Dienes 2-pyrones

The 2-pyrones can behave as dienes or dienophiles depending on the nature of their reaction partners. 3-Carbomethoxy-2-pyrone (84) underwent inverse Diels-Alder reaction with several vinylethers under lanthanide shift reagent-catalysis [84] (Equation 3.28). The use of strong traditional Lewis acids was precluded because of the sensitivity of the cycloadducts toward decarboxylation. It is noteworthy that whereas Yb(OTf)j does not catalyze the cycloaddition of 84 with enolethers, the addition of (R)-BINOL generates a new active ytterbium catalyst which promotes the reactions with a moderate to good level of enantio selection [85]. 

A marked dependence of the reaction yield on the nature of the Lewis-acid catalyst and on the diene-dienophile ratio was observed (Table 5.4). 2-Pyrone (165) reacted at 18.5 kbar with methylacrylate but the reaction was unregiose-lective and undiastereoselective. 

Pyrones are useful dienes, although they are not particularly reactive. The adducts have the potential for elimination of carbon dioxide, resulting in the formation of an aromatic ring. Pyrones react best with electron-rich dienophiles. Vinyl ethers are frequently used as dienophiles with pyrones. The regiochemical preference places the dienophile donor ortho to the pyrone carbonyl. 

BINOL in conjunction with TiCl2(0-/-Pr)2 gives good enantioselectivity in a D-A reaction with a pyrone as the diene.116 This is a case of an inverse electron demand reaction and the catalysts would be complexed to the diene. 

When benzyne is generated in the absence of another reactive molecule it dimerizes to biphenylene.132 In the presence of dienes, benzyne is a very reactive dienophile and [4+2] cycloaddition products are formed. The adducts with furans can be converted to polycyclic aromatic compounds by elimination of water. Similarly, cyclopentadienones can give a new aromatic ring by loss of carbon monoxide. Pyrones give adducts that can aromatize by loss of C02, as illustrated by Entry 7 in Scheme 11.9. 

The Baccatin III synthesis by K. C. Nicolaou and co-workers is summarized in Scheme 13.54. Diels-Alder reactions are prominent in forming the early intermediates. In Step A the pyrone ring served as the diene. This reaction was facilitated by phenyl-boronic acid, which brings the diene and dienophile together as a boronate, permitting an intramolecular reaction. 

Cyclic dienes also react readily with ADC compounds although in many cases the initial adducts are not isolable. 1-Substituted pyrid-2-ones give Diels-Alder adducts with ADC compounds, although 2-pyridone itself gives only the substitution product (e.g., 113).174 2-Pyrone gives a 1 2 adduct with PTAD, since the initial adduct (114) rapidly loses C02 to generate a diene which then reacts with more PTAD.175 The initial adducts of ADC compounds with cyclopentadienones,176 and 3,4-dimethyl-1-phenylphos-phole 1-sulfide (115)177 also regenerate a diene by loss of CO and PhP=S, respectively. 

Scheme 6.108 Products ofthe interception of 1,2,4,6-cyclohepta-tetraene (5) with 1,3-diphenylisobenzofuran, anthracenes, 2,5-dimethyl-3,4-diphenylcyclopenta-2,4-dien-l-one, methyl 2-pyrone-5-carboxylate, tropones, 8,8-dicyanoheptafulvene and 1,3,5-cycloheptatrienes.

These phenomena can be illustrated by the cycloaddition reactions of fulvenes with electron-deficient a-pyrones. In general, the Diels-Alder reactions of electron-deficient dienes such as 458 with 6-alkyl substituted fulvenes favor addition across one of the endocyclic... 

The first report of a cycloaddition reaction in the presence of an optically active catalyst13 appeared in 198314a. The dienes 14 add to benzaldehyde in the presence of 1 mol% of the chiral lanthanide NMR shift reagent Eu (hfc)3, i.e. tris[3-(heptafluoropropyl-hydroxymethylene)-(+)-camphorato]-europium(III), to give, after treatment with trifluo-roacetic acid, the dihydro-y-pyrone 15 enriched in the (R)-enantiomer, the degree of... 

It has been shown22 that the reaction of the diene 4 with aldehydes RCHO in the presence of a catalyst prepared from (R)-BHMOL (33) and Ti(OPr-i)3, which affords the dihydro-y-pyrones 35 in good yields and high ee, proceeds by a two-step sequence via the open-chain adducts 34, which cyclize to the products on treatment with trifluoroacetic acid (equation 20). 

The Deng group identified QN-derived thiourea 121 and QD -derived thiourea 124 to be also efficient promoters of enantio- and diastereoselective Diels-Alder reactions between the 2-pyrone diene 3-hydroxypyran-2-one and the dienophiles fumaronitrile, maleonitrile as well as acrylonitrile, while various C9-hydroxy acylated and alkylated (dihydro)cupreines and (dihydro)cupreidines failed for the same reactions under identical conditions (e.g., 97% yield, 15% ee, 64 36 endoxxo) [289], Catalysts 121 and 124 (5mol% loading), however, produced the corresponding Diels-Alder adducts 1-3 with synthetically useful enantioselectivities (85-... 

It has been found that l,3-di(ethoxycarbonyl)allene reacts readily with such heterocyclic dienes as furan, pyrrole, and pyrone derivatives. The furan adduct 383, obtained in 87% yield, was hydroxylated, and after acetonation, was cleaved251 with ozone, to afford intermediate 384. An approach to the conversion of 384 into C-glycosyl compounds by hydride-promoted scission of the C-5-C-6 bond was disclosed.255... 

Such cycloadditions are dependent on the interactions of the azepine HOMO and the diene LUMO. Theoretical consideration of these orbitals reveals that bonding overlap is favourable for C-6—C-7 and C-4—C-5 additions and that, on the basis of secondary orbital interactions, the endo product is favored. Experimentally, however, it is found that additions are periselective and C-4—C-5 addition predominates in the cycloaddition of 1//-azepines with cyclopentadienones, isobenzofurans, tetra- and hexa-chlorocyclopentadienes, 1,2,4,5-tetrazines, a-pyrones and 3,4-diazacyclopentadienones (8lH(15)1569). 

Attempts to effect cycloadditions with a-pyrone as the diene system failed (78JOC315). However, the more electron-deficient a-pyrone-5- (or 6-) carboxylates add slowly (5 days in boiling toluene) to the l//-azepine to furnish a mixture of the [2+4]7t (25%) and the [6 + 4]7r (20%) adducts (153) and (154) respectively. On prolonged heating (7 days) in toluene solution adduct (153) extrudes CO2 to form the benzazepine (155 R1 = CC Me R2 = Et) <78H(11)401). 

Related attempts at intercepting the trans double bond of the stable mono-trans ben-zazonine (6) with use of dienes (101) and (102) led instead to cycloaddition onto the isolated cis double bond with the formation of cycloadducts (105) (75CC149) and (106) (77TL4465) respectively. Further, attempted thermal extrusion of CO2 from (106) activated deepseated rearrangement to (107), the operational details of which were investigated with the use of deuterium-labeled a-pyrone (102). 

Aldehyde 63 (950 mg, 2 mmol) and anhydrous ZnBr2 (450 mg, 2 mmol) in dry THF (10 mL) were stirred at room temperature for 1 h. To the homogeneous solution was added diene 62 (1.3 g, 4 mmol), and the reaction mixture was stined at room temperature for 48 h. TFA (1 mL) was then added, and after an additional 5-min stirring, the solution was partitioned between EtjO (30 mL) and a saturated NaHCOj solution (30 mL). The organic layer was dried (MgS04), and concentrated in vacuo. Flash chromatography (hexanes-EtOAc, 6 4) of the residue afforded an unseparable mixture (2 1) of pyrones 64a and 64b (800 mg, 60%) as an oil. 

This method affords a-pyrone in quantity and in good yield not achieved previously.3 The compound has considerable possibilities in Diels-Alder reactions, such as a decarboxylative double diene synthesis.5... 

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