Optimisation of enantioselectivity for the chiral base-mediated rearrangement of bis-protected meso-4,5-dihydroxycyclohexene oxides: asymmetric synthesis of 4-deoxyconduritols and conduritol F

Sousa, Simon E. de; O’Brien, Peter; Pilgram, Christopher D.

doi:10.1016/s0040-4020(02)00370-8

Cited by 36 publications

(16 citation statements)

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“…Full details of our studies in these areas are described in this paper: in particular, by careful choice of protecting group, reaction conditions and chiral base, it proved possible to obtain diastereomerically pure aziridino allylic alcohols 2 in good enantiomeric excess (47-68% ee). 18 A much simpler approach (strategy 2) involved use of allylic alcohol 4 (which can be prepared in >95% ee from epoxide trans-3 by chiral base-mediated desymmetrisation 10 ) and an investigation of ways of introducing the required nitrogen functionality. Of the methods available, we selected a direct Mitsunobu substitution with an appropriate amino source 19,20 to give allylic amines 5 and an Overman rearrangement approach 21 to give allylic amines 6.…”

Section: Introductionmentioning

confidence: 99%

Chiral lithium amide base-mediated rearrangement of meso-cyclohexene oxides: asymmetric synthesis of amino- and aziridinocyclohexenols

O’Brien

Pilgram

2003

Org. Biomol. Chem.

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Two different chiral lithium amide base routes for the synthesis of amino- and aziridino-containing cyclohexenols have been explored. The first strategy involved the diastereoselective preparation of novel meso-aziridinocyclohexene oxides and their subsequent enantioselective rearrangement using chiral bases. In this approach, the diphenylphosphinoyl nitrogen protecting group proved optimal and aziridinocyclohexenols of 47-68% ee were obtained. Of particular note was the smooth rearrangement of the epoxide to an allylic alcohol in the presence of an aziridine: under optimised chiral base conditions, the aziridine remained essentially unaffected. A second more straightforward strategy for introduction of an amino functionality was also investigated: (1S,4R,5S)- and (1R,4R,5S)-4,5-bis(tert-butyldimethylsilyloxy)cyclohex-2-enols, readily prepared in > 95% ee using a chiral base approach, were subjected to Mitsunobu substitution using a sulfonamide and Overman rearrangement.

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Section: Introductionmentioning

confidence: 99%

Chiral lithium amide base-mediated rearrangement of meso-cyclohexene oxides: asymmetric synthesis of amino- and aziridinocyclohexenols

O’Brien

Pilgram

2003

Org. Biomol. Chem.

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“…A comparison of 58 and 59 shows the beneficial effect of an adjacent stereogenic center on the stereoselectivity. Furthermore, the observed stereocontrol obtained with these two bases in a similar study performed on the bis-substituted cyclohexene oxide 60 ( Table 3) strongly suggests that the sense of induction is controlled by the benzylic stereogenic center α to the lithium amide group 58,60 . The origin of the enantiodiscrimination appears to be strongly dependent on the structure of the HCLA employed.…”

Section: B Enantioselective Access To Allylic Alcohols Via Asymmetrimentioning

confidence: 65%

Reactivity of Oxiranes with Organolithium Reagents

Chemla

Vrancken

2009

Patai's Chemistry of Functional Groups

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“…Preparatively more relevant is the use of chiral lithium amide bases, which have been successfully used both for enantioselective generation of allylic alcohols from meso-epoxides and for the related kinetic resolution of racemic epoxides [49,50]. In many instances, chiral amide bases such as 58, 59, or 60 were used in stoichiometric or over-stoichiometric quantities, affording synthetically important allylic alcohols in good yields and enantiomeric excesses (Scheme 13.28) [49][50][51][52][53][54].…”

Section: 41mentioning

confidence: 99%

Desymmetrization and Kinetic Resolution of Anhydrides; Desymmetrization of meso ‐Epoxides and other Prochiral Substrates

Berkessel

Gröger

2005

Asymmetric Organocatalysis

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Most work on this subject is based on the use of alcohols as reagents in the presence of enantiomerically pure nucleophilic catalysts [1,2]. This section is subdivided into four parts on the basis of classes of anhydride substrate and types of reaction performed (Scheme 13.1) -desymmetrization of prochiral cyclic anhydrides (Section 13.1.1); kinetic resolution of chiral, racemic anhydrides (Section 13.1.2); parallel kinetic resolution of chiral, racemic anhydrides (Section 13.1.3); and dynamic kinetic resolution of racemic anhydrides (Section 13.1.4).Desymmetrization of prochiral cyclic anhydrides: In the presence of the chiral nucleophilic catalyst (e.g. A, Scheme 13.1, top) one of the enantiotopic carbonyl groups of the prochiral (usually meso) cyclic anhydride substrate is selectively converted into an ester. Application of catalyst B (usually the enantiomer or a pseudoenantiomer of A) results in generation of the enantiomeric product ester. Ideally, 100% of one enantiomerically pure product can be generated from the starting anhydride. No reports of desymmetrizing alcoholyses of acyclic meso anhydrides appear to exist in the literature.Kinetic resolution of chiral, racemic anhydrides: In this process the racemic mixture of a chiral anhydride is exposed to the alcohol nucleophile in the presence of a chiral catalyst such as A (Scheme 13.2, middle). Under these conditions, one substrate enantiomer is converted to a mono-ester whereas the other remains unchanged. Application of catalyst B (usually the enantiomer or a pseudo-enantiomer of A) results in transformation/non-transformation of the enantiomeric starting anhydride(s). As usual for kinetic resolution, substrate conversion/product yield(s) are intrinsically limited to a maximum of 50%. For ''normal'' anhydrides (X ¼ CR 2 ), both carbonyl groups can engage in ester formation, and the product formulas in Scheme 13.1 are drawn arbitrarily. This section also covers the catalytic asymmetric alcoholysis of a-hydroxy acid O-carboxy anhydrides (X ¼ O) and of a-amino acid Ncarboxy anhydrides (X ¼ NR). In these reactions the electrophilicity of the carbonyl groups flanking ''X'' is reduced and regioselective attack of the alcohol nucleophile on the other carbonyl function results.Parallel kinetic resolution of chiral, racemic anhydrides: The term parallel kinetic resolution (PKR) implies that the two substrate enantiomers (Scheme 13.1, bottom 50 mol-% catalyst 2 CH 3 OH, toluene, r.t., 2h 7; 57 %, 76 % ee 6 Aitken et al. (refs. 7,8) Scheme 13.2 13.1 Desymmetrization and Kinetic Resolution of Cyclic Anhydrides 349 93 98 97 91 84 94 91 50 71 72 Ph Scheme 13.36 13.4 Desymmetrization of meso-Epoxides 381

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Optimisation of enantioselectivity for the chiral base-mediated rearrangement of bis-protected meso-4,5-dihydroxycyclohexene oxides: asymmetric synthesis of 4-deoxyconduritols and conduritol F

Cited by 36 publications

References 86 publications

Chiral lithium amide base-mediated rearrangement of meso-cyclohexene oxides: asymmetric synthesis of amino- and aziridinocyclohexenols

Chiral lithium amide base-mediated rearrangement of meso-cyclohexene oxides: asymmetric synthesis of amino- and aziridinocyclohexenols

Reactivity of Oxiranes with Organolithium Reagents

Desymmetrization and Kinetic Resolution of Anhydrides; Desymmetrization of meso ‐Epoxides and other Prochiral Substrates

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