Dihydro-2H-pyran

In an intramolecular variant of this reaction, the use of sterically defined alkenes permits a stereoselective construction of stereogenic centers in six-membered heterocycles, as demonstrated in the following example for the key building block 52 of a yohimbine synthesis [18]  

4-Dihydro-2H-pyran and 5,6-dihydro-2H-pyran can be considered as oxa-analogs of 0 cyclohexene  

4-Dihydro-2H-pyran has the spectroscopic and structural characteristics of a cyclic enolic ether, as is shown by its NMR and IR spectroscopic data  

Examination of Raman spectra shows that at room temperature 3,4-dihydro-2H-pyran exists predominantly in a half hair conformation with a twist-angle of 23°. According to H NMR spectra the conformers of 2-alkoxy- and 2-aryloxy-3,4-dihydro-2H-pyrans are in equilibrium. The conformer with the 2-OR in an axial position predominates due to an anomeric effect (see p. 317)  

4-Dihydro-2H-pyrans show the reactivity of systems with electron-rich double bonds. 

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Intermediates. 3,4-Dihydro-2H-pyran [110-87-2] is prepared by a ring-expanding dehydration of tetrahydrofurfuryl alcohol. It is used as a protecting agent for hydroxyl compounds and as an intermediate. 2-Methylfuran is a chemical intermediate for 5-methylfurfural [620-02-0] (151) and... 

Similar cycloaddition reactions were observed with methyl vinyl sulfone (48) and )3-nitrostyrene (48,51). Methyl vinyl ketone, on the other hand, is reported to give dihydropyrans as the initial products (50,52,53). Thus (16) on reaction with methyl vinyl ketone at room temperature for 12 hr gave a 60% yield of 2-dimethylamino-3,3,6-trimethyl-3,4-dihydro-2H-pyran (59). 

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. 

Aus 2-Oxo-5,6-dimethyl-3,4-dihydro-2H-pyran erhalt man so 5-Oxo-4-methyl-hexa-nol (Kp10 104—106°) in 42%iger Ausbeute1. 

In connection with studies on the ring-opening polymerization of cyclic acetals, we have undertaken investigations on the polymerization of bicyclic acetals, bicyclic oxalactone, and bicyclic oxalactam, which yield polysaccharide analogs, macrocyclic oligoesters, and a hydrophilic polyamide, respectively, some of which can be expected to be useful as novel speciality polymers. The monomers employed in the studies were prepared via synthetic routes presented in Scheme 1, starting from 3,4-dihydro-2H-pyran-2-carbaldehyde (acrolein dimer) I. 

Polymerization of 6,8-dioxabicyclo[3.2.1]octane, 2, has been most extensively studied among bicyclic acetals. This monomer is readily prepared from 3,4-dihydro-2H-pyran-2-carbaldehyde 1 by reduction with sodium borohydride followed by add-... 

A new class of bicyclic oxalactam, 8-oxa-6-azabicyclo[3.2.1]octan-7-one 61 was synthesized by intramolecular cyclization of 3,4-dihydro-2H-pyran- 2-carboxamide 62 using p-toluenesulfonic acid as a catalyst in an equivalent mixture of DMF and benzene at 100 °C for 4 hours57, S8. Corresponding conversion of 3-cyclohexane carboxamide 63 to bicyclic lactam 64 has never been accomplished54. ... 

Synthesis of highly functionalized 3,4-dihydro-2H-pyrans by high-pressure Lewis-acid-catalyzed cycloaddition of enol ethers and a,/i-unsaturated aldehydes [83]... 

Pyrimidinyl palladium reagents, prepared in situ from mercuric or iodo derivatives, react with 3,4-dihydro-2H-pyran to form isomeric products containing a dihydropyranyl group attached to C-5 of the substituted uracil... 

The experimental procedure described is essentially one reported by Ziegler and Wilms 8 as subsequently modified,9 except that the glutaraldehyde is prepared from 2-ethoxy-3,4-dihydro-2H-pyran instead of cyclopentene ozonide 8 or pyridine via dihydropyridine and glutaraldehyde dioxime.9 Essentially these procedures have also been reported briefly by other investigators.10... 

As these acetals could be converted into the 4,6-O-ethylidene derivatives on treatment with acid, it was reasoned that use of a cyclic vinyl ether, namely, 3,4-dihydro-2H-pyran, might prevent this second process, thus leading to a more useful method of selective acetalation.338 An equimolar reaction with methyl a-D-glu-copyranoside for 4 days in N,N-dimethylformamide led to utilization of 88% of the glycoside, and the 6-(tetrahydropyran-2-yl) ether constituted —85% of the crude reaction-product. In contrast to the steric control apparent in this instance, reaction of 3,4-dihydro-2H-pyran with the axial and equatorial hydroxyl groups in dl-1,4,5,6-tetra-O-acetyl-mi/o-inositol was completely unselective,339 a fact that has been rationalized310 in terms of the probable mechanism of these reactions. 

Ballantyne, B., D.E. Dodd, I.M. Pritts, D.J. Nachreiner, and E.H. Fowler. 1989. Acute vapour inhalation toxicity of acrolein and its influence as a trace contaminant in 2-methyoxy-3,4-dihydro-2H-pyran. Human Toxicol. 8 229-235. 

Merrifield resin (1 % crosslinked) was employed as the solid support. The problem of oligomerization was prevented by protection of the hydroxyl of 38 as a THP ether by treatment with 3,4-dihydro-2H-pyran (DHP) in the presence of pyridinium /7-toluenesulfonate (PPTS) to give 46. Immobilized 46 was successfully coupled with 24 to give disaccharide 47. The THP group of 47 was easily removed by treatment with acetic acid/water to yield 45. 

Scheme 6.76 Generation of l-oxa-2,3-cyclohexadiene (351) from 5-bromo-3,4-dihydro-2H-pyran (376) and trapping products of351 obtained from furan, 2,3-dimethyl-1,3-butadiene, 1,1-diphenyl-ethylene, ( )-l-phenylpropene, ( )-2-butene, (Z)-2-butene and tert-butyl alcohol , according to Schlosserand co-workers.

Scheme 6.80 Reactions of 5-bromo-3,4-dihydro-2H-pyran (376) with complex bases composed of NaNH2 or NaNH2-NaOtBu and enolates of ketones, accordingto Caub re and co-workers.

Saalfrank, Hoffmann and co-workers performed a number of reactions with tetra-alkoxyallenes such as 196 (Scheme 8.47) [1, 41, 105, 114—116] and demonstrated that this class of donor-substituted allenes can serve as a 1,3-dianion equivalent of malonic acid. Treatment of 196 with cyclopropyldicarboxylic acid dichloride 197 produces 2,4-dioxo-3,4-dihydro-2H-pyran 198 through release of two molecules of ethyl chloride [115]. Similarily, the reaction of this allene 196 with oxalyl chloride gives 3-chloromalonic acid anhydride derivative 199. This intermediate is a reactive dieno-phile which accepts 2,3-dimethyl-l,3-butadiene in a subsequent [4+2] cycloaddition to afford cycloadduct 200 in good yield [116]. 

Inverse type hetero-Diels-Alder reactions between p-acyloxy-a-phenylthio substituted a, p-unsaturated cabonyl compounds as 1-oxa-1,3-dienes, enol ethers, a-alkoxy acrylates, and styrenes, respectively, as hetero-dienophiles result in an efficient one step synthesis of highly functionalized 3,4-dihydro-2H-pyrans (hex-4-enopyranosides). These compounds are diastereospecifically transformed into deoxy and amino-deoxy sugars such as the antibiotic ramulosin, in pyridines having a variety of electron donating substituents, in the important 3-deoxy-2-gly-culosonates, in precursors for macrolide synthesis, and in C.-aryl-glucopyranosides. 

Aiming at the pyranose form of sugars, normal type hetero-Diels-Alder reactions were extensively used for the synthesis of functionally substituted dihydropyran and tetrahydropyran systems (5-10) (see routes A - D in the general Scheme 1) which are also important targets in the "Chiron approach" to natural product syntheses (2.) Hetero-Diels-Alder reactions with inverse electron demand such as a, p-unsaturated carbonyl compounds (l-oxa-1,3-dienes) as heterodienes and enol ethers as hetero-dienophiles, are an attractive route for the synthesis of 3,4-dihydro-2H-pyrans (11). 

In 2007, another departure from carbonyl-type activation was marked by Kotke and Schreiner in the organocatalytic tetrahydropyran and 2-methoxypropene protection of alcohols, phenols, and other ROH substrates [118, 145], These derivatives offered a further synthetically useful acid-free contribution to protective group chemistry [146]. The 9-catalyzed tetrahydropyranylation with 3,4-dihydro-2H-pyran (DHP) as reactant and solvent was described to be applicable to a broad spectrum of hydroxy functionalities and furnished the corresponding tetrahydro-pyranyl-substituted ethers, that is, mixed acetals, at mild conditions and with good to excellent yields. Primary and secondary alcohols can be THP-protected to afford 1-8 at room temperature and at loadings ranging from 0.001 to 1.0mol% thiourea... 

Disubstituted dihydropyrans are produced with high u/iri-selectivity when 2-phenyl-4-(4-tolylsulfonyl)-3,4-dihydro-2H -pyrans ate treated with Al-based Lewis acids <99SL132>. Tetraenes 10, derived from dienes via their epoxides, undergo a double RCM reaction under Ru-catalysis to yield polycyclic ethers 11 in which the dihydropyran units can be joined by a variable number of carbon atoms <99JOC3354>. Continued work on the use of dispiroketals in synthesis has led to an improved route to the enantiomers of bi(dihydropyrans) 12 <99JCS(P1)1639>. 

Although many organic chemists still use 3,4-dihydro-2H-pyran [214,215] for the protection of OH groups, protection with ethyl vinyl ether has distinct advantages. Ethyl vinyl ether [216] is much cheaper than the cyclic ether, but chemists working in a university will perhaps find the advantage of the easier protection and deprotection more important Furthermore, H NMR-spectroscopic analysis of the adducts from ethyl vinyl ether in many cases will be easier. 

Ein Spezialfall ist die 2-Tetrahydropyranyl-Gruppe, deren Einfuhrung an 4(5)-Nitro-imidazolen mit 3,4-Dihydro-2H-pyran unter Saurekatalyse gelingt [4(5)-Nitro-l-(2-tetrahydropyranyl)-imidazol 742. 

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