184110-48-3Relevant academic research and scientific papers
Chiral lithium amide base-mediated rearrangement of meso-cyclohexene oxides: Asymmetric synthesis of amino- and aziridinocyclohexenols
O'Brien, Peter,Pilgram, Christopher D.
, p. 523 - 534 (2007/10/03)
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 diphenyl-phosphinoyl 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.
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
De Sousa, Simon E,O'Brien, Peter,Pilgram, Christopher D
, p. 4643 - 4654 (2007/10/03)
A strategy based on diastereoselective epoxidation of a cyclohexene followed by chiral lithium amide-mediated epoxide rearrangement has been used to synthesise an allylic alcohol building block of >95% ee. The key step is the enantioselective rearrangement of a bis-protected meso-4,5-dihydroxycyclohexene oxide. A range of protecting groups and chiral base structures were surveyed in order to find the optimum protocol for high enantioselectivity. Using a tert-butyldimethylsilyloxy protecting group and a norephedrine-derived chiral base, a 93% yield of an allylic alcohol of >95% ee was achieved. To demonstrate the synthetic utility, this allylic alcohol was subsequently transformed into 4-deoxyconduritols and (+)-conduritol F.
Chiral base route to cyclic polyols: Asymmetric synthesis of aminodeoxyconduritols and conduritol F
De Sousa, Simon E.,O'Brien, Peter,Pilgram, Christopher D.
, p. 8081 - 8083 (2007/10/03)
A chiral base route from a meso cyclohexene oxide to an allylic alcohol provides key intermediates for the synthesis of cyclic polyols. A Mitsunobu approach and an Overman rearrangement approach transform allylic alcohols into some aminodeoxyconduritols (95% ee). Elaboration of a chiral enone (89% ee) via (i) α-hydroxylation and (ii) stereoselective reduction completes a high yielding synthesis of the tetraacetate of conduritol F.
Chiral lithium amide base-mediated rearrangement of bis-protected meso-4,5-dihydroxy cyclohexene oxides: Enantioselective synthesis of (4R,5S) and (4S,5R)-4,5-bis(tert-butyldimethylsilyloxy)cyclohex-2-enone
O'Brien, Peter,Poumellec, Pierre
, p. 2435 - 2441 (2007/10/03)
The asymmetric synthesis of (4R,5S)- and (4S,5R)-4,5-bis(tert-butyldimethylsilyloxy)cyclohex-2-enone are described. Such bis-protected enones are useful intermediates in synthesis, and compounds with (4S,5R)-stereochemistry have previously been prepared from D-(-)-quinic acid. This paper reports the first synthesis of enones with (4R,5S)-stereochemistry. The route to the bis-protected enones involves chiral base-mediated rearrangement of meso-cyclohexene oxides to allylic alcohols followed by PDC oxidation. Two new chiral base reactions are described: rearrangement of a trans-epoxide generates an allylic alcohol of 76% ee (93% yield) whilst that of a cis-epoxide produces an allylic alcohol of 92% ee (38% yield); suggestions for the observed differences in yield and enantioselectivities are proposed.
Chiral base-mediated rearrangement of meso-cyclohexene oxides to allylic alcohols
O'Brien, Peter,Poumellec, Pierre
, p. 8057 - 8058 (2007/10/03)
Highly enantiomerically enriched allylic alcohols have been generated by rearranging single diastereomers of meso-cyclohexene oxides using a homochiral lithium amide base. PDC oxidation of each allylic alcohol product affords a different enantiomer of a synthetically useful cyclohexenone.
