No abstract

Optically active allylic alcohols can be prepared via rearrangement of epoxides using chiral lithium amides, but other than for a small subset of meso-epoxides, insufficient reactivity and enantioselectivity hamper the existing methods. Furthermore, the chiral reagents are often required in large excess. This study presents a general and highly enantioselective process that, in addition, is based on catalytic amounts (5 mol %) of enantiopure (1S,3R,4R)-3-(1-pyrrolidinyl)methyl-2-azabicyclo[2.2.1]heptane and lithium diisopropylamide as the stoichiometric base. The influence of structural modification of the catalyst is studied in terms of activity, enantioselectivity, and aggregation behavior. The utility of the process is demonstrated by its application to a variety of epoxide derivatives (g94% ee for 11 out of 14 examples), including the formal syntheses of, e.g., a prostaglandin core unit, epibatidine, carbovir, faranal, and lasiol. The system is readily extended to the resolution of racemic epoxides, which allows access to highly enantioenriched epoxides or allylic alcohols, even at conversions near 50%.

The base-mediated rearrangement of epoxides into allylic alcohols is a well-known synthetic transformation. The first enantioselective version of the reaction using a chiral base was reported in 1980. Since then, the reaction has received a lot of attention mostly due to the great usefulness of chiral allylic alcohols in organic synthesis. Major breakthroughs in the area were the first report on using a sub-stoichiometric amount of chiral base, and the development of chiral bases for a true catalytic reaction protocol. The present review covers the time from when the first asymmetric epoxide isomerisation reaction was reported (1980) up to now, focusing on the period 1997-2001.

Optically active (1S,3R,4R)-3-[N-(trans-2,5-dialkyl)pyrrolidinyl]methyl-2-azabicyclo-[2.2.1]heptanes were evaluated as catalysts for the enantioselective beta-elimination of meso-epoxides. The (2R,5R)-dimethylpyrrolidinyl-substituted catalyst 4 exhibited exceptionally high enantioselectivity and reactivity, and several substrates were rearranged with enantioselectivities of 98-99% ee. In addition, the use of 4 allowed the first successful, true catalytic rearrangement of the difficult substrates cyclopentene oxide (81%, 96% ee) and (Z)-4-octene oxide (80%, 91% ee).

The chiral ligands 1-phenyl-2-[(4S)-phenyl-4,5-dihydrooxazol-2-yl]propen-2-ol (1a) and [1-phenyl-2-((4S)-phenyl-4,5-dihydrooxazol-2-yl)vinyl]-p-tolylamine (2a) were prepared, together with some structural analogues (1b−e, 2b) in two steps from optically pure phenylglycinol or phenylalaninol. Transition-metal−ligand complexes were isolated from the ligand 1a and Cu(II), Pd(II), and Co(II). The copper complexes of 1a and 2a were found to be highly active catalysts for the asymmetric aziridination of styrene, giving the corresponding N-tosylaziridine in excellent yields and with enantiomeric excess in the range of 15−34%.

The influence of the reaction conditions on the catalytic hydrogenation of 2-aza-bicyclo hept-5-ene and oct-5-ene derivatives has been investigated. We found it possible to fully control the extent of allylic vs benzylic C−N hydrogenolysis by simple variations of H2 pressure and acidity of the reaction medium. The use of the reaction pathways was demonstrated by the selective preparation of four categories of optically active α-amino acid derivatives. The strategy was also extended to the synthesis of enantiopure α-amino ketones.

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[formula: see text] The kinetic resolution of racemic epoxides via catalytic enantioselective rearrangement to allylic alcohols was investigated. Using the Li-salt of (1S,3R,4R)-3-(pyrrolidinyl)methyl-2-azabicyclo [2.2.1] heptane 1 as catalyst allowed both epoxides and allylic alcohols to be obtained in an enantioenriched form.