Diene pyrans, dihydro

Production of Acrolein Dimer. Acting as both the diene and dienoplule, acrolein undergoes a Diels-Alder reaction with itself to produce acrolein dimer, 3,4-dihydro-2-formyl-2id-pyran, CgHg02 [100-73-2], At room temperature the rate of dimerization is very slow. However, at elevated temperatures and pressures the dimer may be produced in single-pass yields of 33% with selectivities greater than 95%. 

Examples of the use of heterodienophiles under the action of microwave irradiation are not common. Soufiaoui [84] and Garrigues [37] used carbonyl compounds as die-nophiles. The first example employed solvent-free conditions the second is an example of the use of graphite as a susceptor. Cycloaddition of a carbonyl compound provided a 5,6-dihydro-2H-pyran derivative. These types of reaction proceed poorly with aliphatic and aromatic aldehydes and ketones unless highly reactive dienes and/or Lewis acid catalysts are used. Reaction of 2,3-dimethyl-l,3-butadiene (31) with ethyl glyoxylate (112) occurred in 75% yield in 20 min under the action of microwave irradiation. When conventional heating is used it is necessary to heat the mixture at 150 °C for 4 h in a sealed tube to obtain a satisfactory yield (Scheme 9.33). 

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). 

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>. 

Diels-Alder reactions. Diels-Alder reactions between this diene and carbonyl compounds are possible under high pressure (15-25 kbar) and provide a route to 5,6-dihydro-2//-pyranes (2).1 Example ... 

New possibilities in hetero-Diels-Alder condensation have been opened by the introduction of highly active l-methoxy-3-trimethylsilyloxy-, 4-benzoyIoxy-l-methoxy-3-trimethylsilyloxy-, and 2-acetoxy-l-alkoxy-3-trimethylsilyloxy-l,3-butadienes ( Danishefsky dienes, 5). These compounds readily react under atmospheric pressure, in the presence of Lewis acids, with normal aldehydes (e.g., acetaldehyde, benzaldehyde, furfural) to furnish 2,3-disubstituted or 2,3,5-trisubstituted derivatives of 2,3-dihydro-4H-pyran-4-one 7 capable of readily functionalizing to sugars (Scheme 5) [26]. This approach... 

In Section III, Danishefsky s methodology is illustrated by the synthesis of the basic compound 2,3-dihydro-4//-pyran-4-one, and 1-menthyl 2,3,6-tri-0-acetyl-4-deoxy-L-glucopyranoside. In this last example, high enantiomeric purity was achieved owing to the matched interaction between the catalyst [(+)-Eu(hfc)3] and the diene containing a chiral (1-menthyl) moiety. 

Methyl 2-methoxy-5,6-dihydro-2H-pyran-6-carboxylate (2 R = Me) can be obtained in optically active form by condensation of diene 1 with methyl glyoxylate in the presence of dichlorotitanium (R)-binaphthol catalyst (3) [45]. 

Dihydro-2fT-pyran (14) fragments by the RDA pathway with charge retention on the diene fragment (14a). Hydrogen radical abstraction from the [M]t ion produces (14b),... 

Dihydro-2//-pyran-2-ones, via ring-closing diene... 

J. Jurczak, T. Bauer, and S. Jarosz, Stereospecific synthesis of 5,6-dihydro-2//-pyran system. High-pressure cycloaddition of l,2 3,4-di-0-isopropylidene a-D-galactopyranose-6-ulose to 1-methoxybuta-l,3-diene, Tetrahedron Lett., 25 (1984) 4809—4812. 

Phosphonoacrolein, (Et0)2P(0)C(CH0)=CH2, takes part in hDA reactions with alkenes and cyclic conjugated dienes, to give phosphono-substituted 3,4-dihydro-2W-pyrans and their annulated derivatives. The reaction with alkynes gives the 1 1 adduct, a 4//-pyran, initially but this undergoes a second cycloaddition leading to a tetrahydropyrano[3,2-6]pyran 3... 

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>. 

Sequential one-pot RCM-cyclisation of dienes and alkene isomerisation have been achieved through conversion of the Ru-alkylidene RCM catalyst into a Ru-hydride catalyst, providing an efficient route to 3,4-dihydro-27/-pyrans from acyclic dienes <02JA13390>. 

The 4-vinyloxetan-2-ones generated in a Pd-catalysed [2+2] cycloaddition between ketene and a,P-unsaturated carbonyl compounds undergo a spontaneous allylic rearrangment. A zwitterionic intermediate is proposed that cyclises to a 3,6-dihydro-2//-pyran-2-one, but which may alternatively decarboxylate to a diene <02T5215>. 

Tandem RCM and cross-metathesis reactions of allyl hexa-l,5-dien-3-yl ether with alkenes leads to 2-alkylidene 3,6-dihydro-27f-pyrans (Scheme 6) <07TL1417>. 

The aza-Diels-Alder reaction of substituted lf/-indole-2-carbaldehydes 1323 with Danishevsky s diene 1324 proceeds with a high degree of diastereoselectivity providing highly functionalized l-R -2-(Tmethyl-lf/-indol-2-yl)-2,3-dihydro-4(l//)-pyridinones 1325 which were further elaborated into novel polycyclic heterocycles (Equation 289) <2002TL29>. Attempts to form the imine of 12/-indole-2-carbaldehyde 1326 in situ in the presence of diene 1324 and zinc chloride or zinc triflate at 0 °C or at room temperature did not afford the expected cycloadduct 1327. Instead, 2-(177-indol-2-yl)-2,3-dihydro-477-pyran-4-one 1328 and the 5-hydroxy-l-methoxy-5-(l/7-indol-2-yl)-Tpenten-3-one 1329 were isolated in 45% and 25% yields, respectively (Equation 290). 

Mannich ketobases may also be useful materials for the synthesis of O-hetcrocycles (Fig. 134), as they behave as masked heterodienes in the reaction with dicnophiles. The a,P-unsaturatcd ketone formed by elimination of the amino group can in fact undergo cycloaddition by the dienophile to give the dihydro-4H-pyrans 346. In the event that an HX molecule is eliminated, the pyran ring is formed. - - - The above reaction is also quite favored by dienes, and it can be competitive with the diene synthesis shown in Fig. 129. 

H-Pyran 6-(l,2-Diacetoxy-ethyl)-2-methoxy-5,6-dihydro- E14a/1, 434 (1,3-Dien-l-ol-ether + R-CHO)... 

H-Pyran 6-(l-tert.-Butyloxycarbo-nyl-amino-ethyl)-4-methoxy-2-oxo-5,6-dihydro- E21c, 2933 [RHN-CHR-CHO + 1,3-(OR)2 — 1 -OSiR3 — 1,3-dien]... 

Cationic palladium(II) complexes, [PdL2(PhCN)2](BF4)2 (L2 = DPPP, DPPF), catalyze the reaction of non-activated dienes with aldehydes, affording the corresponding 5,6-dihydro-2//-pyrans (Sch. 55) [200],... 

The [4 + 2] cycloaddition of a,p-unsaturated aldehydes and ketones (1-oxa-1,3-dienes) to enol ethers (Diels-Alder addition with inverse electron demand) has been an attractive route for the synthesis of 3,4-dihydro-2 -pyrans [143-146], which can be converted into deoxy- and dideoxypyranosides [147,148]. 

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