Pinacol rearrangement with Lewis acids

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

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... 

Pinacol rearrangement driven by the release of the ring strain of a cyclobutane ring has been employed in an extremely efficient manner to form cyclopentanone derivatives. Experimentally. the Lewis acid mediated aldol condensation of benzaldehyde with l,2-bis(trimethyl-siloxy)cyclobutcne at —78 C gave the pinacol 1 in its silylated form.35,36 Subsequent treatment of this pinacol with trifluoroacetic acid at room temperature afforded 2-phenyl-cyclopentane-l,3-dione (2) in 97% yield.35,36... 

The most general method for the synthesis of tetrahydrofurans based upon the IMSC methodology was developed by Overman et al. [53, 54, 94—96] For example, condensation of alcohol 221 with an aldehyde or a ketone in the presence of a Lewis acid leads to the formation of the carbocations 222a,b. The tertiary carboca-tion 222a undergoes a pinacol rearrangement and forms the desired heterocycle 224 (Scheme 13.82). Overman et al. used this approach during the synthesis of the various cladiellin diterpenes, which possess the core skeleton 224 [53]. 

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. 

An interesting double ring expansion sequence developed by Vogel involves the initial pinacol coupling of cyclobutanone, isomerization to ketone 79 in acid, followed by reduction and Lewis acid-promoted Wagner-Meerwein rearrangement with dehydration (Scheme 19).129) For preparative purposes, 80 can be more... 

Oxaziridines are converted to ring-expanded lactams under photochemical conditions. A-Tosyl aziridines with an a-hydroxyalkyl substituent give a pinacol rearrangement product in the presence of Lewis acids, such as Sml2> in this case a keto-A-tosyl amide. ... 

A similar stereoselectivity has been described for the Lewis acid catalyzed pinacol rearrangement of vinyl-24 and cyclopropyl-substituLed25 hydroxysulfonates 16 (via mesylation) and 17. Of note is a dramatic rate enhancement observed for the [1,2] rearrangement of silyl-substituted substrates 16, an observation consistent with the well-documented ability of silicon substituents to stabilize / -carbocations. 

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. 

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. 

When aromatic pinacols are reacted with an acid, products often arise from dehydration and rearrangement.5 This general conversion is known as the pinacol rearrangement. The pinacol rearrangement may be promoted by both Brdnsted and Lewis acids.6 In the procedure described here, superacidic triflic acid is reacted with an aryl pinacol and a dehydrative cyclization occurs to give the substituted phenanthrene product. Related to this conversion, the chemistry of benzopinacol in sulfuric acid and triflic acid is contrasted in Scheme 1. We have proposed that the superacidic triflic acid causes the formation of diprotonated intermediates which promote the dehydrative cyclization.4... 

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