Ketals asymmetric epoxidation

Compatibility of asymmetric epoxidation with acetals, ketals, ethers, and esters has led to extensive use of allylic alcohols containing these groups in the synthesis of polyoxygenated natural products. One such synthetic approach is illustrated by the asymmetric epoxidation of 15, an allylic alcohol derived from (S)-glyceraldehyde acetonide [59,62]. In the epoxy alcohol (16) obtained from 15, each carbon of the five-carbon chain is oxygenated, and all stereochemistry has been controlled. The structural relationship of 16 to the pentoses is evident, and methods leading to these carbohydrates have been described [59,62a]. 

Professor Yian Shi at the Colorado State University first reported the use of a fructose-derived chiral ketone 2 for the asymmetric epoxidation in 1996. This ketone is conveniently synthesized from an inexpensive chiral starting material D-fructose via ketalization and oxidation. The enantiomer of ketone 2, ent-2, can be prepared by the same methods from L-fructose, which is derived from L-sorbose. ... 

In 1996, Shi et al. [75] developed a fructose-derived ketone (Epoxone ) 183 as a highly effective asymmetric epoxidation catalyst. Shi s epoxidation is known to be the best for the asymmetric epoxidation of tramolefms and tri-substituted olefins. Shi s ketone is readily available and an efficient and selective oxidant that requires mild conditions. Ketone 183 could be synthesized [88] from inexpensive chiral starting material D-fructose, by ketalization and oxidation (Scheme 9.48). The enantiomer of 183 can be synthesized from L-fructose, which in turn could be obtained from commereially available L-sorbose. Chemists at DSM developed a scalable process for the preparation of Epoxone 183 in large quanities. 

In one of his most recent pubhcations, highly efficient asymmetric epoxidation of a,p-unsaturated esters has been achieved using a modified fructose catalyst [46]. It was found that the original catalyst 10 was not effective toward a,p-unsaturated esters due to its decomposition under the reaction conditions by Baeyer-Villiger oxidation. Replacement of the fused ketal in 10 with more electron withdrawing groups (acetates) produced a active and highly enantioselective catalyst (12, Scheme 1.16). 

Asymmetric elimination with high induction has mainly been described for epoxides, halides and alcohols (using chiral bases), for chiral ketals (using achiral Lewis acids), and for chiral sulfoximines (using achiral bases)1 3. For each compound class only a few examples have been examined, thus, the scope of these methods has not yet been fully explored. The literature on asymmetric eliminations up to 1970 has been covered in a review article4. 

The diols (97) from asymmetric dil droxylation are easily converted to cyclic sii e esters (98) and thence to cyclic sulfate esters (99).This two-step process, reaction of the diol (97) with thionyl chloride followed by ruthenium tetroxide catalyzed oxidation, can be done in one pot if desired and transforms the relatively unreactive diol into an epoxide mimic, ue. the 1,2-cyclic sulfate (99), which is an excellent electrophile. A survey of reactions shows that cyclic sulfates can be opened by hydride, azide, fluoride, thiocyanide, carboxylate and nitrate ions. Benzylmagnesium chloride and thie anion of dimethyl malonate can also be used to open the cyclic sulfates. Opening by a nucleophile leads to formation of an intermediate 3-sidfate aiuon (100) which is easily hydrolyzed to a -hydroxy compound (101). Conditions for cat ytic acid hydrolysis have been developed that allow for selective removal of the sulfate ester in the presence of other acid sensitive groups such as acetals, ketals and silyl ethers. 

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.). 

The absolute stereochemistry of the C-12 and C-13 oxirane moiety of laureoxolane (157), a colorless unstable bromoether obtained from extracts of Laurencia nipponica, was determined on the basis of a chiral synthesis of 156, a degradative derivative of 157. The C-5 to C-8 unit with two asymmetric centers at C-6 and C-7 of 157 corresponds to (25, 35)-l-benzyloxy-3,4-epoxy-2-butanol (142). Elongation of 142 using butyllithium and copper cyanide followed by the creation of a new epoxide provides 152. Lithium acetylide ethylenediamine complex addition to 152 and subsequent ketalization affords the acetylenic acetonide 153, which is coupled with (2i ,35)-l,2-epoxy-3-benzoyloxypentane (154) to furnish 155. Subsequent five-step transformation of 155 provides 156 [60] (Scheme 37). 

The first section of this chapter describes the preparation and several synthetic applications of a-fluoroalkyl P-sulfmyl enamines and imines the second deals with the chemistry of di- and trifluoropyruvaldehyde A, 5-ketals, stereochemically stable synthetic equivalents of P-di and P-trifluoro a-amino aldehydes, which can be prepared from the corresponding p-sulfinyl enamines the third overviews the preparation of chiral sulfinimines of trifluoropyruvate and their use to prepare a library of a-trifluoromethyl (Tfm) a-amino acids the fourth section is mainly dedicated to the asymmetric synthesis of monofluorinated amino compounds, using a miscellany of methods such as MifstmobuAike azidation of P-hydroxy sulfoxides, ring opening of fluoroalkyl epoxides with nitrogen-centered nucleophiles and 1,3-dipolar cycloadditions with chiral fluorinated dipolarophiles. 

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