Asymmetric 1,2-rearrangements

Overman LE, Owen CE, Pavan MM, Richards CJ (2003) Catalytic asymmetric rearrangement of allylic N-aryl trifluoroacetimidates. A useful method for transforming prochiral allylic alcohols to chiral allylic amines. Org Lett 5 1809-1812... 

Anderson CE, Overman LE (2003) Catalytic asymmetric rearrangement of allylic trichlor-oacetimidates. A practical method for preparing allylic amines and congeners of high enantiomeric purity. J Am Chem Soc 125 12412-12413... 

Prasad RS, Anderson CE, Richards CJ, Overman LE (2005) Synthesis of tert-leucine-derived cobalt oxazoline palladacycles. Reversal of palladation diastereoselectivlty and application to the asymmetric rearrangement of N-aryl trifluoroacetimidates. Organometallics 24 77-81... 

B. Enantioselective Access to Allylic Alcohols via Asymmetric Rearrangement... 

TABLE 2. Stoichiometric asymmetric rearrangement of cyclohexene oxide using HCLA 54 to 59... 

The first example of such a process was reported in 1994 by Asami, who noticed that LDA was less reactive than HCLA 53 toward oxirane and thus proposed its use as a co-base in a catalytic cycle . Based upon this seminal result, the system has been extended to other HCLAs and various co-bases have been tested Selected results for the asymmetric rearrangement of cyclohexene oxide mediated by sub-stoichiometric quantities of HCLA are collected in Table 4. 

TABLE 5. Catalytic asymmetric rearrangement of oxiranes mediated by HCLA 56a and 56b... 

TABLE 8. Asymmetric rearrangement of various oxiranes using base 74... 

Asymmetric Rearrangment and Kinetic Resolution of Allylic Sulfinates... 

Chiral 2,2-disubstituted cyclobutanones have been obtained by asymmetric rearrangement of chiral sulfinyl- 177,178 and sulfanylcyclopropanes.179 Using readily available cyclopropyl 4-tolyl (/ )-sulfoxide (l),180 the requisite sulfinylcyclopropanes 3 and 3 were obtained by a sequence of lithiation, reaction with carboxylic acid esters and stereoselective addition of Grignard reagents to the ketones 2 thus formed.178 The corresponding sulfanylcyclopropanes 4 and 4 resulted from a sequence of protection, reduction and deprotection.179... 

The asymmetric rearrangement of peroxy radical (5) has recently been used as the key step in the asymmetric synthesis of Plakorin (Scheme l).17 The thermal isomerization of buta-1,2- to buta-1,3-diene has been studied using ab initio calculations and the mechanism concluded to proceed stepwise via radical intermediates.18 The competition between cyclopropyl formation and the homoallyl-homoallyl radical rearrangement has been studied in the radical (6) and found to give the 3-exo cyclization product (7) and the rearranged product (8) in a 1 5 ratio, respectively, under the conditions shown (Scheme 2).19... 

The catalytic asymmetric rearrangement of functionalized cyclohexene and cyclopentene oxides to give chiral allylic alcohols has been studied using sub-stoichiometric amounts of a chiral lithium amide in combination with a stoichiometric amount of different lithiated imidazoles (Scheme 47).79... 

The groups of Ahlberg and Davidsson have reported the formation of mixed complexes between Li-5 and lithiomethylimidazole (LiMIM), Li-5/LiMIM, used in catalytic asymmetric rearrangement of cyclohexene oxide68. 

Asymmetric rearrangement of cyclohexene oxide. Cyclohexene oxide is rearranged to (S)-2-cyclohexene-l-ol in 92% ee by the chiral lithium amide (2) prepared from n-butyllithium and 1. Several related (S)-2-(disubstituted aminomethyOpyrrolidines prepared from (S)-proline are almost as stereoselective. ... 

As with many catalytic systems, additives can play an important role. During optimization of the asymmetric rearrangement of cyclopentenyl tertiary ethers to chiral cyclohexenyl tertiary ethers, Hoveyda found a strong solvent effect on the enantioselectivity of the reaction using (97b). Lewis basic (see Lewis Acids Bases) additives were used to modify the catalyst since (97i) is Lewis acidic and coordination could change the equilibration of the Mo-alkyhdene isomers and, thus, could alter the enantioselectivity. Coordination of Lewis base to the metal center might also change the fit of the chiral pocket. Addition of 10 equiv (vs. substrate) of THF substantially increased the enantiomeric excess of the product in the model transformation (Table 10). ft was surmised that... 

The use of Al(III) complexes as catalysts in Lewis acid mediated reactions has been known for years. However, recent years have witnessed interesting developments in this area with the use of ingeiuously designed neutral tri-coordinate Al(lll) chelates. Representative examples involving such chelates as catalysts include (1) asymmetric acyl halide-aldehyde cyclocondensations, " (2) asymmetric Meerwein-Schmidt-Ponndorf-Verley reduction of prochiral ketones, (3) aldol transfer reactions and (4) asymmetric rearrangement of a-amino aldehydes to access optically active a-hydroxy ketones. It is important to point out that, in most cases, the use of a chelating ligand appears critical for effective catalytic activity and enantioselectivity. 

Anderson, C. E., Overman, L. E. Catalytic Asymmetric Rearrangement of Allylic Trichloroacetimidates. A Practical Method for Preparing Allylic Amines and Congeners of High Enantiomeric Purity. J. Am. Chem. Soc. 2003, 125, 12412-12413. 

Asymmetric rearrangement of alkenyl alk)myl carhinols with a chiral Rh-BINAP catalyst furnishes 3-alkynyl ketones. The transformation is synthetically equivalent to... 

Isomerization of allylic alcohols occurs in reasonable yields but with poor enantioselectivity [22], although kinetic resolution of 4-hydroxycyclopentenone has been reported [23]. Reliable laboratory-scale procedures for the synthesis of BINAP and for the asymmetric rearrangement have been published [24,25], making this a good candidate for further applications in asymmetric synthesis. 

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