Bicyclic a-pyrans

Bicyclic a-pyrans and -pyrones. The Ni(0)-catalyzed reaction of an aldehyde with a terminally dialkyl-substituted 1,7-octadiyne results in bicyclic a-pyrans. This reaction is highly dependent on the length of the chain connecting the triple bonds and on the presence of the terminal substituents. 

A novel cycloaddition of diynes with aldehydes is catalyzed by the same metal system, giving rise to bicyclic a-pyrans after 1,5-hydrogen shifts. Yields of these sensitive compounds are remaritably high (equation 52). ... 

A 6-endo cyclization by a y-epoxy alcohol can be accomplished through the presence of an appropriately disposed electron-withdrawing group, as found in the total synthesis of (+)-phonomactin. Treatment of the hydroxy-epoxy ketone 30 (R = H) with HC1 afforded the bicyclic compound 31, containing a pyran-4-one ring, in which nucleophilic attack of the y-OH group occurred at the oxirane carbon distal from the unfavorable electronic effect of the carbonyl group (Scheme 8.7) [20a]. 

If two cyclic 1,3-dioxo fragments are connected via a monocarbon 2,2 -bridge, only one undergoes cyclodehydration. Thus bicyclic 4//-pyran systems 20b (R = H or Ph) were obtained after the reaction of triketone 53... 

Enynals 104 can undergo a palladium-catalyzed cyclization to form the pyrylium intermediate 105, which upon deprotonation affords the triene 106. In the presence of DM AD, a [2+2]-cycloaddition then occurs to form the tricyclic 4//-pyran intermediate 107, which undergoes expansion of the cyclobutene ring to afford the bicyclic 4//-pyrans 108 (Scheme 34) <2004S1409>. 

Nonclassical cannabinoids consist of bicyclic and tricyclic analogues of A -THC that lack a pyran ring examples include CP55940, CP47497, CP55244 and HU-308 (Fig. 6). They are, therefore, closely related to the classical cannabinoids. 

Elinson et al. used a catalytic amount of sodium acetate for the synthesis of bicyclic 4//-pyran derivatives of... 

The bicyclic system 5 can also be used to prepare annulated systems by cycloaddition-cycloreversion processes. With 2//-pyran-2-one (6) a mixture of cycloadducts is formed on... 

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. 

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. ... 

The term non-classical cannabinoids is applied to a group of bicyclic compounds identified by researchers at Pfizer in the 1980s [129], These compounds lack the pyran ring of the classical cannabinoids and the second phenolic hydroxyl group of the cannabidiols, resulting in a simplified substructure represented by CP 47,497 (192) [130, 131], The non-classical cannabinoids still retain the three main pharmacophoric elements described above for the classical cannabinoids and the SAR in these regions parallels that of the classical cannabinoids [132]. 

The benzopyran ring is not essential for activity. The pyran oxygen can be substituted by nitrogen or can be eliminated in open-ring mono- or bisphenolic compounds. The recently developed CB2-selective ligand HU-308 (5) is an example of such a bicyclic cannabinoid (Hanus et al., 1999). 

Both natural and non-natural compounds with a 2ff,5ff-pyrano[4,3-fc]pyran-5-one skeleton are of interest in medicinal chemistry. Several natural products, such as the pyripyropenes, incorporate this bicyclic ring system. The group of Beifuss has described an efficient microwave-promoted domino synthesis of the 2ff,5H-pyr-ano[4,3-fo]pyran-5-one skeleton by condensation of a,/3-unsaturated aldehydes with 4-hydroxy-6-methyl-2]-f-pyran-2-one (Scheme 6.244) [428]. It is assumed that in the presence of an amino acid catalyst a Knoevenagel condensation occurs first, which is then followed by a 6jr-electron electrocyclization to the pyran ring. While the conventional thermal protocol required a reaction time of up to 25 h (refluxing ethyl... 

Pyran-4-ones bear an obvious structural similarity to the all-carbon cyclohexadienones discussed above. However, the original studies of their photochemical behavior revealed only dimerization processes to produce a cage product resulting from two successive head-to-tail [2 + 2]-photocycloadditions (Scheme 29)54. Much later, small amounts of substituted furfural 121 were observed during the irradiation of 11955a. It was speculated that 121 could arise from bicyclic epoxide 120, an intermediate analogous to those formed in cyclohexadienone photochemistry. Subsequent reports noted that further irradiation of... 

A bicyclic -y-pyranone was isolated in —1% yield from an acidified, refluxed solution of D-erythrose (6). It was proposed that the compound, 4a,5,6,7a-tetrahydrocyclopenta[ >]pyran-4,7-dione (10), is formed (by way of 9) from two molecules of D-erythrose, namely, an enediol (8) and a dehydrated form (7). Feather and Harris pointed out that D-erythrose would lose two molecules of water to form an intermediate (7) prior to coupling with the enediol 8 (see Scheme 2) to give 9. 

Alkyl bromides have been shown to add to 5-trifluoroacetyl-3,4-dihydro-2/7-pyrans in the presence of zinc powder (Scheme 31). When BrCH2C02Me is employed as the alkyl bromide, after the initial addition, the ester may easily be cleaved under acidic conditions and the product undergoes spontaneous cyclization to afford a bicyclic lactone <1999JEC141>. 

A substituted dihydropyran, 3,4-dihydro-2-(hydroxymethyl)-2ff-pyran (176), was employed by R. K. Brown and coworkers76 77 as the substrate in a total synthesis of hexoses (see Section III,2). The first steps in this method consisted in (1) intramolecular addition of the hydroxyl group to the double bond, to afford the bicyclic compound 177, and (2) bromination of 177 to the monobromo derivative 178. 

The effect of solvent and sensitizer on the course of photolysis of pyran-2-one is evident from Scheme 11. When methanol is present, either the ring is cleaved and an ester (237) is formed, or, with a sensitizer, dimers (238) are produced in equal amounts. The bicyclic lactone (227) and the ester (237) are believed to be formed via singlet excited states of the pyranone while the dimers (which are photostable) result from the triplet state (68TL5279). 

An efficient method for pentannulation using acyloxy-functionalized pyrans that evolve from readily available propargylic esters has been developed. Utilizing a range of epoxides, pentannulation is achieved using PtCl2 to obtain bicycles containing a... 

Examples of fused pyrans which can be obtained in a similar manner include 6-oxasteroids (95JCS(P1)1089) and bicyclic vinyl ethers (95CC1117), whilst a double radical cyclisation of 3-alkoxyacrylates features in a synthesis of 3Z-dactomelyne (95JA8017). 

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