Epoxides homoallylic amines

Aza-Prins Cyclization of Epoxides with Homoallylic Amines. 234... 

Cross-cyclization of epoxides with homoallylic amines is an easy way to access tetrahydropyran moieties, which form the core structure of many biologically important natural products such as avermectins, aplysiatoxin, oscillatoxins, latrunculins, talaromycins, acutiphycins, and apicularens. Even though many methods are available for the synthesis of this moiety [14—24], its importance and wide applicability demands further methods. 

Stereoselective synthesis of trans 4-chloro-2-substituted piperidines can be achieved by the reaction of epoxides and N-protected homoallyllic amines using BiCl3 as the Lewis acid catalyst (Fig. 3). This method furnishes very good generality with respect to various epoxides with a regioselectivity that favors the trans-... 

Fig. 3 Aza-Prins cyclization of epoxides with N-protected homoallylic amines...

Diamides of tartaric acid with primary amines have been used as chiral ligands for titanium-and zirconium-catalyzed epoxidations of homoallylic alcohols by the Sharpless method (Section D.4.5.2.4.). Such diamides are conveniently obtained from dimethyl or diethyl tartrate by reaction with the corresponding amine38. The iV,A A, /V -tetrarnethyl diamide has been used for the formation of chiral dioxolanes (Section D.1.5.1.) and in the synthesis of chiral alkenes (Section D.l.6.1.5.). 

Although the homoallylic- cyclopropylcarbinyl cyclization is well-precedented in carbonium ion chemistry (101, 102) there seem to be no reports of the direct cyclization of the tertiary 4-terpinenyl carbonium ion. However, deamination of cyclohex-3-enyl amine and solvolysis cyclo-hex-3-enyl tosylate gives exo- and n /o-bicyclo[3.1.0]hex-2-yl derivatives as 6—43% of the products resulting from nucleophilic capture (101, 103, 104). The modest yield of bicyclic products in these reactions apparently is the result of competing nucleophilic capture prior to cyclization and hydride shift to the 2-cyclohexenyl cation. More efficient cyclization occurs in the acetolysis of 2-bicyclo[2.2.2]oct-5-enyl tosylate (49) owing to the rigid boat-like conformation of the precursor (105). The high efficiency of the base-catalyzed cyclization of the epoxide of 4-iso-... 

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