Enantiomerically pure epoxide

An effective deoxygenation using enantiomerically pure epoxides from primary allylic alcohols ( Sharpless epoxides ) [44] to give enantiomerically pure secondary allylic alcohols was described by Yadav [45]. This approach circumvented a kinetic resolution of secondary allylic alcohols that implies a maximum yield of 50% ( Scheme 5). 

Recently, Italian researchers have developed a new procedure for the synthesis of five-membered cyclic nitronates with the use of enantiomerically pure epoxides (65-67) and aziridines (68) as the starting substrates (15) (Scheme 3.18, see also substrate B in Scheme 3.11, Eq. 1). 

Optically pure tri(hydroxyalkyl)amines 29 (R = Me, t-Bu, cyclohexyl or Ph) have been obtained from enantiomerically pure epoxides and methanolic ammonia63. Tetraphenylsti-bonium trifluoromethanesulphonate, SbPhzj1 C.f 3S03, catalyses the reaction of epoxides with amines, e.g. diethylamine or aniline, to yield 2-hydroxyalkylamines in quantitative yields (equation 25)64. 

Scheme 22. ARO of enantiomerically pure epoxide with various indoles using catalyst 51.

Scheme 23. Reaction for Thiolysis of enantiomerically pure epoxide mediated by 51,...

Enantiomerically pure epoxides and diols, readily available through the asymmetric epoxidation and asymmetric dihydroxylation reactions, are ideal precursors to prepare cis-amino alcohols via the Ritter reaction. " " A Merck group has shown that indene oxide 175a can be converted effectively to c/i-l-amino-2-indanol, a key fragment of the HlV-protease inhibitor Indinavir via the cis-... 

Conversion to the R-hydroxyester set the stage for the synthesis of an enantiomerically-pure epoxide, a versatile C-4 building block (Eq. 110) [301]. 

The selective reduction of 5 suggests that 9 and/or 12 might reduce with high enantioselectivity. This would open an inexpensive route to enantiomerically-pure epoxides, important intermediates for organic synthesis. 

In Communications submitted two weeks apart, David W.C. MacMillan of Caltech (7. Am. Chem. Soc. 2004,126,4108) and Karl Anker Jorgensen of Aarhus University, Denmark (7. Am. Chem. Soc. 2004, /26,4790) reported the enantioselective a-chlorination of aldehydes, using organocatalysts 14 and 15 respectively. The chloro aldehydes are promising precursors to, inter aliay enantiomerically-pure epoxides. 

Polyhydroxylated piperidines such as are of interest as glucosidase inhibitors. Antoni Riera, also of the University of Barcelona, has developed (J. Org. Chem. 2005, 70,2325) a route to 16 from the readily-available enantiomerically-pure epoxide 11. Condensation with ally isocyanate 12 followed by cyclization gave 13, which was further cyclized by a Grubb s catalyst (unspecified) to 14. Protection set the stage for face-selective dihydroxylation, to give 15. Several other piperidines having other polyhydroxylation patterns were also prepared from 14. 

Johnson in 1993 described an approach to racemic p-amyrin involving application of a biomimctic polyene cyclization.7 In the same year Corey accomplished the enantioseleetive synthesis of compound 4. a key intermediate that opened the way to stereoselective preparation of compounds I, 2. and 3 8 A key step in the synthesis of P-amyrin (1) was the introduction of chiral oxazaboroli-dines for enantioseleetive carbonyl reduction. Ba ed on these methods, generation of an enantiomerically pure epoxide and its stereoselective cationic cyclization led to the pentacyclic system of structure 1 Diastereoselective cyclopropanation and an intramolecular protonation of a carbanion represent other interesting steps in this total synthesis. 

Smith et al. have developed a very elegant route to complex polyol structures by sequential dithiane-epoxide coupling reactions (Scheme 7) [16]. Following the work of Tietze [17], 2-silyl-1,3-dithianes 42 are deprotonated with /BuLi in ether and converted into the stable lithium alk-oxides 43 with enantiomerically pure epoxides. A fast 1,4-Brook rearrangement occurs only after the addition of 0.3 equivalents of hexamethyl-phosphoramide (HMPA) or 1,3-dimethylhexahy-dro-2-pyrimidone (DMPU) to the reaction mixture. A new lithiated dithiane 44 that can undergo... 

Analogous reactions of acyclic vinyl epoxides 15 with 4-toluenesulfonyl isocyanate also proceed with complete retention of configuration55. Enantiomerically pure epoxides such as 15b and c are readily available and reductive removal of the 4-toluenesulfonyl substituent from 16 is easily achieved. The transformation of 15c to 2-oxazolidinone 16c was used as the key conversion in a short enantioselective synthesis of acosamine55. 

The importance of optically active vicinal thio- and selenoalcohols has been recognized as potential intermediates for enantiomerically pure epoxides, which have been used in the synthesis of more complex enantiomerically enriched compounds [54]. The synthesis of racemic vicinal thio- and selenoalcohols via stereoselective reduction of a-thio- [55] and a-selenoketones [56] has been reported, whereas very few asymmetric syntheses of highly optically active vicinal thioalcohols are known [57]. 

Racemic hydroxy ester 225 was converted, via a Sharpless kinetic resolution, to the enantiomerically pure epoxide 226. This epoxide was then converted to the diol "/-lactone by intramolecular attack of the ester, assisted by nucleophilic dealkylation with iodide ion. Deprotonation and methylation anti to the alkoxide followed by acetonide formation afforded 227 in 56% yield. Dibal reduction, protection of the resulting aldehyde as the terminal olefin, silylation of the tertiary alcohol, and liberation of the aldehyde via ozonolysis provided a 45% yield of the C-9 to C-15 fragment 228. 

Alternatively, an enantiomerically pure catalyst that is not an enzyme can be used to obtain an enantiomerically pure target molecule. For example, an enantiomerically pure epoxide of an allylic alcohol can be prepared by treating the alcohol with tert-butyl hydroperoxide, titanium isopropoxide, and enantiomerically pure diethyl tartrate (DET). The structure of the epoxide depends on the enantiomer of diethyl tartrate used. 

This method, developed in 1980 by Barry Sharpless, has proven to be useful for the synthesis of a wide variety of enantiomerically pure compounds, because an epoxide can easily be converted into a compound with two adjacent asymmetric carbons, since epoxides are very susceptible to attack by nucleophiles. In the following example, an allylic alcohol is converted into an enantiomerically pure epoxide, which is used to form an enantiomerically pure diol. 

What is the product of the reaction of methylmagnesium bromide with either of the enantiomerically pure epoxides that can be prepared from ( )-3-methyl-2-pentene by the preceding method Assign R or S configurations to the asymmetric carbons of each product. 

Ring opening of the enantiomerically pure epoxide 188 (from reduction of 187) with labeled methyllithium has been used as the key step in a synthesis... 

The preparation of 1 started with the addition of lithiated 4 to the enantiomerically-pure epoxide 5, which was prepared from the racemate using the Jacobsen protocol. Reduction followed by. selective protection of the primary alcohol gave the monosilyl ether, which was further protected with MOM chloride to give 7. Pd-mediated oxidation to the methyl ketone followed by condensation with the Horner-Emmons reagent gave the unsaturated ester 8 as an inconsequential mixture of geometric isomers. Oxidation then set the stage for the cmcial cyclization. 

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