Epoxides pinacol rearrangement

Based on the labeling experiments, a plausible mechanism involving mthenium vinylidene intermediates SS is proposed in Scheme 6.21. Cydization of this vinylidene intermediate leads to the formation of the epoxy carbenium 56, which then undergoes an epoxide opening to form l,4-dien-3-ol 57. A subsequent pinacol rearrangement of this alcohol furnishes ketone 58, providing the required skeleton for the observed phenol product 54. 

Hydride Reduction of a Carbonyl Group 454 Reaction of a Tertiary Alcohol with HBr(S[ 1) 480 Reaction of a Primary Alcohol with HBr (SN2) 480 Reaction of Alcohols with PBr3 485 (Review) Acid-Catalyzed Dehydration of an Alcohol 487 The Pinacol Rearrangement 495 Cleavage of an Ether by HBr or HI 639 Acid-Catalyzed Opening of Epoxides in Water 649 Acid-Catalyzed Opening of an Epoxide in an Alcohol Solution 650... 

The intermediate cation in a pinacol rearrangement can equally well be formed from an epoxide, and treating epoxides with acid, including Lewis acids such as MgBr2, promotes the same type of reaction. 

A good way to prepare p-diketones consists of heating a,p-epoxy ketones at 80-140°C in toluene with small amounts of (Ph3P)4Pd and l,2-bis(diphenyl-phosphino)ethane. ° Epoxides are converted to 1,2-diketones with Bi, DMSO, O2, and a catalytic amounts of Cu(OTf)2 at 100°C. a,p-Epoxy ketones are also converted to 1,2-diketones with a ruthenium catalyst or an iron catalyst. Epoxides with an a-hydroxyalkyl substituent give a pinacol rearrangement product in the presence of a ZnBr2 " or Tb(OTf)3 catalyst to give a y-hydroxy ketone. 

Problem 28.9 The following reactions have all been found to yield a mixture of pinacol and pinacolone, and in the same proportions treatment of 3-amino-2,3-dimethyl-2-butanol with nitrous acid treatment of 3-chloro-2,3-dimethyl-2-butanol with aqueous silver ion and acid-catalyzed hydrolysis of the epoxide of 2,3-dimethyl-2-butene. What does this finding indicate about the mechanism of the pinacol rearrangement ... 

Pocker, Y., Ronald, B. P. Kinetics and mechanism of vic-diol dehydration. I. Origin of epoxide intermediates in certain pinacolic rearrangements. J. Am. Chem. Soc. 1970, 92, 3385-3392. 

The important study of Berti et al. (also discussed in the context of the pinacol rearrangement see equations 8 to 11 of Chapter 3.2 in this volume) included BFs-induced reactions of the cis- and transepoxides (85 equation 36) and (91 equation 37), respectively. These very informative reactions show that, at least under the particular reaction conditions used in this work (benzene as solvent), the Coxon mechanism must be expanded to include an appreciable antiperiplanar geometrical feature. Unlike the pinacol rearrangements of the related diols, which gave only ketone (89) and aldehyde (90) under the same conditions, epoxide (85) gives, in addition to these same products, a significant amount of aldehyde (87). This appears to require the involvement of the twist boat conformer (86), which is the expected intermediate if the shown starting material conformer opens at the tertiary benzylic center with antiperiplanar constraints. Subsequent rotation of (86) to the chair conformer (88) allows formation of the ketone (89) and the aldehyde (90). 

The cleaner reactions of the halohydrins show that these, if formed by anti opening and not subsequently epimerized, cannot account for the product mixtures from the epoxides. House proposed a competing carbenium ion route for both epoxides, leading to the normal pinacol rearrangement (carbenium ion) product, the aldehyde (202). 

In a variety of cases of epoxide-alkene cyclizations, undesired side reactions such as pinacol rearrangement to carbonyl compounds, or 1,2-diol formation can occur, precluding the cyclization. Corey and Sodeoka have recommended the use of methylaluminum dichloride (MeAlCl2) as catalyst to alleviate such problems <91TL7005>. Equation (3) illustrates the efficacy of this method in effecting optimal yields of cyclization products. 

From Table 2 (entry 5) and Table 3 (entry 5) it is apparent that the Ti-Al-Beta catalyzed pinacol rearrangement results in a higher yield of pinacolone 4 than the direct rearrangement starting from the epoxide. Consequently, in order to promote the rearrangement of epoxide 2 to pinacolone 4 via pinacol 3, 2 equivalents of water (relative to the amount of epoxide) were added at the start of the reaction (Scheme 4 conditions A). Furthermore, after formation of the diol a Dean-Stark apparatus was used to remove the excess water (conditions B). 

The pinacolic rearrangement of acyclic a-silyloxy epoxides presents an attractive procedure for the stereocontrolled preparation of aldol-type products under extremely mild conditions33 35. Treatment of epoxides with an appropriate Lewis acid catalyst results in a [1,2] shift with net inversion of epoxide stereochemistry to afford highly functionalized /J-hydroxy ketones. 

The products obtained from pinacolic rearrangement of a-silyloxy epoxides can be further transformed in situ by allylsilane addition to the carbonyl group. Lewis acid treatment of 2,3-epoxy-l-phenyl-l-trimethylsilyloxybutane at low temperature followed by addition of 3-trimethylsilylpropene yields 1.3-diol 31 as the only product33. 

It is now known that the pinacol rearrangement is characteristic of all types of 1,2-diol, and that the process is promoted by most electrophilic catalysts. Most of the available data point to the involvement of a carbocationic intermediate, even when the hydroxyl groups are not tertiary. Evidence for a concerted process, i. e. loss of water with the synchronous migration of the substituent, has also been obtained. Other mechanistic possibilities, e. g. transformation through an epoxide or an eno-lic intermediate, can either be ruled out or regarded as playing a role in limited cases only [6]. 

Epoxide rearrangements are closely related to the pinacol rearrangement but allow a more general synthesis of carbonyl compounds. On treatment with acids or Lewis acids, even such weak ones as LiBr or MgBr2, epoxides (26) open to give the more stable carbonium ion (27) which rearranges to a carbonyl compound (28). The order for migration is usually H>Aryl> f-Alkyl > Alkyl > />-Alkyl. 

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