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Volumn 70, Issue 20, 2005, Pages 8130-8139

Double diastereoselection in aldol reactions mediated by dicyclohexylchloroborane between chiral aldehydes and a chiral ethyl ketone derived from L-erythrulose. Synthesis of a C1-C9 fragment of the structure of the antifungal metabolite soraphen A1α

Author keywords

[No Author keywords available]

Indexed keywords

FUNGI; KETONES; METABOLITES; STEREOCHEMISTRY;

EID: 25444486183     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo051307p     Document Type: Article
Times cited : (19)

References (110)
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    • This stereochemical outcome of aldol reactions mediated by dicyclohexylboron chloride may be general in α-oxygenated ketones: Murga, J.; Falomir, E.; Carda, M.; González, F.; Marco, J. A. Org. Lett. 2001, 3, 901-904.
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    • 7 we assumed that the not isolated, minor stereoisomer was the "anti-Felkin" stereoisomer, which resulted from attack to the aldehyde Si face. However, we later found that aldehyde 5b is much more prone to racemization than its analogue 5a. We thus believe that the minor stereoisomer, which appears in the reaction mixture in variable proportions, is formed from the small proportion of the undesired enantiomer, generated adventitiously during the synthesis and isolation of the aldehyde. The preparation of aldehydes 5 has to be performed with extreme care, to keep racemization to a minimum (the results presented in this paper and in refs 7 and 9 are part of the Ph.D. thesis of S.D.-O., Universidad Jaume I, July 2005).
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    • Shortly before we concluded our investigation with ketone 1, a paper by Evans and co-workers appeared in which the Cornforth model was resurrected to provide a good explanation of the sterochemical outcome of aldol reactions of achiral ketones with α-heteroatom-substituted aldehydes: Evans, D. A.; Siska, S. J.; Cee, V. J. Angew. Chem., Int. Ed. 2003, 42, 1761-1765.
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    • Cornforth's model has been previously applied to reactions of α-oxygenated aldehydes with achiral allylboron compounds: (a) Roush, W. R.; Adam, M. A.; Walts, A. E.; Harris, D. J. J. Am. Chem. Soc. 1986, 108, 3422-3434.
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    • 7 Because aldehydes 6c gave essentially the same results as 6b in aldol reactions with 1, only the latter were used in the present work.
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    • 17 Standard manipulations of the protecting groups further permitted the preparation of other cyclic derivatives suitable for similar NMR studies. Descriptions of these chemical correlations and analytical data for correlation products are given in the Supporting Information.
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    • The stereostructures of two correlation compounds related to aldols 10a and 11a (see Supporting Information) were established by means of X-ray diffraction analyses. Crystallographic data (excluding structure factors) have been deposited at the Cambridge Crystallographic Data Center as supplementary material with references CCDC-269222 and CCDC-269772. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge, CB2 1EZ, UK [fax, +44(0)-1223-336033 or e-mail, deposit@ ccdc.cam.ac.uk].
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    • In our first approach to 13, MOM protecting groups were used for the hydroxyl functions of diol 14. However, they proved incompatible with the acidic reaction conditions necessary for the deprotection of the cyclohexanone acetal: a great amount of decomposition was observed under a variety of conditions, as well as formation of formaldehyde acetals as byproducts.
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    • At least one case is known where the strong Felkin stereofacial bias of an α-oxygenated aldehyde forced the formation of an anti aldol from the Z-boron enolate of a chiral N-acyloxazolidinone: Evans, D. A.; Kaldor, S. W.; Jones, T. K.; Clardy, J.; Stout, T. J. J. Am. Chem. Soc. 1990, 112, 7001-7031. In the present case, however, a matched double diastereoselection can be expected between the known facial preference of the boron enolate of 21 and the Felkin bias of aldehyde 20: both factors predict here a predominant enolate attack to the aldehyde carbonyl Si face. For a very similar situation, see ref 29b.
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    • 3 or Li di-tert-butyldiphenylide) are precluded here due to the presence of the α-alkoxy ketone moiety. We are presently investigating other methods to improve the yield of this critical deprotection step, as well as the use of alternative protecting groups.


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