Rearrangements pinacol, with epoxides

The limitation of the pinacol is the need for symmetry. This section and the next suggest ways of avoiding this problem. Unsymmetrical epoxides are easily made from alkenes and open with Lewis acid catalysis to give the more substituted of the two possible cations.9 Even such a weak Lewis acid as LiBr opens the epoxide 51 to give the tertiary cation 52 which rearranges by ring contraction to the aldehyde 53. The authors prefer to have the bromocompound 54 as an intermediate.10... 

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... 

Epoxides rearrange with Lewis acids in a pinacol fashion... 

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 ... 

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 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. 

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. 

---