Tetrahydropyranyl ethers, synthesis

The principal variations on the normal crown synthesis methods were applied in preparing mixed crowns such as those shown in Eq. (3.55) and in forming isomers of the dibinaphthyl-22-crown-6 systems. The latter has been discussed in Sect. 3.5 (see Eq. 3.21) . The binaphthyl unit was prepared to receive a non-naphthyl unit as shown in Eq. (3.57). Binaphthol was allowed to react with the tetrahydropyranyl ether or 2-chloroethoxyethanol. Cleavage of the THP protecting group followed by tosyla-tion of the free hydroxyl afforded a two-armed binaphthyl unit which could serve as an electrophile in the cyclization with catechol. Obviously, the reaction could be accomplished in the opposite direction, beginning with catechol". ... 

Synthesis of 16,16-dimethyl-trans-A -PGEi 2.35 g of the bis-tetrahydropyranyl ether were dissolved in 6 ml of tetrahydrofuran and 60 ml of 65%-acetic acid aqueous solution and the solution stirred at 60°C to 70°C for 20 minutes. The reaction mixture was extracted with ethyl acetate, and the organic layer was washed with water, dried and concentrated under reduced pressure. The residue was purified by column chromatography on silica gel using ethyl acetate-cyclohexane (2 3) as eluent to yield 270 mg of the title compound. 

Yu, Q.S. Lu, B.Y (1994) Total Synthesis of Racemic Physostigmine, Physovenine and its Sulfur Analog by the Oxindole-5-O-tetrahydropyranyl Ether Route. Heterocycles, 39, 519-525. 

Although alcohols are oxidized by tetra-n-butylammonium persulphate when the reaction is conducted in dichloromethane, tetrahydropyranyl ethers have been produced (>90%) when attempts to oxidize the alcohol are conducted in tetrahydro-pyran (see Chapter 10) [ 19], Tetrahydrofuranyl ethers have been prepared by an analogous method [20,21 ]. Base-mediated elimination of halo acids from P-halo alcohols under phase-transfer catalysed conditions produce oxiranes in high yield (70-85%). The reaction has particular use in the synthesis of epihalohydrins from p,y-dihalo alcohols [22],... 

Krabbe SW, Angeles VV, Mohan RS (2010) Bismuth(III) bromide in organic synthesis. A catalytic method for the allylation of tetrahydrofuranyl and tetrahydropyranyl ethers. Tetrahedron Lett 51 5643-5645... 

The analogue in which carbon replaces oxygen in the enol ring should of course avoid the stability problem. The synthesis of this compound initially follows a scheme similar to that pioneered by the Corey group. Thus, acylation of the ester (7-2) with the anion from trimethyl phosphonate yields the activated phosphonate (7-3). Reaction of the yhde from that intermediate with the lactone (7-4) leads to a compound (7-5) that incorporates the lower side chain of natural prostaglandins. This is then taken on to lactone (7-6) by sequential reduction by means of zinc borohydride, removal of the biphenyl ester by saponification, and protection of the hydroxyl groups as tetrahydropyranyl ethers. 

A recently published full account of another synthesis [69] of the same alkaloid starting from the /rans-cinnamic ester 264 represented a different approach (ACD -> ACDB) to ( )-lycorine (Scheme 42). An intramolecular Diels-Alder reaction of 264 in o-dichlorobenzene furnished the two diastereomeric lactones 265 (86%) and 266 (5%) involving the endo and exo modes of addition respectively. The transposition of the carbonyl group of 265 to 267 was achieved by reduction with lithium aluminium hydride, followed by treatment of the resulting diol with Fetizon s reagent, which selectively oxidised the less substituted alcohol to give isomeric 5-lactone 267. On exposure to iodine in alkaline medium 267 underwent iodolactonisation to afford the iodo-hydroxy y-lactone 268. The derived tetrahydropyranyl ether... 

Because of problems encountered in the removal of the prop-l-enyl group in the above synthesis of the mannosyl-phosphatidylinositol, Shvets et al. [295] investigated the formation of the mono-tetrahydropyranyl ethers of the racemic inositol derivatives (429) and (430) and separated the isomeric mono-tetrahydropyranyl ethers from both by chromatography. Although the 1 -O-tetrahydropyrany 1 ether preponderated in... 

Corey and Yamamoto 233) used the P-oxido synthesis 2341 of trisubstituted olefins for the preparation of the acyclic sesquiterpene famesol 433. In this preparation the isoheptenylphosphonium salt 430 is converted into the hydroxyfamesol derivative 432 by reaction with the tetrahydropyranyl ether — protected hydroxy aldehyde 431 and formaldehyde 205. 432 is converted into famesol 433 via several steps. Other reactions of432 likewise proceeding via several steps lead to 434 which is a positional isomer of a C17-juvenile hormone 233) (Scheme 75). 

Tufariello and Tegeler18 have described a high-yield synthesis of the quinoliz-idine (11) by cycloaddition of nitrone (9) and the a/3-unsaturated ester (10) and then reduction (Scheme 1). The ester (10) was prepared conveniently from but-3-en-l-ol by ozonolysis of the tetrahydropyranyl ether followed by a Wittig reaction on the resultant aldehyde. The quinolizidine (11) was converted into lupinine (12) by a conventional procedure. 

The structure of baloxine (236) has been confirmed by partial synthesis from vindolinine,110 which has previously been converted into 19-hydroxytabersonine (237). The tetrahydropyranyl ether (238) of the (19.S)-epimer, on hydroboration-oxidation, gave a mixture of C-14 epimeric alcohols (239) on oxidation and removal of the tetrahydropyranyl ether grouping, these gave baloxine (236) (Scheme 34). Its formulation as (19S)-hydroxy-14-oxovincadifformine is thus confirmed. 

Metalatlon of 2-alkynyl and 1,2-alkadienyl tetrahydropyranyl ethers furane synthesis. /-Butyllithium metalates the lithium alkoxide 1 to afford the allenyllithium compound a quantitatively. This anion reacts with alkyl halides or CH3OH to afford 2. Another metalation-alkylation protonation sequence proceeds via b to afford 3. Hydrolysis of the latter intermediate affords furanes directly. The overall sequence can be performed in one pot from a propargyl tetrahydropyranyl ether, r-butyl-lithium, and an aldehyde. ... 

The tricyclic alcohol (130) is an intermediate in the synthesis of rimuene. Hydroboronation of its tetrahydropyranyl ether and then oxidation with iodine and lead tetra-acetate afforded the 6—18 ether which could be cleaved and oxidized to a keto-acid. Such derivatives might form suitable intermediates for the synthesis of the rosane lactones. O-MethyI-14-methyl podocarpic acid has been synthesized "" by a conventional ring a + ring c route. 

To use diastereomer [38] of [37] for synthesis of [41], a different sequence was required. As for [37], ester [38] was first converted to the tetrahydropyranyl ether [41]. The stereochemistry was corrected by esterification aiui THP cleavage to give benzoate [42], in the same stereo-... 

Double dehydrohalogenations have been used recently in the synthesis of a number of bis(methylene)triangulanes (Table 5). Typically, the starting dihalides are prepared by a sequence of cyclopropanation with chloromethylcarbene and monodehydrochlorination, in which a tetrahydropyranyl ether serves as the source of the bromide or iodide moiety (see Section 5.2.2.1.1.1.). The double elimination is carried out with potassium ier/-butoxide in dimethyl sulfoxide at or near room temperature, and gives low to moderate yields of bis(methyl-ene) products. In some cases mixtures of diastereomers were obtained due to the lack of stereospecificity of the preceding carbene addition to the double bond which consequently led to the presence of a mixture in the starting material. The procedure is illustrated by the synthesis of 1,4-bis(methylene)spiropentane (2). ... 

The total synthesis of milbemycin-p developed by Williams et al. [124] involves construction of three units the spiroketal moiety (A), carbon chain with a remote chiral centre at C-12 (B) and the substituted benzoic acid (C). Unit (A) is prepared starting from citronellol (154), while unit (B) was prepared starting from (-)-(3S)-citronellal (162) (Scheme 20). A and B were joined after transmetalation of the tetrahydropyranyl ether 166 to give 167 (Scheme 21), which is allowed to react with the aldehyde A to give 168. Further steps are shown in scheme 22. 

Methods for forming carbon-carbon bonds at the anomeric position of cyciic ethers are important processes in organic synthesis. We have shown how iactols and their derivatives can be readiiy converted into the corresponding 2-benzenesuifonyi cyclic ethers.3> These versatile intermediates can then be transformed into the corresponding dihydropyrans. 2-substituted dihydropyrans, spiroacetais, and tetrahydropyranyl ethers (Scheme 1). 

S-Hydroxytabersonine (108), in another series of transformations, has been used in a partial synthesis of baloxine (352), an alkaloid of Melodinus balansae. Protection of the hydroxyl group in 108 as its tetrahydropyranyl ether 353, followed by regiospecific hydroboration-oxidation, gave a mixture of epimeric C-14 alcohols (354) that, on oxidation and removal of the tetrahydropyranyl group, gave baloxine (352), whose structure as 19S-hydroxy-14-oxovincadifformine is thus confirmed (241) (Scheme 17). 

Since the blossom oil of lily of the valley is not commercially available, the perfumers have to rely on synthetic substitutes, such as hydroxy-citronellal (1), Lilial (3) and Bourgeonal (6) to create their muguet fragrances. The oldest lily of the valley odorants, hydroxycitronellal and cyclamen aldehyde (2) (Winthrop Chem. Corp., 1929), were discovered by chance. Serendipity still continues to play an important role. Anselmi et al. (1992) synthesized and organoleptically screened a series of 38 tetrahydropyranyl ethers. This class of compounds was chosen because of their ease of synthesis and purification, and because of their stability in alkaline media, conditions under which aldehydes tend to undergo aldol condensations. Two compounds (24 and 25) were described as having a white, floral odour reminiscent of hydroxycitro-... 

This sequence has obvious application to synthesis of resin acids and was used in fact as a key step in a synthesis of methyl desisopropyldehydroabietate (20) by Spencer et al Thus reductive carbomethoxylation of the tetrahydropyranyl ether (1 Sf gave the desired product in 68% yield (simple reduction also occurs). 

---