Alcohols, secondary, conversion into

The synthetic method was also applicable to the conversion of secondary alcohol derivatives 167 into the corresponding internal allenes 168 (Scheme 3.86). 

The combination of the preceding method of obtaining allyl alcohols with the Sharpless kinetic resolution (SKR) of secondary allyl alcohols allows conversion of the original racemic allyl alcohol into a pure enantiomer with a 100% theoretical yield. By this procedure, the glycidol obtained by the SKR epoxidation of the secondary allyl alcohol is converted into the corresponding mesylate and then treated with the Te ion, furnishing the allylic alcohol with the same configuration of the enantiomer in the SKR which... 

The solid-phase synthesis of oligosaccharides is usually performed using acid-resistant linkers and protective groups, because of the slightly acidic reaction conditions required for glycosylations (Section 16.3). Hydroxyl group protection is conveniently achieved by conversion into carboxylic esters, such as acetates, benzoates, or nitro-benzoates. Support-bound esters of primary or secondary aliphatic alcohols can be cleaved by treatment with alcoholates [97-99] (Table 7.8), with DBU in methanol, with hydrazine in DMF [100] or dioxane [101], or with ethylenediamine [102], provided that a linker resistant towards nucleophiles has been chosen. 

Substrates suitable for oxidative conversion into carbonyl compounds are alkenes, primary or secondary alcohols, and benzyl halides. Polystyrene-bound alkenes have been converted into aldehydes (with the loss of one carbon atom) by ozonolysis followed by reductive cleavage of the intermediate ozonide (Entry 1, Table 12.3). 

Conversion of saturated, primary alkyl and aryl alkyl alcohols into the corresponding aldehydes can be achieved by this method provided that the alcohols are entirely dissolved in the organic phase. Relatively unstable protective groups are not affected, as in the oxidation of the acetonide of 1,2,6-hexanetriol, whereas conjugated and isolated double bonds give rise to side reactions which considerably decrease selectivities and yields.4 Some examples of aldehydes synthesized with this method are reported in Table 1. Under the same conditions, secondary alcohols are oxidized to ketones. Addition of catalytic amounts of quaternary onium salts allows fast and total conversion of primary alcohols and aldehydes into carboxylic acids making this methodology very versatile 4... 

The hydroxyl group of a primary, secondary, or tertiary acyclic or alicyclic alcohol may be protected by conversion into (a) an ether, (b) a silyl ether, or (c) an ester. The most important method for the protection of a 1,2- or 1,3-diol is conversion into (d) a cyclic acetal. 

Ritter reaction. The original version for this conversion of a tertiary alcohol to an amide involved a reaction with nitriles in a strongly acidic medium.1 In a new version, the alcohol is converted into a triflate, which need not be isolated, but is treated with a nitrile (2 equiv.) in CH2C12 and then with aqueous NaHC03. Overall yields are 50-98%. The advantage of this version is that it is applicable to primary and secondary alcohols as well as tertiary ones.2... 

The reaction is the same as that involved in the usual chemical preparation of iodoform, whereby a colorless solution of hypoiodite (obtained by dissolving iodine in a sufficient quantity of potassium-hydroxide solution) is made to react with alcohol. The decomposition potential of potassium iodide, investigated by Dony-Henault,2 show s that the iodine as such does not act on the alcohol, but only after its conversion into hypoiodite. The iodine ions are set free at the same anode potential no matter if alcohol is added or not. The alcohol does not act as a depolarizer towards the iodine ion the electrical iodoform synthesis is a typical secondary process. 

The aminocyclitol moiety was synthesized in a stereocontrolled manner from cis-2-butene-l,4-diol (Scheme 40)112 by conversion into epoxide 321 via Sharpless asymmetric epoxidation in 88% yield.111 Oxidation of 321 with IBX, followed by a Wittig reaction with methyl-triphenylphosphonium bromide and KHMDS, produced alkene 322. Dihydroxylation of the double bond of 322 with OSO4 gave the diol 323, which underwent protection of the primary hydroxyl group as the TBDMS ether to furnish 324. The secondary alcohol of 324 was oxidized with Dess-Martin periodinane to... 

Another C-O bond roactioa of Alcohols is their conversion into alkyl halides (Section 10.7). Tertiary alcohols arc readily converted into alkyl halides by treatiBom with either KCl or HBr otO C. Primary and secondary alcohols are much more rvsistanl to acid, however, and arc hrat converted into lioUdea by tikfauueni with either SOCl o> PDvj. 

Oxidation of Secondary Alcohols.—In the secondary alcohol group (—CHOH—) there is only one hydrogen in addition to the hydroxyl group so that on its conversion into hydroxyl and the subsequent loss of water there is left no hydrogen united to this carbon, and we obtain... 

Dehydration of secondary alcohols. Hutchins et a .1 attempted to convert irans-4-tm-butylcyclohexanol into the corresponding civ-iodide by treatment with MTPI in HMPT at room temperature. Instead, they obtained 4-ieri-butylcyclohexene in 88 % yield. They then found that secondary alcohols in general are dehydrated by treatment with a twofold excess of MTPI in HMPT at 25-75° for 0.25-25 hr. Primary alcohols are converted into the corresponding iodide in excellent yield under these conditions tertiary alcohols are practically inert. Dehydration apparently involves initial conversion into the corresponding inverted iodide followed by dehydrohalogenation induced... 

Olefin synthesis from alcohols. Primary and secondary alcohols containing a /3-hydrogen can be converted into olefins by conversion into the alkoxide (sodium hydride, DMF) and then reaction of the alkoxide with N,N-dimethylthiocarbamoyl chloride to form an O-alkyl dimethylthiocarbamate. These derivatives on heating to 180-200° for 2 hours decompose to form olefins. The other product is dimethylammonium dimethylthiocarbamate (2). The complete sequence is formulated as follows ... 

Since nitriles are usually conveniently accessible their conversion into carboxylic acids is important for aliphatic, aromatic hydrocarbon and heterocyclic chemistry. Hydrolysis of the nitrile group requires energetic conditions, such as treatment with strong acid or alkali. The individual case will decide whether acid or alkali is used. Where possible, acid hydrolysis is preferable, especially by concentrated hydrochloric acid, and, to increase the solubility of the nitrile, this is often carried out in presence of acetic acid. For the same reason alkaline hydrolysis is effected in presence of alcohol or pyridine, sometimes under pressure. Primary cyanides are hydrolysed more easily than secondary or tertiary ones, and aliphatic more easily than aromatic. The last traces of the nitrile and of the amide formed as intermediate are not always easy to remove. In some cases hydrolysis is stopped at the amide stage and completed by a different process, e.g., by means of nitrous acid (see page 345).621... 

Vedejs and Chen [39] described an efficient non-enzymatic system able to approach the efficiency of some of the lipase methods in enantioselectivity. The reaction was carried out in a 2 1 ratio racemic secondary alcohol acylating agent, in contrast to Evans procedure. The pyridinium salt 8 was prepared by reaction of the chiral 4-dimethylaminopyridine (DMAP) 6 with the commercially available chloroformate 7. This pyridinium salt proved to be unreactive to secondary alcohols. The reactivity was found only upon strict experimental conditions addition of a Lewis acid, then the racemic alcohol, followed by addition of a tertiary amine gave the carbonate 9. Under these conditions (using MgBr2 and triethylamine), (2-naphthyl)- -ethanol was converted (room temperature, 20 h and 54% conversion) into the (S)-carbonate (82% ee). The recovered alcohol showed 83% ee, revealing a stereoselectivity s=39 for the process. A number of 1-arylalkanols have been resolved by this procedure in 20-44% yield (based on the racemic material) and 80-94% ee. For the use of this system in enantiodivergent reactions, see Schemes 6.1 and 6.32. 

The Mitsunobu reaction, discovered by Mitsunobu in the late 1960s, has become one of the most widely used reactions in organic chemistry. The reaction has become the standard method for the inversion of secondary alcohols, the conversion of alcohols into amines and sulfides, and many other applications. New uses for this versatile reaction continue to be developed. The Mitsunobu reaction, due to its mild reaction conditions, has found wide application in total synthesis, and heterocyclic and medicinal chemistry. Since the Mitsunobu reaction has been extensively reviewed during the last thirty years, this chapter will focus primarily on applications of the Mitsunobu reaction during the last fifteen years. This review will cover recent examples for the various uses of the Mitsunobu reaction and introduce several new applications of the reaction. Recently developed phosphine and azadicarboxylate reagents will be covered as well. 

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