Epoxides Stereoselective synthesis

Stereoselective synthesis of epoxides andaziridines viaylide routes 99PAC369. 

Jackson and coworkers have used a new approach to the synthesis of fi-hydtoxy-ct-amino acids using farylthio nitrooxiranes. c-Jsopropylideneglyceraldehyde is converted into the corresponding 1-arylthio-l-nitroalkene, which is a key material for stereoselective synthesis of fi,Y-dihydroxyamino acids fScheme 4.6. The key step is stereoselective nucleophilic epoxlda-donof the Tarylthio-Tnltroalkene. Sy)i and ruin epoxides are selecdvely obtained by appropriate choice of epoxidadon reagent." ... 

The advantages of allylchromium reagents in stereoselective synthesis were soon shown7 8- 9. Due to mild reaction conditions, sensitive functionalities - even epoxide rings10 -... 

Since the seminal contributions by Nugent and RajanBabu the field of reductive C - C bond formation after epoxide opening via electron transfer has developed at a rapid pace. Novel catalytic methodology, enantio- and stereoselective synthesis and numerous applications in the preparation of biologically active substances and natural products have evolved. In brief, a large repertoire of useful and original reactions is available. These reactions are waiting to be applied in a complex context ... 

The stereoselective synthesis of awri-P-amino-a-hydroxy acid derivatives using nucleophilic epoxidation of 1-arytlthio-l-nitroalkenes has been reported (Eq. 4.41).54... 

A much more elaborate synthesis of 4-aryl-2-(benzyloxy)carbonyl-3-hydroxy tetrahydrofurans 88 from aryl epoxides requires the use of benzyl diazoacetate. This methodology can now be extended to a highly stereoselective synthesis of chiral tetrahydrofurans starting from optically active epoxides. The mechanism is believed to involve a Williamson-type cyclization as illustrated below <00TL8059>. 

In addition, Wipf and co-workers104 have used silver(i)-catalyzed addition of zirconocenes to 3,4,6-tri-O-benzyl-D-glucal epoxide 93 for the stereoselective synthesis of a-C-glucosyl compounds 95 and 96 following a similar mechanism as in the reaction with organoaluminium and organoboron reagents (Scheme 32). 

A similar enzyme-catalyzed stereoselective synthesis of enantiomers of propanolamines has been recently reported30. Addition of a lipozyme from the fungus Mucor miehei to the epoxide ( )-8 in toluene and then a slightly more than one half molar equivalent of 2-propylamine gave a 29% conversion of ( )-8 to (S)-9 with an ee of 90%. For some benzene ring-substituted epoxides, both the percent conversion of the epoxide and the ee of product are slightly higher30. 

A -tritylaziridine-2-(5)-carboxaldehyde. The application of a novel, sequential, trans-acetalation oxonium ene cyclization has delivered a stereoselective synthesis of the C-aromatic taxane skeleton, and a combinatorial sequence of the regioselective propiolate-ene, catalytic enantioselective epoxidation and carbonyl-ene cyclization reactions has been used to complete the synthesis of the A-ring of a vitamin D hybrid analogue. 

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-... 

The authors also investigated the mode of activation of these BINOL-derived catalysts. They proposed an oligomeric structure, in which one Ln-BINOL moiety acts as a Brpnsted base, that deprotonates the hydroperoxide and the other moiety acts as Lewis acid, which activates the enone and controls its orientation towards the oxidant . This model explains the observed chiral amplification effect, that is the ee of the epoxide product exceeds the ee of the catalyst. The stereoselective synthesis of cw-epoxyketones from acyclic cw-enones is difficult due to the tendency of the cw-enones to isomerize to the more stable fraw5-derivatives during the oxidation. In 1998, Shibasaki and coworkers reported that the ytterbium-(f )-3-hydroxymethyl-BINOL system also showed catalytic activity for the oxidation of aliphatic (Z)-enones 129 to cw-epoxides 130 with good yields... 

Preparation of nonracemic epoxides has been extensively studied in recent years since these compounds represent useful building blocks in stereoselective synthesis, and the epoxide functionality constitutes the essential framework of various namrally occurring and biologically active compounds. The enantiomericaUy enriched a-fluorotropinone was anchored onto amorphous KG-60 silica (Figure 6.6) this supported chiral catalyst (KG-60-FT ) promoted the stereoselective epoxidation of several trans- and trisubstituted alkenes with ees up to 80% and was perfectly reusable with the same performance for at least three catalytic cycles. 

Babler and Schlidt [86] described a route to a versatile C15 phosphonate, used for a stereoselective synthesis of all E retinoic acid and p-carotene. Base-catalyzed isomerization of the vinyl-phosphonate afforded the corresponding allyl-phosphonate as the sole product. Homer-Emmons olefination with ethyl 3-methyl-4-oxo-2-butenoate concluded the facile synthesis of all E ethyl retinoate. The C15 phosphonate was synthesized starting from the epoxide of P-ionone. Subsequent isomerization with MgBr2, afforded the C14 aldehyde in 93%... 

Reduction of the carbonyl in the r >[CO-CH2-NH] link 7 (R1 = H) results in the (hy-droxy)ethyleneamino or r >[CH(OH)-CH2-NH] link 8 (R1 = H), which has proved to be a very potent analogue of the tetrahedral hydrated intermediate of the scissile amide bond. It has been widely used for the design of various inhibitors of HIV protease 141,142 14 154 and ACE, 155-157 and to synthesize angiotensin II, III, and IV analogues. 158,159 Indeed, the chirality of the hydroxylated carbon is critical for HIV protease inhibition, but separation of the epimers may be difficult. Therefore, the stereoselective synthesis from epoxides has been actively investigated. An example of a C-methylated tp[CMe(OH)-CH2-NH] link, obtained from an epoxide with chromatographic separation of the epimers, has also been described. 157 Most of the [(hydroxy)ethyleneamino] peptides have been prepared by solution procedures, but two examples of solid-phase synthesis have been reported. A theoretical study of the (hydroxy)ethyleneamino replacement for the amide bond has been carried out on a HIV protease inhibitor. 160 ... 

Another approach in the study of the mechanism and synthetic applications of bromination of alkenes and alkynes involves the use of crystalline bromine-amine complexes such as pyridine hydrobromide perbromide (PyHBts), pyridine dibromide (PyBn), and tetrabutylammonium tribromide (BiMNBn) which show stereochemical differences and improved selectivities for addition to alkenes and alkynes compared to Bn itself.81 The improved selectivity of bromination by PyHBn forms the basis for a synthetically useful procedure for selective monoprotection of the higher alkylated double bond in dienes by bromination (Scheme 42).80 The less-alkylated double bonds in dienes can be selectively monoprotected by tetrabromination followed by monodeprotection at the higher alkylated double bond by controlled-potential electrolysis (the reduction potential of vicinal dibromides is shifted to more anodic values with increasing alkylation Scheme 42).80 The question of which diastereotopic face in chiral allylic alcohols reacts with bromine has been probed by Midland and Halterman as part of a stereoselective synthesis of bromo epoxides (Scheme 43).82... 

The final step in Danishefsky s synthesis of the sesquiterpene coriolin (2)3 required bis epoxidation of 1. All attempts to effect this reaction in one step resulted in a mixture of the desired diepoxide (2) and epicoriolin (3) in about equal parts under best conditions. However, a two-step epoxidation procedure (1 >4 and 5 ->-6) resulted in a stereoselective synthesis of 2. 

The stereoselective synthesis of (+)-polyoxin J is accomplished by Gosh in 24 steps and 3 % overall yield. The key intermediates are protected thymine polyoxin C 8 and the 5-Ocarbamoyl polyoxamic acid 2, which were synthesized from D-ribose and dimethyl L-tartrate. Key steps are two different epoxidation reactions, one carried out with MCPBA and the other under Sharpless conditions with the D-(-)-tartrate. Both epoxides are opened with diisopropoxytitanium diazide. The coupling of the two fragments was realized with the BOP reagent 37. This synthesis provides an easy access to the synthesis of various (+)-polyoxin J analogs for biological evaluation. 

Chini, M. Crotti, P. Gardelli, C. Macchia, F. Regio- and stereoselective synthesis of / -halo-hydrins from 1,2-epoxides with ammonium... 

Bell, T. W. and Ciaccio, J.A. (1988). Alkylative epoxide rearrangement, application to stereoselective synthesis of chiral pheromone epoxides. Tetrahedron Lett., 29, 865-868. 

R. Schwesinger, J. Willaredt, T. Bauer, A. C. Oehlschlager, Formation of C-O Bonds by Epoxidation of Olefinic Double Bonds, in Methoden Org. Chem. (Houben-Weyl) 4th ed. 1952-, Stereoselective Synthesis (G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann, Eds.), Vol. E2 le, 4599, Georg Thieme Verlag, Stuttgart, 1995. 

The lithium derivative of the chiral chelating diamine (3 )-2-(l-pyrrolidinylmethyl)-pyrrolidine (6) has been used extensively in stereoselective synthesis, i.e. in the deprotonation of ketones and rearrangement of epoxides to homoallylic alcohols. The lithium amide has been crystallized from toluene solution, and X-ray analysis revealed that it forms a ladder-type tetramer with the two pyrrolidine nitrogens solvating the two lithiums at the end of the ladder38, (Li-6)4. 

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