With dihydropyran

In other work, sulfone chemistry plays an integral part of the syntheses of both -carotene and vitamin A by workers at Kuraray. In this approach, the anion of C q P-cyclogeranyl sulfone (36) is condensed with the C q aldehyde (37). The resulting P-hydroxy sulfone (38) is treated with dihydropyran followed by a double elimination to yield vitamin A acetate. Alternatively, the P-hydroxy sulfone (38) can be converted to the 5-halo sulfone (39) and a similar double elimination scheme is employed (23,24) (Fig. 8). 

As chemists proceeded to synthesize more complicated stmctures, they developed more satisfactory protective groups and more effective methods for the formation and cleavage of protected compounds. At first a tetrahydropyranyl acetal was prepared, by an acid-catalyzed reaction with dihydropyran, to protect a hydroxyl group. The acetal is readily cleaved by mild acid hydrolysis, but formation of this acetal introduces a new stereogenic center. Formation of the 4-methoxytetrahy-dropyranyl ketal eliminates this problem. 

The THP derivative of the imidazole nitrogen in purines has been prepared by treatment with dihydropyran (TsOH, 55°, 1.5 h, 50-85% yield). It is cleaved by acid hydrolysis. ... 

The hindered 11 )5-hydroxyl group fails to react with dihydropyran. However, mixed acetals [e.g., methoxymethyl ether (97)] and hemiacetals e.g., hydroxymethyl ether (98)] are obtained as by-products in the formation of the BMD group. ... 

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... 

In addition to its other properties, interest in the potential use of the vasodilative properties of prostaglandin El, alprostadil ( ), has led to several conceptually different syntheses.For this purpose, the classic Corey process has to be modified by reversing the order of addition of the side chains to allow for convenient removal of the unwanted double bond in the upper side chain. For example, Corey lactone is protected with dihydropyran (acid catalysis), reduced to the lactol with diisobutyaluminum hydride, and then subjected to the usual Wittig reaction to give intermediate This is... 

In contrast to alkoxycarbene complexes, most aminocarbene complexes appear too electron-rich to undergo photodriven reaction with olefins. By replacing aliphatic amino groups with the substantially less basic aryl amino groups, modest yields of cyclobutanones were achieved (Table 10) [63], (Table 11) [64]. Both reacted with dihydropyran to give modest yields of cyclobutanone. Thio-carbene complexes appeared to enjoy reactivity similar to that of alkoxycar-benes (Eq. 15) [59]. 

Triazolines from the cyclic enol ethers, dihydrofuran and dihydropyran, decompose at 100-130° into anils and nitrogen. Thus p-bromophenyl azide reacts with dihydropyran (69) to give triazoline 70 which decomposes thermally into the aryl-inline of 5-valerolactone (71). Photochemical decomposition of 70, on the contrary, yields 7-p-bromophenyl-7-aza-2-oxabi-cyclo[4.1.Q]heptane (72) in 67% yield. Scheiner has shown that aziridine 72 is stable at the decomposition temperature of 70, proving that it is not an intermediate in the thermal conversion of 70 to 71. 51... 

Brown and Edwards have studied the photochemical reaction of ethyl azidoformate with dihydropyran and have isolated in good yield the very reactive aziridine 115. The thermal reaction between the two compounds, however, takes a completely different course via triazoline to imino lactone. 

Acetalation with Enol Ethers Under Kinetically Controlled Conditions. The first mention of the use of an enol ether to protect the hydroxyl group of an alcohol was developed by Paul [46], who introduced the reaction with dihydropyran to give tetrahydro-pyranyl ethers, which is still used 60 years later. In spite of some noticeable developments, such as the preparation of 2 3 -0-aIkylidene derivatives of nucleosides [33] the synthesis of 4,6-O-ethylidene-a-D-glucopyranoside with use of methylvinylether [47] the intra-... 

For cyclopropanation of very electron-rich alkenes such as vinyl ethers copper(II) trifluoroacetate, copper(II) hexafluoroacetylacetonate or rhodium(II) acetate are the catalysts of choice. Copper trifluoroacetate catalysed cyclopropanation of vinyldia-zomethane with dihydropyran gives the corresponding vinyl cyclopropane adduct in low yield (equation 17). In contrast, catalytic decomposition of phenyldiazomethane in the presence of various vinyl ethers results in high-yield phenylcyclopropane formation (equations 18 and 19)27. 

Tetrahydropyranylation The reaction of an alcohol (even tertiary) with dihydropyran is catalyzed efficiently by [(CH3)3Si0]2S02. The resulting ether is isolated in 90-100% yield by addition of pyridine and concentration of the solvent. The sulfate also catalyzes alcoholysis of the derivative at 25° (10-90 minutes). It is also useful in some transesterifications. 

Aldol-type reaction of acetals with alkenes. Mildly activated alkenes can undergo addition reactions with acetals in the presence of ClSi(CH3)3 and SnCl2, as in the reaction with dihydropyran. However, the corresponding reaction with styrene requires a full equivalent of ClSi(CH3)3 and a catalytic amount of SnCl2 for a satisfactory yield. 

Tetrahydropyranylation of tert-alcohols.2 The reaction of ten-alcohols with dihydropyran in CH2C12 at 0° catalyzed by this reagent provides tetrahydropyranyl ethers in 78-96% yield. 

One method that has found widespread use for the protection of an alcohol is reaction with dihydropyran to form a tetrahydropyranyl ether. Once the desired reaction has been accomplished, the protecting group can be removed by treatment with aqueous acid or acid and ethanol. The formation of a tetrahydropyranyl ether and its cleavage are illustrated in the following equation ... 

Ethoxycarbonyl-5-phenyl-l//-pyrrole-2,3-dione (a dioxopyrroline) undergoes head-to-tail regiochemical photocycloaddition with dihydropyran to give the cis-syn-trans adduct (21) in 19% yield (Equation (2)) <90CPB370>. The structure and stereochemistry of this product, which arises via a [7t2s + 7t2a] process in an endo encounter complex, was determined by x-ray analysis. 

Treatment of the monochloro diethylene glycol 9 with dihydropyran yields the protected alcohol 10. Reaction of 2,2, 2"-triaminotriethylamine (tren) 11 with toluenesulfonyl chloride gives the tritoluenesulfonyl derivative 12. The pyranyl ether 10 may be condensed with the tris(sodium) salt of 12 leading to 13. Removal of the tetrahydropyranyl group is achieved in high yield under... 

In many instances the reaction of an alcohol with dihydropyran (or ethyl vinyl ether or 2-methoxypropene) does not go to completion despite the addition of a large excess of the enol ether as much as 20% of the starting material will be present at equilibrium. The equilibrium, once reached, can be shifted toward product by adding excess finely powdered anhydrous potassium carbonate and stirring the reaction mixture at room temperature. As the acid concentration gradually diminishes, the reaction goes to completion. 

An acidic solution of 2,4-dinitrophenylhydrazine reacts with N-p-chlorophenyl-sulfonyl-3-ethoxy-l,2-thiazetidine 1-oxide to give (80%) the bis-2,4-dinitrophenyl-hydrazone of glyoxal. The adduct of A-sulfinyl-p-chlorophenylsulfonamide with dihydropyran is inert to catalytic hydrogenation and bromination. Treatment of two l,2-thiazetidine-3-one 1-oxides (e.g., 421) with hydriodic acid results in ring-cleavage and loss of sulfur. They are not oxidized to 1,1-dioxides by peracetic acid, ° but m-chloroperbenzoic acid accomplishes this oxidation. The unstable adducts with ketene decompose to amides with loss of hydrogen sulfide and sulfur dioxide or may be trapped by reaction with aromatic amines as shown for thiazetidine 1-oxide 422.An aldol-type condensation has been reported for A -cyclohexyl-1,2 thiazetidine-3-one 1-oxide and p-(A(A"-dimethylamino)benz-aldehyde. " Sulfur monoxide is lost in the flash-vacuum thermolysis of 422a. ... 

---