Tetrahydro-2- pyrane

DOPS dimeihyl[ 1,1 -dimethyl-3-(tetrahydro-2//-pyran-2-y loxy )propy 1] silyl... 

Schlosser generated dimethyl [( )-l-(tetrahydro-2//-pyran-2-yloxy)-2-butenyl]boronate (1) via metalation of l-(tetrahydro-2//-pyran-2-yloxy)-2-butene at — 75 °C followed by treatment of the allylic anion with fluorodimethoxyborane13. 

The addition of (Z)-3-(alkylamino)-2-butenoic acid esters to nitroalkenes derived from open-chain sugars gave a 50 50 mixture of diastereomeric products 32. The reaction of chiral 2-sub-stituted l-(2-nitroethenyl)pyrrolidines with zinc enolates of 3-substituted tetrahydro-2//-pyran-2-oncs in 1,2-dimethoxyethane at — 78 °C afforded the corresponding 3,3-disubstituted products in 82-96% ee via an addition-elimination process33. The stereochemical course of the reaction was determined by chemical correlation of (S)-( )-3-ethyltetrahydro-3-(2-ni-troethenyl)-2//-pyran-2-one with ( + )-quebrachamine. 

The addition of the lithium enolates of various acetic add esters to (S)-3-(4-methylphcnyl-sulfmyl)-2(5//)-liiranone and (,S)-5,6-dihydro-3-(4-methylphenylsulfinyl)-2//-pyran-2-one gives, after desulfurization with Raney nickel, 4-substituted dihydro-2(3//)-furanoncs and 4-substituted tetrahydro-2//-pyran-2-ones, respectively, in good to quantitative enantiomeric excess. Addition of the enolate occurs via the nonchelate mode. The enolate of methyl (phenylthio)acetatc is best overall in regards to chemical yields and enantiomeric purity of the final lactone product13. 

C2oH fiClNO 149968-10-5) see Montelukast sodium [tx5-( )]-3-[2-(7-chloro-2-quinolinyl)ethenyl]-a-[2-[2-(l-methyl-l-[(tetrahydro-2//-pyran-2-yl)oxy]ethyl]phenyll-ethyl]benzenemethanol methanesulfonate (ester) (CjjHjgClNOjS 162489-71-6) see Montelukast sodium (5)-a-[3-[(E)-2-(7-chloro-2-quinolinyI)ethenyl]phenyl]-2-(l-hydroxy-l-methylethyl)benzenepropanol (C2i,H2xClN02) see Montelukast sodium (5)-a-[3-[( )-2-(7-chloro-2-quinolinyl)ethenyl]phenyl]-2-(l-hydroxy-l-methylethyl)benzenepropanol methanesulfonate... 

Either enantiomer of a-alkylated alkanoic acids, 3-substituted dihydro-2(3//)-furanones and 3-substituted tetrahydro-2//-pyran-2-ones with known absolute configuration and high optical purities can be obtained from metalation and alkylation of chiral 4,5-dihydrooxazoles (see Section 1.1.1.4.3.). 

A mixture of 128 (12.3 g, 29 mmol) and 6 M NaOH (148 mL) in 95% EtOH (155 mL) was stirred at rt for 48 h. The mixture was concentrated in vacuo to remove most of the EtOH and the residue was extracted (Et20). The Et20 extract was dried and concentrated in vacuo. The residue was chromatographed (EtOAc/hexane containing 2% TEA 1 1) to give (2 )-4-benzyl-5-(tetrahydro-2//-pyran-2-yloxy)pent-2-enamine as a thick pale yellow oil yield 5.3 g (66%) Rf 0.45 (2% TEA in EtOAc/hexane 1 1). 

Dihydro-2//-pyran (1.11 g, 13.2mmol) was added dropwise to a stirred solution of benzenesulfinic acid (1.88 g, 13.2 mmol) in dry dichloromethane at room temperature under argon. Stirring was continued for 2h, then the solvent was removed under reduced pressure and the product recrystallized from diethyl ether/petroleum to give 2-(benzenesulfonyl)tetrahydro-2//-pyran (1) (2.45 g, 82%) as white needles, m.p. 78°C. 

CmH NOjSSi 106560-32-1) see Faropenem sodium 11A- 1 (4A, 6A ),2 -,bp,8P,8aa]l-4-[ (1,1-dimethyl-ethyl (dimethylsilyl (oxy -6- 2-( 1,2,6,7,8,8a-hexahydro-8-hydroxy-2,6-dimethyl-l-naph thalcnyl)ethyl]tetrahydro-2//-pyran-2-one... 

C4HK02 86087-23-2) see Amprenavir 2-[2(R)-hydroxy-3-f(tetrahydro-2//-pyran-2-yl)oxy]-l(lS)-(phcnylmethyl)propyl]-l//-isoindolc-13(2/f)-dione (C25H25NO5) see Saquinavir 5-hydroxy-l,2,3,4-tetrahydroquinolin-2-one (C,H9N02 30389-33-4) see Cartcolol... 

C,HnNO 3731-38-2) see Clidinium bromide (3R)-6-oxo-3-r(tetrahydro-2//-pyran-2-yl)oxy)hexanoic acid ethyl ester... 

The cydization of unsaluraled alcohols mediated by acids has only seldom been utilized for the syntheses of tetrahydro-2//-pyrans, and stereocontrol is generally reached through equilibration, owing to the reaction conditions. Thus, in the presence of sulfuric acid, ( )-3,7-dimethyI-5,7-octadien-l-ol (1) affords a 91 9 (cis/trans) mixture of the 2,4-disubstituted tetrahydro-2/7-pyrans in almost quantitative yield. The diequatorial 2,4-cis relationship is preferred which relies on thermodynamic control of the cydization67-68. 

Alkadienols can also be cyclized with silver nitrate in acetone/water and the corresponding 2,4-disubstituted tetrahydro-2//-pyrans are recovered in good yield. The civ-isomer is the major component of the reaction mixture, as determined by GLC analysis, and its configuration is assigned on the basis of H-NMR data69. 

Treatment of secondary 5-alkenoIs with mercury(II) acetate or mercury(II) trifluoroacetate in tetrahydrofuran under thermodynamic conditions results in 2,6-disubstituted tetrahydro-2/7-pyrans in good yield. The stereochemical outcome of the reaction is such that the tetrahydro-2//-pyrans with the substituents in the favored 2,6-diequatorial orientation are preferentially... 

The halocyclization of cyclic unsaturated alcohols to give fused 2,6-disubstituted tetrahydro-2//-pyrans proceeds quite predictably since the equatorial disubstituted isomer is generally formed whenever possible. The yields arc moderate to good and (V-iodosuccinimide and iodine have been employed as halonium sources. When the cyclization is performed under kinetic control with vV-iodosuccinimide in dichloromethane, and a tertiary carbocation is the intermediate in the reaction, electronic factors are responsible for tetrahydro-2//-pyran ring formation76. 

On the contrary, when electronic facLors are lacking, the cyclization to a six-membered ring can be realized under thermodynamic conditions by the use of iodine in acetonitrile, and the more stable 2,6-m-disubstitutcd tetrahydro-2//-pyran is obtained in good yield. The reaction proceeds with total stereoselectivity and the structure of the unique isomer recovered from the reaction mixture is assigned on the basis of H-NMR data76. 

Fused tetrahydro-2//-pyrans can also be obtained in high stereoseleclivity by oxythallation. In fact, starting from /ra .v-2-[( )-2-methyl-2-butenyl]cvclohexanol (7), tetrahydro-2//-pyran formation proceeds via initial cyclization to the tetrahydrofuran, followed by ring expansion, giving the /ra/z.v-6,6-fused product 8 in 50% isolated yield13. 

Few examples are reported for the cyclization of 5-alkenols to 2,3-disubstituted tetrahydro-2//-pyrans where the stereoselectivity depends on the nature of the allylic substituent. The cyclization of 4-methyl-5-hexen-l-ol (1), performed with phenylselenyl triflate in dichloromethane at — 78 "C, proceeds with low 1,2-asymmetric induction and the corresponding tetrahydro-2//-pyran 2 is recovered in 85% yield as a 66 34 (Ircms/cis) diastereomeric mixture19. 

S, 4/J,5/J,6,S)-3,4,5-Tris(benzyloxy)-2-benzyloxyniethyl-6-[(chloroniercurio)niethyl]tetrahydro-2//-pyran (8) Typical Procedure79 ... 

Cyclization of the 4,5-dihydroisoxazole 1 with iodine in refluxing dichloromethane gives the corresponding tetrahydro-2//-pyran 2 in 82 % yield. The reaction proceeds with high 1,3-asymmetric induction and the ww-2,6-disubstituted isomer is the predominant component of the reaction mixture, although the reason for this selectivity is unclear38. 

Moreover, cyclization of(Z)-2-methyl-5-octen-l-ol (3) leads mainly to the 2.5-rran.s-disubstituted tetrahydro-2//-pyran with high 1,4-asymmetric induction and the diequatorial arrangement is preferred81. 

When three substituents are present in the tetrahydro-2//-pyran ring, they lie in the equatorial orientation and the 2,5-fraw.v-2,6-c7.s-isomer is the preferred isomer81. 

Diastereoselective Synthesis of 2,6-Disubstituted Tetrahydro-2//-pyrans via Alkoxycarbonylation of Alkenols... 

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