Dihydropyran derivative

Tamura etal.2 described only briefly in their paper on dihydropyran derivatives that 6,8-dioxabicyclo[3.2.1]octan-7-one 53 and its methyl derivative underwent polymerization in the presence of a large amount of boron trifluoride etherate to give polymers with molecular weights of several hundreds. 

Acyclic dienes react with glyoxylic acid via an oxo-Diels-Alder reaction to give dihydropyran derivatives (Eq. 12.53). An excellent application of the oxo-Diels-Alder reaction is reported by Lubineau et al. in the synthesis of the sialic acids, 3-deoxy-Z)-manno-2-octulosonic acid (KDO) and 3-deoxy-D-glycero-D-galacto-2-nonulosonic acid (KDN).123... 

Scheme 5.16 4-Pentynol cyclization leading to dihydropyran derivatives Stepwise.

Substitution of a methoxycarbonyl group for the hydroxymethyl group brings about an interesting, but not unexpected, change in the reaction. In aqueous acetic acid, 63 forms the dihydropyran derivative... 

Under comparable conditions the submitters found that the corresponding dihydropyran derivatives were similarly obtained by the condensation of acrolein with methyl vinyl ether in 80-81% yield, with ethyl vinyl ether (77-85% yield), with w-butyl vinyl ether (82% yield), with ethyl isopropenyl ether (50% yield), and with w-butyl cyclohexenyl ether (40% yield). Other <, /3-un-saturated carbonyl compounds that have thus been condensed with ethyl vinyl ether are crotonaldehyde (87% yield), meth-acrolein (40% yield), a-ethyh/3-n-propylacrolein (54% yield), cinnamaldehyde (60% yield), /3-furylacrolein (85% yield), methyl vinyl ketone (50% yield), benzalacetone (75% yield), and benzal-acetophenone (74% yield). 

Besides acyclic unsaturated carbonyl compounds, their alicyclic analogues may be used, leading to fused dihydropyran derivatives. Cyclic vinyl ethers have also been utilized in the process. 

Where there is an electron-rich olefinic double bond in the diazoketone as in the 2-substituted 3,4-dihydropyran derivative 47, the intramolecular cyclopropanation produces oxatricyclic ketones, e.g. 48 (equation 57)86 87. Rhodium(II) acetate is the catalyst of choice for this transformation. An interesting application of this method is found in a stereoselective synthesis of ( )-/ -chamigrene 49 (equation 5S)88. 

Azido-phenylselenenylations of olefinic compounds can be effected with BAIB/PhSeSePh/NaN3 in CH2C12 (Scheme 14) [37]. Such additions proceed in anti-Markovnikov fashion and appear to be initiated by addition of the azido radical to the C,C-double bond. While cyclohexene and ds-4-octene gave 3 1 and 2 1 mixtures of diastereomeric adducts under these conditions, dihydropy-ran was converted cleanly to the trans-addition product. Regioselective azido-phenylselenenylations of dihydropyran derivatives and O-protected glycals with this reagent have also been documented [21,38,39]. 

M.-R. Brescia, Y. C. Shimshock, and P. DeShong, Regioselectivity in the palladium-catalyzed addition of carbon nucleophiles to dihydropyran derivatives, J. Org. Chem., 62 (1997) 1257-1263. 

A novel formal inverse-electron-demand hetero-Diels-Alder reaction between 2-aryl-a,/3-unsaturated aldehydes and ketones produces dihydropyran derivatives stereo-specifically.161 The inverse-electron-demand Diels-Alder reaction of 3,4-r-butylthio-phene 1-oxide with electron-rich dienophiles shows vyn-jr-face and endo selectivity.162 (g) The inverse-electron-demand Diels-Alder reaction of dimethyl l,2,4,5-tetrazine-3,6-dicarboxylate with a variety of dienophiles produces phthalazine-type dihydrodiol and diol epoxides which were synthesized as possible carcinogens.163... 

Vinyl triflate 212 and ethyl 2-acetylpent-4-enoate react under palladium(n) catalysis to afford the steroidal 3,4-dihydropyran derivative 213. The reaction proceeds via an intramolecular cyclization of the a-allylpalladium intermediate 214 (Scheme 63) <1998SL888>. 

In early work which have been summarized very recently [23], Danishefsky et al. have investigated hetero Diels-Alder reactions of carbonyl compounds in order to yield glycals. Numerous further contributions to the stereoselective synthesis of dihydropyran derivatives by high pressure or Lewis acid induced Diels-Alder reactions of carbonyl compounds have been made by Jurczak et al.,... 

Dihydropyran derivatives (339) have also been obtained by the hetero Diels-Alder reaction between electron-rich olefins such as enol ethers 338 and amino ketones 337 bearing electron-withdrawing groups such as methoxycarbonyl, trifluoromethyl or... 

To illustrate the practical use of the three programs [143], a dihydropyran derivative, ethyl-2-methyl-5,6-dihydro-o -pyran-6,6-dicarboxylate has been chosen as an example. This unsaturated, sugar-related compound in solution exists in an equilibrium of two conformations. 

Strong reasons would support this wrong assumption. On one hand, besides the only C=C bond of II, there appears to be nothing in this molecule reactive enough towards the diene, save perhaps for the a-keto ester function. However, most people believe that the only way to drive a carbonyl to react in a Diels-Alder fashion is by placing it in the diene portion such as in the synthesis of dihydropyran derivatives (see Scheme 33.2). 

Aryl-substituted contiguous cyclopropyloxiranes are converted to dihydropyran derivatives (Eq. 393). ... 

A total synthesis of adaline (550) has been performed (73BSB699). The vinyl ketone 547 was submitted to hetero Diels-Alder reaction with methyl vinyl ether to yield the dihydropyran derivative 548 in 60% yield. Acid hydrolysis of 548 produced the keto aldehyde 549. Finally, a Mannich reaction involving... 

The addition of isocyanates to glycals, which has been studied thoroughly in connection with new methods of synthesizing lactams [256], usually affords a mixture of [2+2] and [4+2] cycloadducts. These primary reaction products are rather unstable and slowly rearrange to unsaturated amides, which can often be isolated directly from reaction mixtures [257,258]. In the case of simple dihydropyran derivatives 168, unsaturated A-substituted C-2 formamides 170 are the only isolable products (O Scheme 57) [259,260]. 

There is evidence strongly supporting the two-step mechanism. For example, the zwitterionic intermediate has been trapped, and, furthermore, cis- and tranj -isomeric electrophilic olefins give the same product The reaction has been applied to many different conjugated systems and its regio- and stereoselectivity has been extensively studied . Some examples of this heterocycloaddition include the preparation of 1,4-dihydropyran derivative 331, 332 and 333 by intermolecular reaction. In another example 336 was obtained by intramolecular enamine-enal cycloaddition from... 

One classical polyol dehydration reaction is the transformation of glycerol to acrolein in the presence of fused, powdered KHSO4 [94]. Another important example is the dehydration of substituted 1,2,5-triols (8) to dihydropyran derivatives... 

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