Dihydropyran, reduction

Reaction of 25 with dihydropyran serves to protect the hydroxyls by converting these to the tetrahydropyranyl ethers (THP). Reduction of the lactone thus protected with diisobutyl... 

Reductive amination of dihydropyran (which may be regarded as the dehydration product of the cyclic acetal of 5-hydroxy-pentanal) in the presence of isopropylamine and a trace of acid affords the aminoalcohol, 96. Treatment of this compound with thionyl chloride affords the haloamine, 97. Alkylation of the quinoline, 92, with this halide yields pentaquine (98). ... 

Dihydro-2f/-pyran-2-one has been prepared by reductive cycliza-tion of 5-hydroxy-2-pentynoic acid [2-Pentynoic acid, 5-hydroxy-], which is obtained in two steps from acetylene [Ethyne] and ethylene oxide [Oxirane] 3 and by the reaction of dihydropyran [277-Pyran, 3,4-dihydro-] with singlet oxygen [Oxygen, singlet].4,5 2ff-Pyran-2-one has been prepared by pyrolysis of heavy metal salts of coumalic acid [2//-Pyran-5-carboxylic acid, 2-oxo-],8 by pyrolysis of a-pyrone-6-carboxylic acid [211 - Pyran-6-carboxyl ic acid, 2-oxo-] over copper,7 and by pyrolysis of coumalic acid over copper (66-70% yield).8... 

Reduction, by hydrogen and Raney nickel—Continued dihydropyrane to tetrahydropy-ranc, 23, 90... 

All reactions listed in Tables 5-7 were carried out under a nitrogen atmosphere, but with the rhodium or palladium catalysts no noticeable or only minor reduction in cyclopropane yields was observed when air was present. In contrast, air clearly had a yield-diminishing effect in the CuCl P(0-/-Pr)3-catalyzed reactions, especially with cyclohexene and 3,4-dihydropyran. Cyclohexene was oxidized to 2-cyclohexen-l-one, and 3,4-dihydropyran gave 5,6-dihydro-4-pyrone and 5,6-dihydro-2-pyrone, albeit in yields below 8 % 59). 

In an attempt to further elucidate the mechanism of this process, these workers monitored the reaction between propiophenone enolsilane and fumaroylimide by in situ infrared (IR) spectroscopy, Scheme 25 (240). In the absence of alcoholic additives, the accumulation of an intermediate is observed prior to appearance of product. When i-PrOH is introduced, immediate decomposition of the intermediate occurs with concomitant formation of product. Evans suggests that the intermediate observed in this reaction is dihydropyran (374). Indeed, this reaction may be viewed as a hetero-Diels-Alder cycloaddition followed by alcohol induced decomposition to the desired Michael adduct. That 374 may be acting as a competent inhibitor was suggested by an observed rate reduction when this reaction was conducted in the presence of IV-methyloxazolidinone. 

A more useful way of reducing esters to ethers is a two-step procedure applied to the reduction of lactones to cyclic ethers. First the lactone is treated with diisobutylaluminum hydride in toluene at —78°, and the product - a lactol - is subjected to the action of triethylsilane and boron trifluoride etherate at —20° to —70°. y-Phenyl-y-butyrolactone was thus transformed to 2-phenyltetrahydrofuran in 75% yield, and 5-lactone of 3-methyl-5-phenyl-5-hydroxy-2-pentenoic acid to 4-methyl-2-phenyl-2,3-dihydropyran in 72% yield [1034]. 

Azadienes of this sort were studied simultaneously by Mariano et al., who reacted mixtures of (1 ,3 ) and (1E, 3Z)-l-phenyl-2-aza-l,3-pentadiene 275 with several electron-rich alkenes, e.g., enamines and enol ethers (85JOC5678) (Scheme 61). They found the (l ,3 )-stereoisomer to be reactive in this process affording stereoselectively endo 276 or exo 277 piperidine cycloadducts in 5-39% yield, after reductive work-up with sodium borohydride. The stereochemistry of the resulting adducts is in agreement with an endo transition state in the case of dienophiles lacking a cis alkyl substituent at the /8-carbon (n-butyl vinyl ether, benzyl vinyl ether, and 1-morpholino cyclopentene), whereas an exo transition state was involved when dihydropyrane or c/s-propenyl benzyl ether were used. Finally, the authors reported that cyclohexene and dimethyl acetylenedi-carboxylate failed to react with these unactivated 2-azadienes. 

The construction of the heterocycle 3 started with enantiomerically-pure ethyl lactate. Protection, reduction and oxidation led to the known aldehyde 6. Chelation-controlled allylation gave the monoprotected-diol 7. Formation of the mixed acetal with methacrolein followed by intramolecular Grubbs condensation then gave 3. The dihydropyran 3 so prepared was a 1 1 mixture at the anomeric center. 

Reductive cleavage of 5,6-dihydropyranes. The allylic ether bond of 5,6-dihydro-... 

Dihydropyrans are also a convenient source of tetrahydropyrans and full experimental details are available for the reduction of the unsubstituted dihydropyran over Raney nickel (550SC(3)794). 

The dianion derived from but-2-ynoic acid reacts with aldehydes to give 5-hydroxyalk-2-ynoates (539). Partial reduction over a Lindlar catalyst and acid-catalyzed cyclization of the resulting enoate gives the dihydropyran-2-one (78LA337). The route is exemplified by the synthesis of the naturally occurring massoia lactone (Scheme 200). In previous work (46JCS954) the hydroxyalkynoic acids themselves, obtained from epoxides and acetylene, were used. 

Usually, 3- and 4-substituted thianes are prepared from the 3- and 4-oxothians by the common techniques applicable to alicyclic chemistry. Reduction affords alcohols which may be etherified or halogenated, while oximation and reduction produces the amino derivatives, which are also accessible via the halo compounds. 2-Alkoxy and 2-alkylthio compounds are made by acid catalyzed addition of alcohols and thiols to 3,4-dihydro-2H-thiopyran (75MI22502) in a reaction analogous to the use of dihydropyran for protection of alcohols as THP ethers. 

Illustrative examples of cleavage reactions of /V-arylbenzylaminc derivatives are listed in Table 3.25. Aromatic amines can be immobilized as /V-bcnzylanilincs by reductive amination of resin-bound aldehydes or by nucleophilic substitution of resin-bound benzyl halides (Chapter 10). The attachment of the amino group of 5-aminoin-doles to 2-chlorotrityl chloride resin has been reported [486]. Anilines have also been linked to resin-bound dihydropyran as aminals [487]. 

The reaction of 2-methyl-3-trimethylsilyloxy-2//-5,6-dihydropyran with dibromocarbene (Equation 42) to give 4-bromo-2-methyl-6,7-dihydrooxepin-3(2//)-one and catalytic reduction of the latter (H2-Pd/C) to corresponding oxepanone should be mentioned. An analogous transformation is used to prepare an intermediate in the synthesis of zoapatanol <1994TL3085>. 

One of the most reactive 1,3-dicarbonyl compounds used in the domino-Knoevenagel-hetero-Diels-Alder reaction is N,N-dimethyl barbituric acid 2. It has been shown that the fairly stable products can easily been transformed into other compounds via a reduction of the urea moiety with DIBAL-H [20]. Thus, reaction of 30 with DIBAL-H at 78 °C led to 46, which can be hydrolyzed to give 47 (Scheme 5.9). In a similar way, 48 was transformed into 50 via 49 and 12 to 52 via 51. The obtained compounds containing a lactone and an amide moiety can again be further transformed using DIBAL-H followed by an elimination. In this way, dihydropyran 54 is obtained from 50 via 53 as one example. 

Hayakawa, H. Miyashita, M. An efficient and stereoselective construction of the C(9)-C(17) dihydropyran segment of swinholides A-C via a novel reductive cleavage of an epoxy aldehyde. Tetrahedron Lett. 2000, 41, 707-711. 

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