Acetal, 17-21, formation tetrahydropyran

Suginome, M., Iwanami, T, Ito, Y. (1998). Stereoselective Cyclization of Highly Enantioenriched Allylsilanes with Aldehydes via Acetal Formation, New Asymmetric Access to Tetrahydropyrans and Piperidines, J., Org Chem 63, 6096-6097. 

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). 

Acetals and ketals are very important protecting groups in solution-phase synthesis, but only a few constructs have been used as linkers in solid-phase synthesis (Tab. 3.3). The THP-linker (22) (tetrahydropyran) was introduced by Ellman [54] in order to provide a linker allowing the protection of alcohols, phenols and nitrogen functionalities in the presence of pyridinium toluene sulfonate, and the resulting structures are stable towards strong bases and nucleophiles. Other acetal-linkers have also been used for the attachment of alcohols [55, 56]. Formation of diastereomers caused by the chirality of these linkers is certainly a drawback. Other ketal tinkers tike... 

Cyclopropanols can be converted to various cyclopropyloxy derivatives (esters, e.g. acetates, ethers, e.g. methyl and ethyl ethers, and acetals, e.g. tetrahydropyran-2-yloxy derivatives) under the appropriate reaction conditions. In most cases the synthesis of cyclopropyl esters by the reaction between a cyclopropanol and an acid chloride (e.g. formation of 1 ) or acetic anhydride (e.g. formation of 2 ) have been reported. The yields were particularly good (84-95%) when acetic anhydride was used, although a drawback of the reaction can be byproduct formation. When a reactive moiety is attached to the cyclopropane ring in addition to the hydroxy group, other reactions can also occur m-l-(aminomethyl)-2,2-dimethyl-3-(2-methylprop-l-enyl)cyclopropanol (3) reacted with phosgene in benzene to give the corresponding carbamate l,l-dimethyl-2-(2-methylprop-l-enyl)-4-oxa-6-azaspiro[2.4]heptan-5-one (4) in 31% yield. ... 

In this section, the formation and cleavage of eight protecting groups for alcohols and phenols are presented acetate acetonides for diols benzyl ether para-methoxybenzyl (PMB) ether methyl ether methoxymethylene (MOM) ether ferf-butyldiphenylsilyl (TBDPS) silyl ether and tetrahydropyran (THP). 

Replacing the (3,y-unsaturated carbonyl group by an alkoxy group offers a different cyclization process for tetrahydropyran formation, namely simple acetalizations as shown in Equation 1.46 [44],... 

The formation of acetals, by the acid catalyzed addition of hydroxyl compounds to a,/8-ethylene ethers is a useful method of protecting the hydroxyl group in reactions effected in basic media.—E 3-Chloro-l-propanol and dihydropyran, with a few drops of coned. HC1, allowed to stand for 3 hrs. with occasional shaking —> 2-(y-chloropropoxy)-tetrahydropyran. Y 78%. (F. e. s. W. E. Parham, E. L. Anderson, Am. Soc. 70, 4187 (1948).)... 

The resin of E.foliosissima contained three carboxylic acids as the major metabolites which could be isolated more conveniently as their methyl ester derivatives. The major component was the unstable acetoxy ester (111) which displayed an allylic tertiary alcohol. Transesterification of the acetate with NaOMe, followed by heating the derived hydroxy compound in a solution of CDCI3, led to the formation of the tetrahydropyran (112). This compound proved identical to the second major metabolite isolated from the methylated acidic fraction. This interrelationship was fortunate... 

Homoallylic alcohols such as 107 (R=H) give mixtures of regioisomers 108 and 109. Both can be cycled to provide tetrahydrofiiran or tetrahydropyran derivatives (Figure 31). As in the case of allyhc alcohols, substitution in the double bond or in the allyhc carbon favors the formation of the linear aldehyde. The linear aldehyde 109 provides the hemiacetal 110, from which acetals [64], lactones [65, 77] and also enolethers such as 111, can be formed [70, 71, 72, 73]. 

Abbreviations Agg. = aggregates AcrCN = acrylonitrile DMF = V,V-dimethylformamide DMSO = dimeth-ylsulfoxide EC = ethylene carbonate HC02Et = ethyl formate Me2CO = acetone MeCN = acetonitrile MeCOsMe = methyl acetate MeTHF = 2-methyltetrahydrofuran PC = propylene carbonate THF = tetrahy-drofuran THP = tetrahydropyran. 

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