Pyrans, dihydro cycloaddition reactions synthesis

Inverse electron-demand Diels-Alder reaction of (E)-2-oxo-l-phenylsulfo-nyl-3-alkenes 81 with enolethers, catalyzed by a chiral titanium-based catalyst, afforded substituted dihydro pyranes (Equation 3.27) in excellent yields and with moderate to high levels of enantioselection [81]. The enantioselectivity is dependent on the bulkiness of the Ri group of the dienophile, and the best result was obtained when Ri was an isopropyl group. Better reaction yields and enantioselectivity [82, 83] were attained in the synthesis of substituted chiral pyranes by cycloaddition of heterodienes 82 with cyclic and acyclic enolethers, catalyzed by C2-symmetric chiral Cu(II) complexes 83 (Scheme 3.16). 

A peroxy acid mediated oxidative rearrangement of 2-alkoxy-3,4-dihydro-2//- pyrans affords 5-alkoxytetrahydrofuran-2-carbaldehydes (79JCS(Pi)847>. This reaction pathway was used in developing a method for the synthesis of optically active monoalkylfurans. (S)-2-Ethoxy-5-s-butyl-3,4-dihydro-2//-pyran (319), obtained through a cycloaddition reaction of (S)-2-s-butylacrolein to ethyl vinyl ether, was converted to (S)-2-s-butyl-5-ethoxytetrahydrofuran-2-carbaldehyde (320) (Scheme 85). 

The use of pyran intermediates for the synthesis of these ring systems has presented few examples. The [4 + 2] cycloaddition of 5-ethenyl-3,4-dihydro-2//-pyrans with DEAD yields compounds (500) <86CB3204>. Reaction of the esters (501) with hydrazine hydrate gave the pyranodiazines (502) <86MI 716-01). 

Annulation of heterocycles with a cyclobutene ring has been achieved by photochemical (2 + 2)-cycloaddition with acetylenes. Both maleic anhydride and N-substituted maleimides yielded 3-oxa- or 3-aza-bicyclo[3.2.0l-hept-6-ene-2,4-diones (167).,89,9° Vinylene carbonates also entered into a cycloaddition reaction with acetylenes to afford 168, which has been employed as starting material for the synthesis of cyclo-butadiene(tricarbonyl)iron or cyclobutenedione.19,-193 3,4-Dihydro-2/f-pyran and 5-methyl-2,3-dihydrofuran reacted with diphenylacetylene to... 

ExceUent yields, diastereo- and enantioselectivities are achieved in the synthesis of 3,4-dihydro-2J/-pyran-2-ones through asymmetric cycloaddition reactions of disubstituted ketenes with p,y-unsaturated a-keto esters carried out in the presence of a chiral Lewis acid (Scheme 44) (140L134). 

The preparation of 5-ACETYL-l,2,3,4,5-PENTAMETHYLCYCLO-PENTADIENE is of value in the synthesis of pentamethyleyclo-pentadiene and many pentamethylcyclopentadienyl metal carbonyl derivatives that are more soluble in organic solvents than those derived from cyclopentadiene. Simple preparations of 5,6-DIHYDRO-2-PYRAN-2-0NE and 2-//-PYRAN-2-ONE make these hitherto rather inaccessible intermediates available for cycloaddition and other reactions. The already broad scope of the Michael reaction has been widened further by including an efficient preparation of ETHYL (E)-3-NITROACRYLATE. Workers in the field of heterocyclic chemistry will find a simplified method for the preparation of 2,3,4,5-TETRA-HYDROPYRIDINE of help. 

More functionalized 5,6-dihydro-2H-pyran-derivatives 71 and 72 have been prepared [26] by cycloaddition of 1 -methoxy-3-trialkylsilyloxy-1,3-butadienes 69 with t-butylglyoxylate (70) (Scheme 5.6). Whereas thermal reactions did not occur in good yields because of the decomposition of the cycloadducts, application of pressure (10 kbar) allowed milder conditions to be used, which markedly improved the reaction yields. The use of high pressure also gives preferentially en Jo-adduct allowing a stereocontrolled synthesis of a variety of substituted 5,6-dihydro-2H-pyran-derivatives, which are difficult to prepare by other procedures. 

Dihydro-2H-pyran-2-ones (e. g., 4-195) are valuable intermediates in the synthesis of several natural products [67]. Hattori, Miyano and coworkers [68] have recently shown that these compounds can be easily obtained in high yield by a Pd2+-catalyzed [2+2] cycloaddition of ct, 3-unsaturated aldehydes 4-192 with ketene 4-193, followed by an allylic rearrangement of the intermediate 4-194 (Scheme 4.42). In this reaction the Pd2+-compound acts as a mild Lewis acid. a,(3-unsaturated ketones can also be used, but the yields are below 20%. 

Cycloadditions involving the more nucleophilic vinyl ethers are easier than those above and the reaction has considerable synthetic potential. The reactants are heated at 180-190 °C in a sealed vessel and the adduct is rapidly formed in high yield (50JA3079, 51JA5267). Full experimental details have been published for the synthesis of 3,4-dihydro-2-methoxy-4-methyl-2/f-pyran from methyl vinyl ether, and the same technique was used to prepare a further 13 dihydropyrans (630SC(4)3il>. 

It has since been shown that the cycloaddition is catalyzed by transition metal salts (78JOC667). Although the yields are generally lower than irr the uncatalyzed reaction, this is outweighed by the advantages of shorter reaction times and a lower cyclization temperature. Illustrative examples of the formation of 2-alkoxy-3,4-dihydro-2//-pyrans are presented in Table 3, which includes a comparison of the two methods of synthesis. 

The reaction between vinyl ethers and unsaturated carbonyl compounds, which provides a powerful synthetic route to dihydropyrans, has been adapted to the synthesis of pyran-2-ones (72CC863). 2-Chloro-1,1 -dimethoxyethylene, which is a protected form of chloroketene, undergoes cycloaddition with a number of enones to give the cis or trans isomers of 3-chloro-3,4-dihydro-2,2-dimethoxypyrans (338) and (339) or a mixture of both. Although... 

The [4 + 2 ]cycloaddition of the carbonyl group of aldehydes as well as of ketones and 1,3-butadienes is a well established method for the synthesis of 5,6-dihydropyrans which are useful substrates for the preparation of carbohydrates and many other natural products. Several excellent reviews on this topic have appeared [10-12,14,22]. The first example of this type of reaction using 2,4-dimethyl-1,3-butadiene and formaldehyde to give the 2,4-dimethyl-5,6-dihydro-2/f-pyran in 60% yield was published by Gresham and Steadmen in 1949 (Scheme 2-1, Eq. 1) [57]. 

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. 

This is illustrated in Scheme 12 by the example of the synthesis of p-lactam 28.Until now 14 structures derived from dihydro-2H-pyrans and glycals were obtained, and are shown in Scheme 13. The same procedure could be applied to the cycloaddition of trichloroacetyl isocyanate to the furanoid glycal 29.The reaction proceeded with the same high stereoselectivity to produce [2+2] and [4+2]cycloadducts having the a-D-gluco configuration (Scheme 14). J Deprotection led to the formation of stable compound 30. 

---