantly as one stereoisomer (equation 31). Similar reaction with aniV-acyl-iminium ion precursor (40) produces the pyrrolizidine system as a mixture of bicyclic isomers (equation... 

Benzylideneanilines have been added across 2,3-dihydrofurans to produce bicyclic azetidines regio- and stereoselectively a zwitterionic mechanism is proposed. An extensive range of reaction parameters have been calculated for the Mannich reaction of benzoxazole with formaldehyde/dimethylamine. A molybdenum bis(imide) has been used to catalyse C=N bond formation in imine-imine metathesis reactions of synthetic interest the approach has been extended to alkylidene-imine, imide-imine, and imide-imide metatheses. 1-Substituted 1-phenyl-... 

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