Olefination tertiary alcohols

From the initial studies, the following trend of reactivity was observed generally in order of decreasing activity monohydric alcohols > olefins > tertiary alcohols... 

Tertiary alcohols are more readily dehydrated than secondary alcohols, whilst primary alcohols are dehydrated with comparative difficulty. Thus the reaction proceeds easily with 33 per cent, sulphuric acid (1 acid 2 water, by volume) for amyl alcohol, but 50 per cent, (by volume) is required for aec.-amyl alcohol. Higher concentrations of acid tend to lead to increasing polymerisation of the olefine and are therefore usually avoided. 

Olefins add anhydrous acetic acid to give esters, usually of secondary or tertiary alcohols propjiene [115-07-1] yields isopropyl acetate [108-21-4], isobutjiene [115-11-7] gives tert-huty acetate [540-88-5]. Minute amounts of water inhibit the reaction. Unsaturated esters can be prepared by a combined oxidative esterification over a platinum group metal catalyst. Eor example, ethylene-air-acetic acid passed over a palladium—Hthium acetate catalyst yields vinyl acetate. 

Alkyl boric acid esters derived from straight-chain alcohols and aryl boric acid esters are stable to relatively high temperatures. Methyl borate is stable to 470°C (11). Trialkoxyboranes from branched-chain alcohols are much less stable, and boranes from tertiary alcohols can even decompose at 100°C (12). Decomposition of branched-chain esters leads to mixtures of olefins, alcohols, and other derivatives. 

Almost 40 years later the Lummus Co. patented an integrated process involving the addition of chlorine along with the sodium chloride and sodium hydroxide from the cathode side of an electrolytic cell to a tertiary alcohol such as tertiary butanol to produce the tertiary alkyl hypochlorite. The hypochlorite phase separates, and the aqueous brine solution is returned to the electrolytic cells. The alkyl hypochlorite reacts with an olefin in the presence of water to produce a chlorohydrin and the tertiary alcohol, which is returned to the chlorinator. With propylene, a selectivity to the chlorohydrin of better than 96% is reported (52). A series of other patents covering this technology appeared during the 1980s (53—56). 

The reaction gives poor yields of ethers with secondary and tertiary alcohols dehydration to form the corresponding olefin is a more favorable reaction. The reaction fails for the production of diaryl ethers from phenols. 

Highly fluorinated tertiary alcohols usually give olefins on iluormation with sulfur tetrafluoride [759/, but in certain cases, replacement of the hydroxyl group with fluorine occurs under mild conditions Hexafluoro-2-arylpropan-2-ols react with sulfur tetrafluoride at low temperatures to give high yields of heptafluoro-isopropylarenes [766] (equation 77), and similarly, 3,8 dihydroxy 9,9,9,10,10,10-hexafluoro-p-menthane affords 3,8,9,9,9,10,10,10-octafluoromenthane [766] (equation 78)... 

The AE reaction has been applied to a large number of diverse allylic alcohols. Illustration of the synthetic utility of substrates with a primary alcohol is presented by substitution pattern on the olefin and will follow the format used in previous reviews by Sharpless but with more current examples. Epoxidation of substrates bearing a chiral secondary alcohol is presented in the context of a kinetic resolution or a match versus mismatch with the chiral ligand. Epoxidation of substrates bearing a tertiary alcohol is not presented, as this class of substrate reacts extremely slowly. 

The above procedure describes the only known preparation of the inner salt of methyl (carboxysulfamoyl)triethylammonium hydroxide and illustrates the use of this reagent to convert a primary alcohol to the corresponding urethane.2 Hydrolysis of the urethane would then provide the primary amine. The method is limited to primary alcohols secondary and tertiary alcohols are dehydrated to olefins under these conditions, often in synthetically useful yields.2... 

Taft s Terminal olefins, synthesis of 629 Tertiary alcohols, allylic, epimerization of 736... 

In 2009, Tu et al. developed a novel iron-catalyzed C(sp )-C(sp ) bond-forming reaction between alcohols and olefins or tertiary alcohols through direct C(sp )-H functionalization. A series of primary alcohols were treated with alkenes or tertiary alcohols as their precursors, using the general catalysis system FeCls (0.15 equiv)/ 1,2-dichloroethane (DCE) (Scheme 36) [46]. 

By 1990, most of the catalytic reactions of TS-1 had been discovered. The wide scope of these reactions is shown in Fig. 6.1.35 Conversions include olefins and diolefins to epoxides,6,7 12 16 19 21 24 34 36 38 13 aromatic compounds to phenols,7,9 19 25 27 36 ketones to oximes,11 20 34 46 primary alcohols to aldehydes and then to acids, secondary alcohols to ketones,34-36 42 47-30 and alkanes to secondary and tertiary alcohols and ketones.6 34 43 31 52... 

The isopropenyl side chain may derive by elimination of a tertiary alcohol or ether as in 202. Such a masking of the olefin avoids a possible competing vinylcyclopropane rearrangement. The correspondence of the cyclopentene of 202 with the vinylcyclopropane in 203 now becomes obvious. The presence of the dimethylcarbinol side chain now also offers the opportunity for its introduction by addition of a cyclopropyl anion to acetone. The feasibility of creating such an anion by fluoride initiated desilylation... 

Photocycloaddition of allene to cyclohexenone (341) gave the (3,y-enone (342), which reacted with vinyl magnesium bromide to produce the tertiary alcohol (343) in 79% yield. When the compound (343) was treated with KH and 18-crown-6 in THF at room temperature for two hours and quenched with aq. NH4C1, the cyclobutene (344) was obtained. The thermal ring opening of the cyclobutene (344) proceeded in toluene in a sealed-tube at 180 °C for twelve hours to give a readily separable 5 1 mixture of the civ-olefin (345), and the trans-olefin (346) respectively in 95 % yield. Moreover, (345) could be converted to a mixture of (346) and (345) in the ratio of 10 1 by irradiation. The compounds (345) and (346) possess the skeleton of the germacranes (347), (348) and (349) 122). 

Along with catalytic asymmetric epoxidation, the related dihydroxylation of olefins is another venerable catalytic enantioselective process that is widely used by the modern organic chemist. An application of this important transformation may be found in Corey s 1994 preparation of optically pure 109 (Scheme 16), an intermediate in Corey s 1985 total synthesis of ovalicin.1181 The catalytic asymmetric dihydroxylation that affords 108 solves one of the most challenging problems in the total synthesis installment of the tertiary alcohol center with the appropriate relative and absolute stereochemistry. 

The rate of hydration of an olefin increases with acidity. It has recently been demonstrated that the hydration of isobutylene follows the Ho acidity function, i.e. dlogkj — dHo) = 1, where Hq is the acidity function defined by equation (10). The behaviour of secondary and tertiary alcohols in 0-55 % H2SO4 is very similar (Beishlin, 1963). 

Halogen-lithium exchange of iodide 71 and subsequent addition of 2-acetyl-furan (72) to the resultant organolithium intermediate yielded two diastereomeric tertiary alcohols (dr=l l), which were converted to (E)-olefin 73 with complete diastereoselectivity upon brief exposure to catalytic amounts of concentrated aqueous hydrogen chloride (Scheme 11) [18]. Diastereoselective hydroboration/oxidation of 73 gave largely the desired stereoisomer 74 due to... 

The dehydration of alcohols is mostly an acid-catalyzed reaction and much work has been done by Taft and co-workers to elucidate the mechanism (7 5-7 7). These investigators proved that the intermediate in the dehydration of tertiary alcohols or hydration of branched olefins in dilute acid solutions resembles the conjugate acid of the olefin and it is... 

Dehydrates secondary and tertiary alcohols to give olefins, but forms ethers with primary alcohols. Cf. Burgess dehydrating reagent. 

In the case of secondary and tertiary alcohols the strong acid HRu(C0) I causes a very rapid dehydration of the substrates to olefins which have been found in very large amount in the reaction mixtures together with their oligomerization products. 

Essentially the same route is followed for the synthesis of the triphenylethylene nitromifene (8-5). The sequence starts with Friedel-Crafts acylation of the alkylation product (8-1) from phenol and 1,2-dibromoethane with the acid chloride from anisic acid (8-2). The displacement of bromine in the product (8-3) with pyrrolidine leads to the formation of the basic ether and thus (8-4). Condensation of that product with benzylmagnesium bromide gives the tertiary alcohol (8-5). This product is then treated with a mixture of nitric and acetic acids. The dehydration products from the first step almost certainly consist of a mixture of the E and Z isomers for the same reasons advanced above. The olefin undergoes nitration under reaction conditions to lead to nitromifene (8-6) as a mixture of isomers [8] the separated compounds are reported to show surprisingly equivalent agonist/antagonist activities. 

Isocyanates readily react with primary alcohols at 25°-50°C, whereas secondary alcohols react 0.3 as fast, and tertiary alcohols approximately 0.005 as fast as the primary [2]. Thus, the effect of steric hindrance shows a pronounced effect on these reactions. For example, triphenylcarbinol has been reported to be completely unreactive [3a, b]. Other tertiary alcohols such as f-butanol may react under uncatalyzed conditions with isocyanates to give olefin formation, as shown in Eq. (4), using phenyl isocyanate [4, 5]. 

The olefins formed under these conditions using other tertiary alcohols tend to follow the Hofmann rule [6a]. However, tertiary alcohols and phenols [6b] can be made to react with isocyanates to give urethanes when they are catalyzed by acids or bases such as pyridine [6b], triethylamine, sodium acetate, boron trifluoride etherate, hydrogen chloride, or aluminum chloride [7]. Table I indicates the results of preparing phenylurethanes of tertiary alcohols... 

A major limitation on the production of alcohols by olefin hydration is the fact that the products consist almost solely of secondary or tertiary alcohols (excepting, of course, ethyl alcohol). The normal or primary alcohols are made by other means (but also from petroleum hydrocarbons). It appears more difficult to prepare C5 and higher alcohols by the hydration of olefins since they are produced commercially by other means. One of the problems encountered (81) is excessive polymerization of the higher olefins when contacted with aqueous sulfuric acid. 

The addition, therefore, follows Markovnikov s rule. Primary alcohols give better results than secondary, and tertiary alcohols are very inactive. This is a convenient method for the preparation of tertiary ethers by the use of a suitable olefin such as Me2C=CH2. 

Carboxylic esters are produced by the addition of carboxylic acids to olefins, a reaction that is usually acid-catalyzed (by proton or Lewis acids182) and similar in mechanism to 5-4. Since Markovnikov s rule is followed, hard-to-get esters of tertiary alcohols can be prepared from olefins of the form R2C=CHR.183 When a carboxylic acid that contains a double bond in the chain is treated with a strong acid, the addition occurs internally and the product is a y- and/or a 8-lactone, regardless of the original position of the double bond in the chain, since strong acids catalyze double bond shifts (2-2).184 The double bond always migrates to a position favorable for the reaction, whether this has to be toward or away from the carboxyl group. Carboxylic esters have also been prepared by the acyloxymercuration-demercuration of olefins (similar to the procedures mentioned in 5-2 and 5-4).185... 

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