Pyrans => alkenes

Cyclization of hydroxyalkenes to furanes and pyranes Alkenes suitably substituted by a hydroxyl group undergo cyclization and carbonylation in the presence of PdCl,/ CuCI to pyranes and/or furanes. The preference for five- or six-membered rings depends mainly on the geometry of the alkenc (E)-alkcnes cyclize mainly to pyranes and (Z)-alkenes cyclize mainly to furanes. 

A simple approach for the formation of 2-substituted 3,4-dihydro-2H-pyrans, which are useful precursors for natural products such as optically active carbohydrates, is the catalytic enantioselective cycloaddition reaction of a,/ -unsaturated carbonyl compounds with electron-rich alkenes. This is an inverse electron-demand cycloaddition reaction which is controlled by a dominant interaction between the LUMO of the 1-oxa-1,3-butadiene and the HOMO of the alkene (Scheme 4.2, right). This is usually a concerted non-synchronous reaction with retention of the configuration of the die-nophile and results in normally high regioselectivity, which in the presence of Lewis acids is improved and, furthermore, also increases the reaction rate. 

More recently, further developments have shown that the reaction outlined in Scheme 4.33 can also proceed for other alkenes, such as silyl-enol ethers of acetophenone [48 b], which gives the endo diastereomer in up to 99% ee. It was also shown that / -ethyl-/ -methyl-substituted acyl phosphonate also can undergo a dia-stereo- and enantioselective cycloaddition reaction with ethyl vinyl ether catalyzed by the chiral Ph-BOX-copper(ll) catalyst. The preparative use of the cycloaddition reaction was demonstrated by performing reactions on the gram scale and showing that no special measures are required for the reaction and that the dihydro-pyrans can be obtained in high yield and with very high diastereo- and enantioselective excess. 

Inverse electron-demand Diels-Alder reaction of (E)-2-oxo-l-phenylsulfo-nyl-3-alkenes 81 with enolethers, catalyzed by a chiral titanium-based catalyst, afforded substituted dihydro pyranes (Equation 3.27) in excellent yields and with moderate to high levels of enantioselection [81]. The enantioselectivity is dependent on the bulkiness of the Ri group of the dienophile, and the best result was obtained when Ri was an isopropyl group. Better reaction yields and enantioselectivity [82, 83] were attained in the synthesis of substituted chiral pyranes by cycloaddition of heterodienes 82 with cyclic and acyclic enolethers, catalyzed by C2-symmetric chiral Cu(II) complexes 83 (Scheme 3.16). 

Enynes 71 react with aldehydes 61 in the presence of the [Ni(COD)J/SIPr catalytic system to afford two distinct products 72 and 73 (Scheme 5.20) [20b], The enone 72 is derived from aldehyde addition with the alkyne moiety while the adduct 73 arises from the aldehyde addition with the alkene moiety. The product distribution is dependent on the substituent on either the alkyne or alkene moieties. The reaction between 71 and ketones 74 led to the unprecedented formation of pyrans 75 (Scheme 5.20). The reaction showed to be highly regioselective in aU the cases, the carbonyl carbon was bound to the olefin. 

An interesting feature of the cyclization of y, -unsaturated alcohols is the marked effect on product isomer distribution by the nature of substituents remote from the double bond (cf. 42 and Scheme 59).98 Complete stereospecificity is observed for the phenyl derivative 42a in contrast to 42b and c, and the isomer ratio is reversed for 42d. The suggested mechanism98 is shown in Scheme 60 the trisubstituted alkene (45) is mainly converted into a pyran (46) rather than a tetrahydrofuran derivative (Scheme 61). 

A pyran ring is formed in the intramolecular Diels-Alder cycloaddition of alkene-tethered enantiopure (lS,2R)-l,2-dihydroxycyclohexa-3,5-diene-l-carboxylic acid derivatives (derived from the biodihydroxylation of benzoic acid). For the three cases illustrated in Scheme 6.246, Mihovilovic and colleagues found that moderate to high yields of the desired cycloadducts could be obtained by exposing a solution of the precursor to microwave irradiation at 135-210 °C for extended periods of time... 

The conversion of anomerically linked enol ethers 29 into either the cis- or trans-substituted pyranyl ketones with high diastereoselectivity and yield involves a Lewis acid-promoted O —> C rearrangement (Scheme 19) <00JCS(P1)2385>. Under similar conditions, homoallylic ethers 30 ring open and the oxonium ions then recyclise to new pyran derivatives 31. Whilst the product is a mixture of alkene isomers, catalytic hydrogenation occurs with excellent diastereoselectivity (Scheme 20) <00JCS(P1)1829>. 

The high levels of enantioselectivity obtained in the asymmetric catalytic carbomagnesa-tion reactions (Tables 6.1 and 6.2) imply an organized (ebthi)Zr—alkene complex interaction with the heterocyclic alkene substrates. When chiral unsaturated pyrans or furans are employed, the resident center of asymmetry may induce differential rates of reaction, such that after -50 % conversion one enantiomer of the chiral alkene can be recovered in high enantiomeric purity. As an example, molecular models indicate that with a 2-substituted pyran, as shown in Fig. 6.2, the mode of addition labeled as I should be significantly favored over II or III, where unfavorable steric interactions between the (ebthi)Zr complex and the olefmic substrate would lead to significant catalyst—substrate complex destabilization. 

Zirconocene-catalyzed kinetic resolution of dihydrofurans is also possible, as illustrated in Scheme 6.8 [18]. Unlike their six-membered ring counterparts, both of the heterocycle enantiomers react readily, albeit through distinctly different reaction pathways, to afford — with high diastereomeric and enantiomeric purities — constitutional isomers that are readily separable (the first example of parallel kinetic resolution involving an organome-tallic agent). A plausible reason for the difference in the reactivity pattern of pyrans and furans is that, in the latter class of compounds, both olefmic carbons are adjacent to a C—O bond C—Zr bond formation can take place at either end of the C—C 7T-system. The furan substrate and the (ebthi)Zr-alkene complex (R)-3 interact such that unfavorable... 

Behavioral observations of male white-tailed deer indicate that urine could play a role in olfactory communication in this animal [131]. To extend the knowledge of the urinary volatiles of the white-tailed deer and to investigate the possibility that vaginal mucus could also carry semiochemical information, Jemiolo et al. [132] studied the qualitative and concentration changes in the profiles of the volatiles present in these excretions. Forty-four volatiles were found in the mucus and 63 in female urine. The volatiles common to both vaginal mucus and urine included alcohols, aldehydes, furans, ketones, alkanes, and alkenes. Aromatic hydrocarbons were found only in the mucus, whereas pyrans, amines, esters and phenols were found only in the urine. Both estrous mucus and estrous urine could be identified by the presence of specific compounds that were not present in mid-cycle samples. Numerous compounds exhibited dependency on ovarian hormones. 

A solid-phase synthesis of furo[3,2-3]pyran derivatives utilizing highly functionalized sugar templates has been reported <2003JOC9406>. After incorporation of alkenes within the sugar template, such as compound 95, the solid support is introduced via formation of the acid amide. This immobilized system then allows a ruthenium-catalyzed ring-closing metathesis that leads to the formation of the fused oxacycles. 

Pyranone 127 reacts with alkenes in the presence of cerium ammonium nitrate via a cyclization reaction that leads to the formation of furo[2,3-3]- and furo[3,2-f]-pyranones in moderate yields (Equation 60). This reaction can be extended to the synthesis of furoquinolinones <1999H(51)2881>. Dihydropyran 128, with either / -diketones or /3-keto esters, undergoes cycloaddition reactions promoted by ceric ammonium nitrate to generate furo[2,3-3]pyrans in good yields (Equation 61) <1996T12495>. 

Furopyranopyrandiones have been prepared by the cerium(iv) ammonium nitrate-mediated reaction of 4-hydroxy-277,577-pyrano[4,3- ]pyran-2,5-diones with alkenes (Scheme 14) <2003H(60)939>. 

Pyrano[2,3- ]-l,2,4-trioxines 260a-c arise in low yield from the reaction of the appropriate alkene, 3,4-dihydro-277-pyran 258, with singlet oxygen in the presence of methylene blue (MB), followed by condensation of the intermediate oxetane 259 with acetaldehyde or acetone as appropriate (Scheme 43) <1997H(46)451>. 

Hydrogenation of the triple bond in 195 to a cis double-bond, followed by acid-catalyzed cyclization of the alkene, leads to 6-substi-tuted 2-alkoxy-5,6-dihydro-2//-pyrans (196). This method was used by H. Newman86 for the preparation of 2-ethoxy-5,6-dihydro-6-methyl-2H-pyran (196, R1 = Et, R = Me). 

Six-membered oxaenoncs [e.g., 5,6-dihydro-2i/-pyran-2-one,109, 2,2-dimethyl-l,3-dioxin-4-one,110-112 2,2-dimethyl-2/f-furo[3,4- ]pyran-4,7(3//,5//)-dione113] also give cyclobutanes on irradiation in the presence of alkenes. The corresponding six-membered thiaenones usually deactivate via ZjE isomerization.114... 

The extensive delocalization and aromatic character of pyridones, pyrones, etc. are shown by their chemical shift and coupling constant values (Table 8). By contrast, pyrans and thiins show chemical shifts characteristic of alkenic systems (Table 9). For these and for rings containing only a single endocyclic bond (Table 10), H NMR spectroscopy offers a most useful tool for structure determination. 

Reactions of unsaturated esters with electron-rich alkenes have been reported to yield only cyclobutane derivatives. However, NMR examination of the products has indicated the formation of substituted 3,4-dihydro-2H-pyrans. The most informative feature of the spectra is the C-2 proton coupling constants of ca. 3 Hz with the two different protons at... 

The chemical shifts of H-3 and H-4 in coumarin (19) are similar to those in pyran-2-one (Figure 4). The values are closely related to the shifts of the a and /3 protons of o-coumaric acid (56), implying that the heteroring has little or no aromatic character (62pia(A)(56)71). The signal for H-3 appears at higher field than that from H-4 and distinction between 3-and 4-substituted isomers is usually possible. Coupling between the alkenic protons is typical of a m-alkene (/3t4 = 9.8 Hz) and the pair of doublets is a characteristic feature of the spectra of coumarins. 

Analysis of the far IR-spectra of 3,4-dihydro-2//- pyran (13) (72JCP(57)2572> and 5,6-dihydro-2/f- pyran (14) (81JST(71)97> indicates that for both molecules the most stable conformation is a half-chair form. The barrier to planarity is greater for the former compound. These preferred structures are in accord with the half-chair conformation established for cyclohexene and its derivatives. The conformational mobility of cyclohexene is greater than that of the 3,4-dihydropyran. The increased stabilization of the pyran has been attributed to delocalization of the v- electrons of the alkenic carbon atoms and the oxygen lone-pairs (69TL4713). 

Mono- and bi-cyclic pyran-4-ones undergo photoaddition with unsaturated organic compounds (73BCJ690,66TL1419). When chromone is irradiated with an alkene or alkyne, addition... 

Dihydropyrans and tetrahydropyrans add on alkenes when irradiated but some of the products are unstable. 3,3-Dimethylpyran-2,4-dione (664) and an unsymmetrical diene such as 2-methylprop-l-ene (665) give regiospecifically a 1 1 mixture of cis- and frans-fused pyran-4-one (666) (73T1317). Tetrahydropyran (667) does not undergo photoaddition unless a sensitizer such as benzophenone is present, but then it reacts with diethyl maleate (668) (67T3193). 

In the presence of freeze-dried potassium fluoride, perfluoro-2-methylpent-2-ene reacts with activated methylene compounds to yield pyrans (81MI22400). The fluoride ion abstracts a proton from the methylene group and subsequent condensation of the carbanion with the perfluoroalkene affords a dienone (19) which ring closes to the pyran (20 Scheme 3). In the case of pentane-2,4-dione a divinyl ether (21) is also formed. This product is considered to arise from reaction of the alkene at the oxygen of the enolate ion. 

Two variations are worthy of mention. The alkene may be generated in situ, as for instance in the formation of the pyran from 3-bromopentane-2,4-dione. Secondly, the use of cyclic molecules as the activated methylene component leads to fused pyrans (146) and (147) from TCNE and ethyl cyanoacetate, respectively (73CB914). 

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