Enantioselective Rearrangements of Epoxides

Dual activation of nucleophile and epoxide has emerged as an important mechanistic principle in asymmetric catalysis [110], and it appears to be particularly important in epoxide ARO reactions. Future work in this area is likely to build on the concept of dual substrate activation in interesting and exciting new ways. 

1 For a review on epoxide hydrolases and related enzymes in the context of organic synthesis, see Faber, K. Biotransformations in Organic Chemistry, Springer New York 2004. 

14 Bartoli, G. Bosco, M. Carlone, A. Loca-telli, M. Massaccesi, M. Melchiorre, P. Sambri, L. Org. Lett. 2004, 6, 

18 For a useful example of nonasymmetric catalytic isocyanosilylation of a meso-epox-ide Imi, K. Yanagihara, N. Utimoto, K.. Org. Chem. 1987, 52, 1013-1016. 

Crotti, P. Di Bussolo, V. Favero, L Mac-chia, F. Pineschi, M. Gazetta Chimica Italiana, 1997, 127, 273-275. 

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Enantioselective rearrangement of epoxides to allylic alcohols 91TA1. Photochemical reactions of glycidyl esters 92MI11. 

Enantioselective deprotonation.2 The rearrangement of epoxides to allylic alcohols by lithium dialkylamides involves removal of the proton syn to the oxygen.3 When a chiral lithium amide is used with cyclohexene oxide, the optical yield of the resulting allylic alcohol is 3-31%, the highest yield being obtained with 1. 

The method involves a highly enantioselective rearrangement of an epoxide and a subsequent Ireland-Claisen rearrangement (see Scheme 31). The enolate Claisen rearrangements of [4-7- /4-4-(l-acyloxy-2,4,6-octatrienyl)]tricarbonyl iron complexes... 

The well-known base-mediated rearrangement of epoxides into allylic alcohols was first reported as an enantioselective process using a chiral base in 1980. Since then, the reaction has received much attention, mostly due to the significance of chiral allylic alcohols in organic synthesis. Major breakthroughs in the area include the use of a substoichiometric amount of chiral base and the development of chiral bases for a true catalytic reaction protocol. Andersson and co-workers have reviewed this area from 1980 to 2001, with emphasis on the period 1997-2001 <2002CSR223>. 

Asami, M., Ishizuka, T. and Inoue, S. (1994) Catal3ftic enantioselective deprotonation of mejo-epoxides by the use of chiral lithium amide. Tetrahedron.Asymmetry, 5, 793-796 Seki, A. and Asami, M. (2002) Catalytic enantioselective rearrangement of mejo-epoxides mediated by chiral lithium amides in the presence of excess cross-linked polymer-bound hthium amides. Tetrahedron, 58, 4655 663. 

Proton removal at the J -epoxide stereocentre is consistently seen in the enan-tioselective a-deprotonation-rearrangement of epoxides using the sparteines this enantioselectivity may be explained by considering a sparteine-RLi-epoxide complex 86, where the C-H bond on the epoxide R stereocentre is held closer to the organolithium than the S stereocentre, minimising non-bonded interactions between sparteine and the epoxide (Scheme 14). 

In a synthesis of (-i-)-asteltoxin, Cha applied the Suzuki-Tsuchihashi rearrangement to silyloxy epoxide 184 for the enantioselective construction of the unusual... 

Rearrangement of an achiral epoxide to give an optically active allyl alcohol, e.g., 1, induced by enantioselective deprotonation with a homochiral base (see p 436 for the determination of absolute configuration)55. 

Cyclopropylidene alcohols have been used in the asymmetric synthesis of 2-hydroxymethylcy-clobutanones via tandem asymmetric epoxidation and enantiospecific rearrangement (Table 5).5 5 The yields and enantiomeric excesses were high. The method was used in the enantioselective syntheses of ( + )- and (—)-a-cuparenone55 and ( + )-laurene.56... 

Tabic 5. Enantioselective Synthesis of 2-Alkyl- and 2-Aryl-2-(hydroxy-methyl)cyclobutanones by Asymmetric Epoxidation and 1,2-Rearrangement of Cyclopropylidene Alcohols55... 

Isomerization of epoxides to allylic alcoholsThis rearrangement has been effected with strong bases and various Lewis acids. Enantioselective rearrangement to optically active allylic alcohols can be effected with catalytic amounts of vitamin B, at 25°. Thus cyclopentene oxide rearranges to (R)-2-cyclopentene-l-ol in 65% ee. The rearrangement of the as-2-butene oxide to (R)-3-butene-2-ol in 26% ee is more typical. 

Lithium amide deprotonation of epoxides is a convenient method for the preparation of allylic alcohols. Since the first deprotonation of an epoxide by a lithium amide performed by Cope and coworkers in 19585, this area has received much attention. The first asymmetric deprotonation was demonstrated by Whitesell and Felman in 19806. They enantioselectively rearranged me.vo-cpoxidcs to allylic alcohols for example, cyclohexene oxide 1 was reacted with chiral bases, e.g. (S,S) 3, in refluxing TFIF to yield optically active (/ )-2-cyclohexenol ((/ )-2) in 36% ee (Scheme 1). 

A number of useful enantioselective syntheses can be performed by attaching a chiral auxihary group to the selenium atom of an appropriate reagent. Examples of such chiral auxiliaries include (49-53). Most of the asymmetric selenium reactions reported to date have involved inter- or intramolecular electrophilic additions to alkenes (i.e. enantioselective variations of processes such as shown in equations (23) and (15), respectively) but others include the desymmefrization of epoxides by ringopening with chiral selenolates, asymmetric selenoxide eliminations to afford chiral allenes or cyclohexenes, and the enantioselective formation of allylic alcohols by [2,3]sigmafropic rearrangement of allylic selenoxides or related species. 

Other Enantioselective Reactions. Enantioselective epoxide elimination by chiral bases has been demonstrated. More recently, the enantioselective [2,3]-Wittig rearrangement of a 13-membered propargylic ally lie ether has been performed using the lithium amide of (f ,f )-(l) as the base for deprotonation (eq 15). For this particular substrate, THF is a better solvent than ether, although pentane produces better results in a related transformation (eq 16). In fact, a change in solvent in this type of reaction has been shown to lead to a reversal of the stereoselectivity of the transformation. ... 

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