Stereoselectivity in Alcohol Dehydration

In addition to being regioselective, alcohol dehydrations are stereoselective. A stereoselective reaction is one in which a single starting material can yield two or more stereoisomeric products, but gives one of them in greater amounts than any other. 

Alcohol dehydrations tend to produce the more stable stereoisomer of an aUcene. Dehydration of 3-pentanol, for example, yields a mixture of trans-2-pentene and cw-2-pen-tene in which the more stable trans stereoisomer predominates. 

The biological dehydrogenation of succinic acid described in Section 5.8 is 100% stereoselective. Only fumaric acid, which has a trans double bond, is formed. High levels of stereoselectivity are characteristic of enzyme-catalyzed reactions. 

In addition to being regioselective, alcohol dehydrations are stereoselective. A stereoselective reaction is one in which a single starting material can yield two or more ster-eoisomeric products, but gives one of them in greater amounts than any other. Alcohol dehydrations tend to produce the more stable stereoisomer of an alkene. Dehydration of 3-pentanol, for example, yields a mixture of ran5-2-pentene and c/5-2-pentene in which the more stable trans stereoisomer predominates. 

What three alkenes are formed in the acid-catalyzed dehydration of 2-pentanol  

Step 3 in Mechanism 5.1 shows water as the base that abstracts a proton from the carbocation. Other Brpnsted bases present in the reaction mixture that can function in the same way include ferf-butyl alcohol and hydrogen sulfate ion. 

---

Compound (80), prepared from 2-methylcyclopentane-l,3-dione and methyl 2-chloroacrylate followed by the sequence (76)-> (77)-> (78)- (79) (resolved)— (80), combined with (71) (prepared from m-methoxyphenylstyrene and diborane) to form the seco-steroid (82)/ Acetic anhydride-toluene-p-sulphonic acid then cyclized this stereoselectively to furnish the triacetate (83) which on saponification gave the triol (84). Interestingly, this compound reacted with toluene-p-sulphonic acid in alcohol to produce, by dehydration and change of configuration at C-14, the compound (85), which served as a source of various 8a-oestrone compounds. Compound (84) on treatment with boron trifluoride etherate underwent pinacol transformation in preference to dehydration to yield the ketone (86) this ketone was correlated with the known compound (87). 

The second stereochemical aspect of alkene hydrogenation concerns its stereoselectivity. A stereoselective reaction is one in which a single starting material can give two or more stereoisomeric products but yields one of them in greater amounts than the other (or even to the exclusion of the other). Recall from Section 5.11 that the acid-catalyzed dehydration of alcohols is stereoselective in that it favors the formation of the more stable stereochemistry of the alkene double bond. In catalytic hydrogenation, stereoselectivity... 

A 1,2,3-triazole-promoted iron(III)-catalysed propargyl alcohol dehydration has been developed for the synthesis of conjugated enynes (Scheme 3) The products were obtained in good to excellent yields (up to 95%) with a large substrate scope and excellent Z stereoselectivity. Addition of readily available 1,2,3-triazole to FeCl3 provided a practical and efficient catalyst system, which gave the critical chemoselectivity for the carbon-oxygen bond activation. 

Hydrogenation of alkynes to alkenes using the Lindlai catalyst is attractive because it sidesteps the regioselectivity and stereoselectivity issues that accompany the dehydration of alcohols and dehydrohalogenation of alkyl halides. In tenns of regioselectivity, the position of the double bond is never in doubt—it appears in the carbon chain at exactly the sane place where the triple bond was. In tenns of stereoselectivity, only the cis alkene forms. Recall that dehydration and dehydrohalogenation normally give a cis-trans mixture in which the cis isomer is the minor product. 

In addition to the synthetic applications related to the stereoselective or stereospecific syntheses of various systems, especially natural products, described in the previous subsection, a number of general synthetic uses of the reversible [2,3]-sigmatropic rearrangement of allylic sulfoxides are presented below. Several investigators110-113 have employed the allylic sulfenate-to-sulfoxide equilibrium in combination with the syn elimination of the latter as a method for the synthesis of conjugated dienes. For example, Reich and coworkers110,111 have reported a detailed study on the conversion of allylic alcohols to 1,3-dienes by sequential sulfenate sulfoxide rearrangement and syn elimination of the sulfoxide. This method of mild and efficient 1,4-dehydration of allylic alcohols has also been shown to proceed with overall cis stereochemistry in cyclic systems, as illustrated by equation 25. The reaction of trans-46 proceeds almost instantaneously at room temperature, while that of the cis-alcohol is much slower. This method has been subsequently applied for the synthesis of several natural products, such as the stereoselective transformation of the allylic alcohol 48 into the sex pheromone of the Red Bollworm Moth (49)112 and the conversion of isocodeine (50) into 6-demethoxythebaine (51)113. 

The steric effects may be more pronounced in heterogeneous catalysts than in homogeneous reactions in solution. The rigid, solid surface restricts the approach of the reactants to the active centers and interaction between the reactants. The steric requirements are quite stringent when a two-point adsorption is necessary and when, in consequence, the internal motion of the adsorbed molecules is limited. In this way, the stereoselectivity of some heterogeneous catalytic reactions, for example, the hydrogenation of alkenes on metals (5) or the dehydration of alcohols on alumina and thoria (9), have been explained. 

In preparation for the eventual removal of the undesired oxygen function at C-10 of 313 via a Birch reduction, the phenol 313 was phosphorylated with diethyl phosphorochloridate in the presence of triethylamine to give 314, which underwent stereoselective reduction with sodium borohydride with concomitant N-deacylation to deliver the amino alcohol 315. N-Methylation of 315 by the Eschweiler-Clarke protocol using formaldehyde and formic acid followed by ammonolysis of the ester group and acetylation of the C-2 hydroxyl function afforded 316. Dehydration of the amide moiety in 316 with phosphorus oxychloride and subsequent reaction of the resulting amino nitrile 317 with LiAlH4 furnished 318, which underwent reduction with sodium in liquid ammonia to provide unnatural (+)-galanthamine. 

Dehydration. Although early studies of dehydration of tertiary alcohols were shown to involve an anti-elimination, little use of this stereoselectivity has been applied to preparation of (E)- or (Z)-alkenes. This reaction is useful for preparation of (E)- and (Z)- A22- or A23-sterols, and in combination with svn-hydroboration of alkenes for isomerization of trisubstituted steroidal alkenes.1... 

The ring-A/B moiety (286) of the naturally occurring C2g steroidal lactone withaferin A has been incorporated into cholestane as outlined in Scheme 14.156 Hydride reduction of the epoxide (280) gave the diol (281) which reacted stereo-specifically with peroxy-acid to yield the a-epoxide (282), and this was in turn converted into the epoxy-enone (283). The yield of (283) based upon the epoxy-dienone (261) is 70%. Ring-opening of the oxide (283) afforded the 5a-alcohol (284) which was dehydrated to the A2,5-diene (285). The A5-bond was then epox-idized stereoselectively and quantitatively to the 5/3-oxide (286). Ring A of this 5/3 -oxide was shown to be in the boat conformation. 

For the structural optimization of the tricyclic triazolium salt 119 the cw-tricyclic lactam 126 was chosen as the precursor for the synthesis of the tetracyclic triazolium salt 127. The diastereo- and enantiopure y-lactam 126 was synthesized following a procedure reported by Ennis et al. (Scheme 32) (Ennis et al. 1996 Nieman and Ennis 2000). a-Tetralone (124) was a-alkylated with ethyl bromoacetate and subsequently hydrolyzed to the corresponding carboxylic acid. Condensation with (R)-phenylglycinol yielded the lactam 125 as a single stereoisomer. Stereoselective reduction, dehydration of the alcohol, and acid-catalyzed enamine hydrolysis provided the cis-tricyclic lactam 126. The one-pot procedure that had previously been successful in the synthe-... 

---