Pyran Formation

Replacing the ester by a ketone sufficiently enhances the reactivity of the Michael acceptor that the Michael addition occurs during the alkene-alkyne coupling to give the tetrahydropyran directly, as shown in Equation 1.45. This facile atom economic tandem process has already proven effective in streamlining syntheses to complex targets [42, 43]. 

Replacing the (3,y-unsaturated carbonyl group by an alkoxy group offers a different cyclization process for tetrahydropyran formation, namely simple acetalizations as shown in Equation 1.46 [44], 

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Fused tetrahydro-2//-pyrans can also be obtained in high stereoseleclivity by oxythallation. In fact, starting from /ra .v-2-[( )-2-methyl-2-butenyl]cvclohexanol (7), tetrahydro-2//-pyran formation proceeds via initial cyclization to the tetrahydrofuran, followed by ring expansion, giving the /ra/z.v-6,6-fused product 8 in 50% isolated yield13. 

Application of the Stobbe reaction to 2-benzoyldibenzofuran gives access to two substituted 1-naphthols 49 and 50 which after cyclisation and possible further manipulation are substrates for pyran formation -with l,l-diphenylprop-2-yn-l-ol (Scheme 17). The resulting heptacyclic photochromes absorb in the range 570 - 600 nm with half-lives of 20 -70 s <98WOP32037>. 

Synthesis of pyranopterin-dithiolene complex exhibiting reversible pyran formation... 

Richter M, Busch B, Ishida K, Moore BS, Hertweck C (2012) Pyran formation by an atypical CYP-mediated four-electron oxygenation-cyclization cascade in an engineered aureothin pathway. Chembiochem 13 2196-2199... 

Base-mediated 4//-pyran formation with nitrile-groups bearing CH-acids... 

The potential-energy surface for the rearrangement of cis- and tra i-4,5-epoxyhexan-l-ol with acid or the Lewis acid BF3 to five- and six-membered cyclic ethers has been examined by ab initio methods. The preference for furan rather than pyran formation is attributed to the more favourable O—C—O bond angles in the transition structures for furan formation. 

HYDROGENATED PYRANS FORMATION FROM FORMALDEHYDE DIMERS... 

FIGURE 10.6 The scheme of hydrogenated pyrans formation from alkenes and FD. Proton transfer at the stage b d is suggested to a corresponding mechanism [25]. 

TABLE 10.3 Energy Parameters of the Hydrogenated Pyrans Formation Reactions, kJ/ mol... 

The role of formaldehyde dimer in 0-containing heterocycles formation by the Prins reaction have been investigated. It was shown that the 1,3-di-oxanes, hydrogenated pyrans and oxetanes can be can be obtained from formaldehyde dimers and alkenes in the gas phase. The activation energy of these reactions is different. It is lower for 1,3-dioxanes formation, and higher for oxetanes formation. Thus formation of 1,3-dioxanes happens in the conditions of kinetic control. Opposite, the hydrogenated pyrans formation happens in the conditions of thermodynamic control... 

FIGURE 11.3 The scheme of hydrogenated pyrans formation from alkenes and FD. 

Unpredictably due to the results of our calculations, the formation of ox-etanes can also be accomplished with formaldehyde olygomers participation and 1,3-dioxanes and hydrogenated pyrans formation (Fig. 11.6). 

The thiepin system 31 is formed quantitatively by ring expansion of the diazoacetate derivative 30 via carbene formation catalyzed by 7r-allylpalladium chloride and its intramolecular insertion[31], The 4-diazomethyl-4//-pyrane 32 is expanded to the oxepine 33 in quantitative yield with the same catalyst[32]. 

There are several examples of the formation of pyridazines from other heterocycles, such as azirines, furans, pyrroles, isoxazoles, pyrazoles or pyrans and by ring contraction of 1,2-diazepines. Their formation is mentioned in Section 2.12.6.3.2. 

Finally, a novel synthetic route involves formation of the pyridine ring from a fused pyran intermediate, e.g. (139) - (140) (70CB1250, 80JOC1918, 73JCS(P1)823). If a pyrylium salt is used, a quaternary pyridopyrimidinium salt such as (141) is formed 77KGS14S4). 

Kojic acid — see also Pyran-4-one, 5-hydroxy-2-hydroxymethyl-, 3, 611 acylation, 3, 697 application, 3, 880 occurrence, 3, 692 reactions, 3, 714, 715 with amines, 3, 700 with phenylhydrazine, 3, 700 synthesis, 3, 810 Kokusagine occurrence, 4, 989 Kokusaginine occurrence, 4, 989 synthesis, 4, 990 Koopmans theorem, 2, 135 Kostanecki-Robinson reaction chromone and coumarin formation in, 3, 819-821 mechanism, 3, 820 flavones, 3, 819... 

These reactions are related to the formation of pyrroles and quinolines from aminocarbonyl compounds and acetylenes (582,583) and may be contrasted with the formation of pyran derivatives by electrophilic attack on an enamine, followed by addition of an oxygen function to the imonium carbon (584-590). 

Despite the increasing information on the photochemistry of 2,4-dienones and other unsaturated ketones, as well as on the ring-chain valence isomerism of halogen-substituted pyran and dihydi opyran systems,the data are still very scarce. The intermediate formation of pyrans valence-isomeric with unsaturated carbonyl compounds in the pyridine syntheses based on reactions of ammonia with aldehydes or ketones, advocated by various authors (cf. Section II,B,2,f), is still rather speculative. (See also Section II,B,2,e for the valence isomerism of 5-chloro-2,4-dienones with pyrylium chlorides.)... 

By contrast, heating benzo-2//-pyran 6 with acetic acid leads to the formation of the 4H isomer 7 (Scheme 2) [77ACS(B)496]. 

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. 

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