3.4- Dihydro-2//-pyranes. formation

Aside from the ready preparation of some a,p-disubstituted cyclopentanones, the utility of the cyclopropanone hemiacetal approach has been illustrated by the total synthesis of the methyl ester of 11-deoxyprostaglandin E2 342 15). Towards this end, 1-trimethylsilylbutadiynylcyclopropanol 13, readily available from the cyclopropanone hemiacetal 3 (vide supra, Sect. 2.1, Eq. (6)) was successively treated with dihydro-pyran in CH2C12 in the presence of 10% mol. equiv. of PPTS 101). Desilylation by potassium fluoride in DMF 138), formation of the lithium salt with n-BuLi and condensation with hexanal gave the propargylic alcohol 339 in 64 % overall yield. The... 

Transformations of 5,6-dihydro-2//-pyrans 8 into the corresponding 3,4-dihydro-2//derivatives 9 under basic conditions (88KGS291 98TL2025), as well as the reverse conversion under irradiation [97H(46)451], have been explained by the intermediate formation of electron-delocalized heterocyclic systems, giving rise to two possible isomers. 

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. 

In the case of terminal alkynes having oxygenated functions in the linear chain (Scheme 10, route D), Martin, Padron, and coworkers found that homopropargylic alcohols reacted properly, yielding 2-substituted dihydropyrans as sole products, probably via a Prins-type cyclization. This cyclization provides a new approach toward 2-alkyM-halo-5,6-dihydro-2//-pyrans through a concomitant C-C and C-O bond formation (Scheme 21) [35]. 

Scheme 150).225 227 The pyran products predominate when the ratio of triphenylphosphine to palladium catalyst exceeds two whereas the linear oligomers are the major products when this ratio is close to unity. The suggested227 mechanism (Scheme 151) includes a step of insertion of C=0 into a C—Pd palladium-catalyzed reactions leading to the formation of pyranones (see Scheme 152)228 and piperidones (see Scheme 139 in Section V,A,2).211 It is useful to note that the 2,5-divinyltetrahydropyran derivative can be transformed catalytically by ruthenium trichloride into synthetically useful 3,4-dihydro-2//-pyran derivatives (Scheme 153).229... 

Shaking of rac-3,4-dihydro-6-methyl-2-(l-oxopropyl)-2/f-pyran with baker s yeast resulted in initial formation of racemic 6-hydroxy-2,7-nonanedione and then by kinetic resolution/ diastereoselective reduction in the production of (67 ,7S)-6,7-dihydroxy-2-nonanone (2) where both relative and absolute configuration had to be determined (see p 470)134. 

Enol ethers and enol acetates of cyclic 1,3-dicarbonyl compounds also afford mixtures of regioisomers on irradiation in the presence of allene, the preferential orientation of addition for enol ethers being mainly head-to-tail.9-11 Endocyclic enol ethers on the other hand, e.g. 2.3-dihydro-4//-pyran-4-ones 4, add regioselectively to allene with exclusive formation of head-to-head adducts.11... 

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... 

It has since been shown that the cycloaddition is catalyzed by transition metal salts (78JOC667). Although the yields are generally lower than irr the uncatalyzed reaction, this is outweighed by the advantages of shorter reaction times and a lower cyclization temperature. Illustrative examples of the formation of 2-alkoxy-3,4-dihydro-2//-pyrans are presented in Table 3, which includes a comparison of the two methods of synthesis. 

In a manifestation of the reaction shown above, quinoline rings have also been formed by the cycloaddition of /V-arylketenimines 543 with 3,4-dihydro-2//-pyran 455 under high-pressure conditions (Scheme 100) <2001H(55)1971>. The reaction is proposed to proceed via the initial formation of 544 by attack of the enol ether on the protonated ketenimine subsequent electrophilic aromatic substitution gives 545. Protonation of the enamine to give 546 is followed by elimination to produce 547. Protection of the alcohol with 455 gives 548. 

Treatment of 6-aryl derivatives of 4-substituted 2-oxo-27/-pyran-3-carbonitriles 500 (X = CN, Y = TV-1,2,3,4-tetrahydroisoquinolinyl) with ketones under basic conditions results in cleavage of the pyran ring and formation of new heterocyclic systems. Thus, tetrahydrothiopyran-4-one affords the 3,4-dihydro-1/7-2-benzothiopyran 501 (Scheme 185) <2005BML1341>. 

In studying the degradation of fructosylglycine in unbuffered and buffered aqueous solutions at 90 °C over 7 h, the pH being kept constant at 5, 6, 7, or 8, HMF was detected by Davidek et al.100 only at pH 5, whereas 2,3-dihydro-3,5-dihydroxy-6-methyl-4H-pyran-4-one was formed over the whole pH range studied. The phosphate buffer accelerated the formation of the latter compound at pH 5 and 6, but the formation of HMF was practically unaffected, suggesting that phosphate catalyses 2,3-enolisation at lower pH values. 

Steric hindrance can also reach a critical value during bond formation and might favor the formation of thermodynamically more stable product. Park et al. described the photocycloaddition of benzaldehyde to 2,2-diethoxy-3,4-dihydro-2H-pyran (123) as preferentially resulting in the exo-phenyl product 124 (Sch. 40) [124]. 

The electrophilic character of iodine in IOB is greatly increased by the addition of boron trifluoride, probably because of the in situ formation of the monomeric dipole Phl + OBF3 . Some cycloalkenes reacted with IOB.BF3 undergoing ring-contraction, for example cyclohexene gave formylcyclopentane (60%), and 3,4-dihydro-27/-pyran gave tetrahydrofurfural [8] ... 

Ru-catalysed enyne metathesis offers a short approach to chiral derivatives of 3-vinyl-5,6-dihydro-2//-pyrans. Some epimerisation can occur at the pyranyl C atom at elevated temperatures (Scheme 3) <02T5627>. The bispropargyloxynorbomene derivative 6 undergoes a cascade of metathesis reactions in the presence of alkenes and Grubbs catalyst incorporating an enyne-RCM that leads to fused cyclic dienes. A dienophile can be added to the reaction mixture, resulting in Diels-Alder reactions and the formation of functionalised polycyclic products <02TL1561>. 

The other factor that may determine the type of cell death is the chemical structure of inducing agents [14]. We have recently found that u,(>-unsaluraled ketones such as 4,4-dimethyl-2-cyclopenten-l-one, a-methy-lene-y-butyrolactone, 5,6-dihydro-2H-pyran-2-one [15], codeinone [16], and morphinone [17] and a-hydroxylketones such as 3,3,3-trifluoro-2-hydroxy-1-phenyl-1-propanone induced caspase-independent cell death [18], induced vacuolization or autophagosome formation engulfing organelles, but without induction of apoptosis markers. 

In the photo-oxygenation of enol ethers, where the ene reaction and [2 + 2]-cycloaddition compete, polar solvents favour cycloaddition whereas nonpolar solvents favour ene product formation [681, 683-685]. For example, 2,3-dihydro-4-methyl-4/f-pyran reacts with singlet oxygen to yield both a 1,2-dioxetane and an allylic hydro-... 

Since the disclosures that the thermal dimerizations of acrolein and methyl vinyl ketone provide the 3,4-dihydro-2//-pyrans (1, 2) derived from 4ir and 2Tt participation of the a,3-unsaturated carbonyl compound in a Diels-Alder reaction, an extensive series of related observations have been detailed. This work has been the subject of several comprehensive reviews - - including the Desimoni and Tacco-ni extensive tabular compilation of work through 1974. Consequently, the prior reviews should be consulted for thorough treatments of the mechanism, scope, and applications of the [4 + 2] cycloaddition reactions of a,3-unsaturated carbonyl compounds. The [4 + 2] cycloaddition reactions of 1-oxa-1,3-butadienes with their 4-it participation in the Diels-Alder reaction exhibit predictable regioselectivity with the preferential or exclusive formation of 2-substituted 3,4-dihydro-2W-pyrans (equation 1). The exceptions to the predicted regioselectivity that have been observed involve the poorly matched [4 + 2] cycloaddition reaction of an electron-deficient l-oxa-l,3-butadiene with an electron-deficient dienophile, e.g. methyl crotonate or methacrolein. - Rigorous or simplified theoretical treatments of the [4 + 2] cycloaddition reaction of 1-oxa-1,3-butadienes predict the preferential formation of 2-substituted 3,4-dihy-dro-2f/-pyrans and accommodate the preferred endo approach of the reactants in which the carbon-carbon bond formation is more advanced than carbon-oxygen bond formation, i.e. a concerted but nonsynchronous [4 + 2] cycloaddition reaction. ... 

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