Diastereoselective reductions epoxides

The stereoselective epoxidation of chalcones, followed by acid-catalysed ring closure and concomitant cleavage of the epoxide ring, provides a very efficient route to chiral flavon-3-ols and, subsequently, by borohydride reduction to produce flavan-3,4-diols [13, 14], It has been shown that diastereoselective reduction of the chiral flavon-3-ols by sodium borohydride in methanol yields the trans-2,3-dihydroxy compounds, whereas borohydride reduction in dioxan produces the cis-isomers [14] the synthetic procedure confirms the cis configuration of the 2,3-hydroxy groups of naturally occurring leucodelphinidins [14]. 

Diazomethane is generated by the reaction of aqueous NaOH with N-methyl-N-nitroso-p-toluenesulfonamide (Diazald ) in DMSO. The diazomethane is generated quantitatively and is removed by a stream of N2 into a packed column containing a stream of mixed anhydride formed from an N-protected (BOC or CBZ) amino acid and ethyl chloroformate. The diazoketone is converted to the chloroketone using HCI, as shown in Scheme 11.10. The chiral epoxide can then be formed via diastereoselective reduction with NaBH4 and treatment with base. 

Chiral halohydrins epoxides.1 The esters (2) of the chiral alcohol 1 derived from camphor-10-sulfonic acid, are converted to a-chloro esters (3) by O-silylation and reaction with NCS with high diastereoselectivity. Reduction of 3 with Ca(BH4)2 results in the recovered auxiliary and the chlorohydrin 4 with clean retention. Cyclization of 4 to the terminal epoxide 5 proceeds with clean inversion. 

Diastereoselective reduction of chiral -keto sulfoxides (11,291-292). Chiral p-keto sulfoxides 1, prepared by reaction of p-(tolylsulfinyl)methyllithium with esters, are reduced by DIBAH in THF diastereoselectively to (R,S)-2. In the presence of ZnCl2, the opposite diastereoselectivity obtains. The paper includes a new method for conversion of these p-hydroxy sulfoxides into chiral epoxides.1... 

As for the diols, the symmetric compounds have found most uses for nonsymmetric diols, a versatile synthesis via silyl ketones using the SAMP/RAMP methodology has been developedl5. Both enantiomers of the simplest symmetric diol, 2,3-butanediol (11), are often used in asymmetric synthesis, mostly for the formation of acetals and ketals with carbonyl compounds and subsequent reactions with acidic catalysts (Section D. 1.1.2.2.), Grignard reagents (Section D. 1.3.1.4.) and other carbanions (Sections D. 1.5.1., D. 1.5.2.4.), and diastereoselective reductions (Section D.2.3.3.). Precursors of chiral alkenes for cycloprotonations (Section D.1.6.1.5.) and for chiral allenes (Section B.I.), and chiral haloboronic acids (Section D. 1.1.2.1.) are other applications. The free diol has been employed as a chiral ligand in molybdenum peroxo complexes used for enantioselective epoxidation of alkenes (Section D.4.5.2.2.). 

More recently, Simpkins has described a route to functionalized epoxides by diastereoselective reduction of racemic cychc P-ketosulfoxides (Scheme 4.7) [10]. Exclusive formation of (12a), (R = Bu, Pr DIBAL), or (12b) (R = Me, Et, Bu, Pr, Ph ZnCl2/DIBAL), could be realised by appropriate selection of reaction conditions. Preference for (12a) was rationalized by intramolecular hydride delivery from... 

Starting from (E)-27 thus prepared, one route to access epoxy alcohols (E)-24 is the diastereoselective reduction of the chiral epoxy ketones (E)-25 after enantioselective epoxidation of (E)-27 (Route A). The alternative method requires the opposite combination of the two procedures, namely, enantioselective reduction of (E)-27 to (E)-26, followed by diastereoselective epoxidation (Route B). in the case of Route A, because attachment of the carbonyl group in (E)-27 renders the C—C double-bond electron deficient, nucleophilic as5nnmetric epoxidation should be the method of choice, and enantioselective versions are available for this purpose.On the other hand, electrophilic reagents are suitable for oxirane preparation in Route B. 

Another example of diastereoselective reduction using CREDs comes from Ma-rocco et al. Using 2-chloro-3-ketophosphonate esters 70 as substrates, both cis-(1R,2S)- and (rans-( lS,2S)-epoxides were prepared according to Scheme 6.27 [41]. 

Diastereoselective reductions to access chiral cis and trans epoxides. 

Additionally, 1,2-dihydroxyethylene dipeptide analogues without the C-terminal carboxylic acid have been used to obtain aspartyl proteases inhibitors.[641 These efforts include stereoselective alkylation of imines, one-pot reductive amination of epoxy ketones, ring opening of epoxides with sodium azide, diastereoselective dihydroxylation of allylic amines, and enzymatic resolution and stereocontrolled intramolecular amidation. 

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. 

When dienones such as 55 are subjected to the epoxidation conditions the electron-poorer C=C double bond is selectively epoxidized. The other C=C bond can be functionalized further, for example, it can be dihydroxylated, as shown in the synthesis of the lactone 56 (Scheme 10.11) [82]. Stannyl epoxides such as 57 (Scheme 10.11, see also Table 10.8, R1 = n-Bu3Sn) can be coupled with several electrophiles [72], reduction of chalcone epoxide 58 and ring opening with alkyl aluminum compounds provides access to, e.g., the diol 59 and to phenylpropionic acids (for example 60). Tertiary epoxy alcohols such as 61 can be obtained with excellent diastereoselectivity by addition of Grignard reagents to epoxy ketones [88, 89]. 

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