2,6-Disubstituted 3,6-dihydro-27/-pyrans

Aside from the ready preparation of some a,p-disubstituted cyclopentanones, the utility of the cyclopropanone hemiacetal approach has been illustrated by the total synthesis of the methyl ester of 11-deoxyprostaglandin E2 342 15). Towards this end, 1-trimethylsilylbutadiynylcyclopropanol 13, readily available from the cyclopropanone hemiacetal 3 (vide supra, Sect. 2.1, Eq. (6)) was successively treated with dihydro-pyran in CH2C12 in the presence of 10% mol. equiv. of PPTS 101). Desilylation by potassium fluoride in DMF 138), formation of the lithium salt with n-BuLi and condensation with hexanal gave the propargylic alcohol 339 in 64 % overall yield. The... 

The application of RCM to dihydropyran synthesis includes a route to 2,2-disubstituted derivatives from a-hydroxycarboxylic acids. In a one-pot reaction, the hydroxy esters undergo sequential O-allylation, a Wittig rearrangement and a second O-allylation to form allyl homoallyl ethers 8. A single RCM then yields the 3,6-dihydro-2//-pyran 9. The process is readily adapted not only to variably substituted dihydropyrans but also to 2-dihydrofuranyl and 2-tetrahydrooxepinyl derivatives and to spirocycles e.g. 10 through a double RCM (Scheme 4) <00JCS(P1)2916>. 

Disubstituted dihydropyrans are produced with high u/iri-selectivity when 2-phenyl-4-(4-tolylsulfonyl)-3,4-dihydro-2H -pyrans ate treated with Al-based Lewis acids <99SL132>. Tetraenes 10, derived from dienes via their epoxides, undergo a double RCM reaction under Ru-catalysis to yield polycyclic ethers 11 in which the dihydropyran units can be joined by a variable number of carbon atoms <99JOC3354>. Continued work on the use of dispiroketals in synthesis has led to an improved route to the enantiomers of bi(dihydropyrans) 12 <99JCS(P1)1639>. 

New possibilities in hetero-Diels-Alder condensation have been opened by the introduction of highly active l-methoxy-3-trimethylsilyloxy-, 4-benzoyIoxy-l-methoxy-3-trimethylsilyloxy-, and 2-acetoxy-l-alkoxy-3-trimethylsilyloxy-l,3-butadienes ( Danishefsky dienes, 5). These compounds readily react under atmospheric pressure, in the presence of Lewis acids, with normal aldehydes (e.g., acetaldehyde, benzaldehyde, furfural) to furnish 2,3-disubstituted or 2,3,5-trisubstituted derivatives of 2,3-dihydro-4H-pyran-4-one 7 capable of readily functionalizing to sugars (Scheme 5) [26]. This approach... 

These complexes can also be used to prepare optically pure cis-2,5-disubstituted 5,6-dihydro-2tf-pyrans such as 3 by using a molybdenum nitrosyl allyl complex as an intermediate. 

Alkoxy-3,4-dihydro-2//-pyrans are converted to 4,5-ar-disubstituted tetrahydrofuranones upon epoxidation and subsequent oxidation <2006TL1617, 2006MOL959>. 

Hansson, S, Miller, J F, Liebskind, L S, Synthesis and reactions of enantiomerically pure molybdenum rr-complexes of 2H-pyran. A general approach to the enantiospecihc synthesis of cA-2,5-disubstituted-5,6-dihydro-2H-pyrans and cA-2,6-disubstituted tetrahydropyrans, J. Am. Chem. Soc., 112, 9660-9661, 1990. 

TV-Substituted 2-oxo-jV-(2-propenyl)-2//-pyran-6-carboxamides underwent spontaneous IMDA reaction under the conditions employed for their formation from TV-substituted 2-propenylamines and 2-oxo-2//-pyran-6-carbonyl chloride44. The products 19 were converted in almost quantitative yield on gentle heating to 2,4-disubstituted 2,3-dihydro-l//-isoindol-l-... 

Disubstituted 5,6-dihydro-2//-pyranes can be prepared stereoselectively utilizing the Lewis-acid catalyzed cyclization of vinylsilanes carrying an acetalized glyoxylic ester functionality in P-position [18]. Interestingly, the geometry of the double bond in the educt controls the stereochemistry in the products 10/11 ... 

Disubstituted quinolines of type 21 were obtained from acetylenic ketones 2 as a result of a condensation reaction with 2-amino thiophenol 19 followed by sulfur extrusion (entry f). Acetylenic ketones have also been employed as dienophiles in Carbonyl-Alkyne-Exchange (CAE) reactions with dienes 22 (derived from 2,2-dialkyl-2,3-dihydro-4//-pyran-4-ones )(entry g) or 24 (entry h) to yield aromatic compounds 23 and 25 in a highly regioselective way. 

The HDA reaction features in a diastereoselective synthesis of c/j-2,6-disubstituted 5,6-dihydro-2//-pyrans, but this is based on the initial formation of a dihydropyran-4-one. Regio- and stereo- chemistry are controlled during the reduction to the pyranol and an ester enolate Claisen rearrangement completes the sequence <97AJC43>. 

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). 

Catalytic quantities of bismuth(III) triflate initiate the rearrangement of epoxides to aldehydes which then react with (Z)-5-hydroxyalkenylsilanes to give 2,6-disubstituted 3,6-dihydro-277-pyrans (Scheme 58). ... 

Disubstituted 5,6-dihydro-2H-pyrans can be prepared stereoselectively utilizing the lEwis-acid catalyzed cyclization of vinylsilanes carrying an acetalized glyoxylic ester... 

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