Tetrahydropyran Compounds

By use of the dithane (20) [e./., compound (4)], prepared from 4,6-dideoxy-D-xylo-hexose by thioacetalation and base-catalysed elimination, lithium 

Narahara, K. Beppu, andT. Ogawa, Jfoen Yoshishu-Tennen Yuki Kagobutsu Toronkai, 22nd, 1979, 493 Chem. Abstr., 1980, 92, 215 726). 

4-Dianhydro-2-0-toluene-p-sulphonyl-i8-D-galactopyranose has been used to prepare the lactone (23) (c./., Vol. 11, p. 228) which, by standard methods of prostaglandin chemistry, has been converted into thromboxane B2. The branch group at C-4 led to the a-chain and C-6 was extended into the CO-chain. 

A 19-step synthesis of (-)-cis-rose oxide from D-glucose involves 

Three papers report syntheses of (-)-c -multistriatin (22). Fraser-Reid s group used glycenosulose (23) to prepare the deoxy- 

Lukac s group use D-galactose to prepare the branched-chain sugar (26), introducing the branch methyl groups using lithium dimethyl cuprate on oxiran intermediates, followed by 3-deoxygenation via the xanthate ester. 

The use of D-ribose for preparing key intermediates in the synthesis of pseudomonic acids is referred to in Chapter 13 (ref.ll). Syntheses of the bicyclic unsaturated lactone (34) and its enantiomer have been developed from D- and L-arabinose respectively. 

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Tetrahydropyran Formation. The use of an appropriately substituted allylsilane with a variety of electrophiles with 10% TMSNTfa gave the cyclized tetrahydropyran compounds (eq 9). For this reaction, TMSNTf2 outperformed, variety of Lewis acids including TMSOTf, TiCU, TiCl2(Of-Pr)2, SnCLj, BF3-OEt2, and EtAlCh. ... 

Biotransformation of linalool gave both tetrahydrofurans and tetrahydropyranes, but the biotransformation of trans-nerolidol discussed above produced only tetrahydrofurans. A set of homologous dimethylalkadienes were used as substrates to be epoxidized with the fungus Diplodia gossypina. It turned out that dimethylhexa-2,4-diene 53 could not form any tetrahydrofuran probably because the second double bond could not be attacked (Fig. 8). All the other hydrocarbons like 47 and 50 formed the tetrahydrofuran derivative (49 and 52) and sometimes also the tetrahydropyrane compound, but in much lower yields. 

This synthesis came shortly after one by Prelog, Kohlberg, Cerkovnikov, Rezek and Piantanida (1937) based on a series of reactions which, with modifications and extensions. Prelog and his colleagues have applied to the syntheses of bridged heterocyclic nuclei, of which this is an example. 4-Hydroxymethyltetrahydropyran (VI R =. OH) is converted via the bromo-compound (VI R = Br) and the nitrile (VI R = CN) into tetrahydropyran-4-acetic acid of which the ethyl ester (VII) is reduced to 4-()3-hydroxyethyl)-tetrahydropyTan (VIII). This is converted by fuming hydrobromic acid into 3-(2-bromoethyl)-l 5-dibromopentane (IX) which with ammonia in methyl alcohol yields quinuclidine (V). 

Interesdng intramolecular cycllzadon of Tnitroalkyl radicals generated by one-electron oxidadon of nci-nitro anions vrith CAN is reported. As shown in Eq. 5.44, stereoselecdve formadon of 3,4-funcdonalized tetrahydroflrtans is observed. TNitro-6-heptenyl radicals generated by one electron oxidadon of aci-nitroanions vrith CAN afford 2,3,4-trisnbsdtuted tetrahydropyrans. The requisite nitro compounds are prepared by the Michael addidon of 3-buten-Tal to nitroalkenes. 

The cyclization of the homologous epoxide 36 under acidic conditions was also investigated (Table 9.5) [110]. As would be expected, compound 36a reacted by a 6-exo cyclization to give tetrahydropyran 38a (Entry 1). The a, 3-unsaturated hydroxy epoxide 36b gave a 1 3.5 mixture of oxepane 37b and tetrahydropyran 38b (Entry 2). Subjection of 36c and 36d, which both contain more electron-rich 71-systems, to the reaction conditions resulted in preferential 7-endo cyclization to give 37c and 37d, thus confirming the powerful regiodirecting effect of the vinyl moiety (Entries 3 and 4). 

In order to improve the selectivities in these reactions, styrylepoxides 39 and 40 were prepared and subjected to acid-catalyzed cyclizations (Scheme 9.23) [113]. Both compounds, however, afforded almost identical mixtures of diastereomeric oxepanes 41 and 42 (83%, dr 21 79 and 66%, dr 20 80, respectively), while no tetrahydropyran 43 was formed. Clearly, the additional stabilization provided by... 

The outcomes of intramolecular cyclizations of hydroxy vinylepoxides in more complicated systems can be difficult to predict. In a study of the synthesis of the JKLM ring fragment of dguatoxin, epoxide 44 was prepared and subjected to acid-mediated cydization conditions (Scheme 9.24) [114]. Somewhat surprisingly, the expected oxepane 45 was not formed, but instead a mixture of tetrahydropyran 46 and tetrahydrofuran 47 was obtained, both compounds products of attack of the C6 and C5 benzyl ether oxygens, respectively, on the allylic oxirane position (C3). Repetition of the reaction with dimsylpotassium gave a low yield of the desired 45 along with considerable amounts of tetrahydropyran 48. 

A three-component domino process consisting of an ene reaction followed by the addition of an allylsilane to afford polysubstituted tetrahydropyrans in generally good yield was described by Marko and coworkers [115]. However, the nature of the products formed in this process depends heavily on the Lewis acid employed as a catalyst. Thus, reaction of the allylsilane 4-333 with an aldehyde in the presence of BF3-Et20 led to the domino products 4-334, whereas in the presence ofTiCL the diol 4-332, and in the presence of Et2AlCl the alcohol 4-335, were obtained (Scheme 4.74). The latter compound can then be transformed in stepwise manner to 4-334, using the same aldehyde as previously. However, it is also possible to use another aldehyde to prepare tetrahydropyrans of type 4-336. 

Intramolecular cycloadditions of chiral nitrones provide a useful tool for the preparation of bioactive heterocyclic compounds.63 Shing et al. demonstrated that 1,3-dipolar cycloaddition of nitrones derived from 3-0-allyl-hexoses is dependent only on the relative configuration at C-2,3, as shown in Scheme 8.16. Thus 3-0-allyl-D-glucose and -D-altrose (both with threo-configuration at C-2,3) produce oxepanes selectively, whereas 3-O-allyl-D-allose and -D-man-nose (both with erythro-configuration at C-2,3) give tetrahydropyranes selectively.80... 

Tetrahydropyran (THP), aldehyde etherification, 67-68 Tetralin compounds, 5-methoxytetralin reduction of substituted naphthalene, 132-133... 

If the side chain with the nucleophile is situated in the 1-position of the conjugated diene, a palladium-catalyzed spirocyclization occurs. In this case stereoselective oxa-spirocyclizations were obtained from the diene alcohols 59 and 60 (equation 23 -25)58. The reaction worked well for the formation of a tetrahydrofuran and tetrahydropyran in the spirocyclization. In the absence of chloride ions 59 gave high yields of the acetoxy oxaspirocyclic compound 61 via a 1,4-anti addition across the diene (equation 23). In the presence of stoichiometric amounts of LiCl a 1,4-syn oxychlorination took place and allylic chloride 62 was obtained (equation 24). Under chloride-free conditions, cyclohep-tadiene alcohol 60 afforded oxaspirocyclic acetate 63 (equation 25). 

Tetrahydropyran epoxides 12, the synthesis of which involves a RCM, undergo a base-induced rearrangement to 3,4-dihydro-2//-pyran-4-ols 13. These compounds are converted stereospecifically to 3,6-dihydropyrans 14 on treatment with allyltrimethylsilane (Scheme 6) <00EJO3145>. 

Li et al.2S9 Nishikawa et al. described how an organomanganese compound could ring-open an allylic tetrahydropyran to give allylic secondary alcohols by a different mechanism.292... 

Primary and secondary alcohols are oxidized to the corresponding carbonyl compounds by tetra-n-butylammonium persulphate in dichloromethane but, when the reaction is conducted in tetrahydropyran, tetrahydropyranyl ethers (>90%) are formed by a direct one-electron oxidative reaction of tetrahydropyran with the alcohol [9]. Tetrahydrofuranyl ethers have been prepared by an analogous method (10, 11],... 

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