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Volumn 14, Issue 30, 2008, Pages 9240-9254

Aldol reactions between L-erythrulose derivatives and chiral α-amino and α-fluoro aldehydes: Competition between felkin-anh and cornforth transition states

Author keywords

Aldol reaction; Boron enolates; Density functional calculations; Fluorine; Transition states

Indexed keywords

ALDEHYDES; AMINATION; AMINES; BORON; BORON COMPOUNDS; DERIVATIVES; FLUORINE; ORGANIC COMPOUNDS; ORGANIC POLYMERS;

EID: 55049109184     PISSN: 09476539     EISSN: 15213765     Source Type: Journal    
DOI: 10.1002/chem.200800956     Document Type: Article
Times cited : (20)

References (91)
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    • Other ketones structurally related to erythrulose behave in the same way: a M. Carda, J. Murga, E. Falomir, F. Gonzalez, J. A. Marco, Tetrahedron: Asymmetry 2000, 11, 3211-3220;
    • Other ketones structurally related to erythrulose behave in the same way: a) M. Carda, J. Murga, E. Falomir, F. Gonzalez, J. A. Marco, Tetrahedron: Asymmetry 2000, 11, 3211-3220;
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    • For theoretical studies on boron aldol reactions, see: a
    • For theoretical studies on boron aldol reactions, see: a) Y. Li, M. N. Paddon-Row, K. N. Houk, J. Org. Chem. 1990, 55, 481-493;
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    • For another example which shows the importance of dipole alignment in aldol transition states, see;
    • For another example which shows the importance of dipole alignment in aldol transition states, see; R. K. Boeckman Jr., B. T. Connell, J. Am. Chem. Soc. 1995, 117, 12368-12369.
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    • B does not react with pivalaldehyde, see ref. [3]. Indeed, if a TS is drawn for the aldol reaction with this aldehyde, a steric interaction of the aforementioned type will always be present for all rotamers around the tBu-CO bond.
    • B does not react with pivalaldehyde, see ref. [3]. Indeed, if a TS is drawn for the aldol reaction with this aldehyde, a steric interaction of the aforementioned type will always be present for all rotamers around the tBu-CO bond.
  • 42
    • 0034814540 scopus 로고    scopus 로고
    • The various factors which may influence the slereochemical outcome of aldol reactions have been analyzed in detail by Danishefsky and co-workers: C. B. Lee, Z. Wu, F. Zhang, M. D. Chappell, S. J. Stachel, T.-C. Chou, Y. Guan, S. J. Danishefsky, J. Am. Chem. Soc. 2001, 123, 5249-5259
    • The various factors which may influence the slereochemical outcome of aldol reactions have been analyzed in detail by Danishefsky and co-workers: C. B. Lee, Z. Wu, F. Zhang, M. D. Chappell, S. J. Stachel, T.-C. Chou, Y. Guan, S. J. Danishefsky, J. Am. Chem. Soc. 2001, 123, 5249-5259.
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    • In all discussions in this paper, no specific differentiation has been made between the purely sleric Felkin-Anh model (for aldehydes containing all-carbon substituents) and the stereoelectronic polar Felkin-Anh model for aldehydes containing α-heleroatoms
    • In all discussions in this paper, no specific differentiation has been made between the purely sleric Felkin-Anh model (for aldehydes containing all-carbon substituents) and the stereoelectronic "polar Felkin-Anh" model (for aldehydes containing α-heleroatoms):
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    • C-X orbital (for α-heteroalom-substiluted aldehydes) nor is the sterically bulkiest one (for aldehydes not containing α-heteroatoms). See also ref. [12c].
    • C-X orbital (for α-heteroalom-substiluted aldehydes) nor is the sterically bulkiest one (for aldehydes not containing α-heteroatoms). See also ref. [12c].
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    • for theoretical refinements of the model, see: b
    • for theoretical refinements of the model, see: b) M. N. Paddon-Row, N. G. Rondan, K. N. Houk, J. Am. Chem. Soc. 1982, 104, 7162-7166;
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    • Cornforth's model has been previously applied to reactions of α-oxygenated aldehydes with achiral allylboron compounds: a W. R. Roush, M. A. Adam, A. E. Walts, D. J. Harris, J. Am. Chem. Soc. 1986, 108, 3422-3434;
    • Cornforth's model has been previously applied to reactions of α-oxygenated aldehydes with achiral allylboron compounds: a) W. R. Roush, M. A. Adam, A. E. Walts, D. J. Harris, J. Am. Chem. Soc. 1986, 108, 3422-3434;
  • 58
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    • The higher stability of Cornforth-like transition structures in some additions of allylboron reagents to α-oxygenated aldehydes has also received theoretical support: B. W. Gung, X. Xue, Tetrahedron: Asymmetry 2001, 12, 2955-2959;
    • d) The higher stability of Cornforth-like transition structures in some additions of allylboron reagents to α-oxygenated aldehydes has also received theoretical support: B. W. Gung, X. Xue, Tetrahedron: Asymmetry 2001, 12, 2955-2959;
  • 59
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    • For more detailed accounts of the diastereoselective reactions of allylboron compounds, see: W. R. Roush in Comprehensive Organic Synthesis, 2 (Eds.: B. M. Trost, I. Fleming, E. Winterfeldt), Pergamon Press, Oxford, 1993 pp. 1-54, and:
    • e) For more detailed accounts of the diastereoselective reactions of allylboron compounds, see: W. R. Roush in Comprehensive Organic Synthesis, Vol. 2 (Eds.: B. M. Trost, I. Fleming, E. Winterfeldt), Pergamon Press, Oxford, 1993 pp. 1-54, and:
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    • W. R. Roush, in Houben-Weyl's Methods of Organic Chemistry, Stereoselective Synthesis, 3 (Eds: G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann), Thieme, Stuttgart, 1996, pp. 1410-1486, and references therein;
    • W. R. Roush, in Houben-Weyl's Methods of Organic Chemistry, Stereoselective Synthesis, Vol. 3 (Eds: G. Helmchen, R. W. Hoffmann, J. Mulzer, E. Schaumann), Thieme, Stuttgart, 1996, pp. 1410-1486, and references therein;
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    • for a related situation in the addition of an allenylstannane, see
    • f) for a related situation in the addition of an allenylstannane, see: J. A. Marshall, X.-J. Wang, J. Org. Chem. 1991, 56, 3211-3213.
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    • When we were performing our investigations with ketone 1, a paper by Evans and co-workers appeared in which the modified Cornforth model was applied to provide a good explanation of the sterochemical outcome of aldol reactions of achiral ketones with α-hetero-atom-substituted aldehydes: D. A. Evans, S. J. Siska, V. J. Cee, Angew. Chem. 2003, 115, 1803-1807;
    • When we were performing our investigations with ketone 1, a paper by Evans and co-workers appeared in which the modified Cornforth model was applied to provide a good explanation of the sterochemical outcome of aldol reactions of achiral ketones with α-hetero-atom-substituted aldehydes: D. A. Evans, S. J. Siska, V. J. Cee, Angew. Chem. 2003, 115, 1803-1807;
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    • Stereoselective aldol reactions with α-fluoro aldehydes (excluding α,α-difluoro aldehydes) are almost unknown. We have found only two reports in the bibliography, both of them referring to chiral α-fluoro-α-melhylaldehydes. One is the reaction of such aldehydes with achiral enolsilanes under Lewis acid catalysis: T. Yamazaki, T. Yamamoto, T. Kitazume, J. Org. Chem. 1989, 54, 83-91
    • Stereoselective aldol reactions with α-fluoro aldehydes (excluding α,α-difluoro aldehydes) are almost unknown. We have found only two reports in the bibliography, both of them referring to chiral α-fluoro-α-melhylaldehydes. One is the reaction of such aldehydes with achiral enolsilanes under Lewis acid catalysis: T. Yamazaki, T. Yamamoto, T. Kitazume, J. Org. Chem. 1989, 54, 83-91.
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    • The reactions give, however, very variable yields and show, in general, a medium-to-low stereoselectivity. They are assumed to take place through open transition states, either chelated or unchelated. The other report describes low-yielding reactions with the boron enolate of a chiral α-acyloxy ketone: S. L. Less, P. F. Leadlay, C. J. Button, J. Staunton, Tetrahedron Lett. 1996, 37, 3519-3520.
    • The reactions give, however, very variable yields and show, in general, a medium-to-low stereoselectivity. They are assumed to take place through open transition states, either chelated or unchelated. The other report describes low-yielding reactions with the boron enolate of a chiral α-acyloxy ketone: S. L. Less, P. F. Leadlay, C. J. Button, J. Staunton, Tetrahedron Lett. 1996, 37, 3519-3520.
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    • α-sulphenyl aldehydes, For nucleophilic additions to aldehydes containing other types of α-heteroatoms, see, for example: a
    • For nucleophilic additions to aldehydes containing other types of α-heteroatoms, see, for example: a) D. Enders, O. Piva, F. Burkamp, Tetrahedron 1996, 52, 2893-2908 (α-sulphenyl aldehydes);
    • (1996) Tetrahedron , vol.52 , pp. 2893-2908
    • Enders, D.1    Piva, O.2    Burkamp, F.3
  • 69
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    • Details of the preparation of aldehydes 8a, b and 9a-c as well as of the structural elucidation of the new aldols are given in the Supporting Information.
    • Details of the preparation of aldehydes 8a, b and 9a-c as well as of the structural elucidation of the new aldols are given in the Supporting Information.
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    • We did not deem it necessary to extend the study of 18B to α-amino aldehydes or to aldehydes having all-carbon α-substituents, as it has been established that aldol reactions of boron enolates of Evans oxazolidinones with such aldehydes are stereocontrolled in almost all cases by the chiral enolate. See refs, 1 and 2] and also: a K. Hayashi, Y. Hamada, T. Shioiri, Tetrahedron Lett. 1991, 32, 7287-7290;
    • B to α-amino aldehydes or to aldehydes having all-carbon α-substituents, as it has been established that aldol reactions of boron enolates of Evans oxazolidinones with such aldehydes are stereocontrolled in almost all cases by the chiral enolate. See refs. [1 and 2] and also: a) K. Hayashi, Y. Hamada, T. Shioiri, Tetrahedron Lett. 1991, 32, 7287-7290;
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    • Aldol reactions of boron enolates of Evans oxazolidinones with α-oxygenated aldehydes also are often stereocontrolled by the chiral enolate. However, at least one case is known where the strong Felkin stereofacial bias of the aldehyde overcame that of a chiral N-acyloxazolidinone and forced the formation of an anti aldol from the (Z)-boron enolate: D. A. Evans, S. W. Kaldor, T. K. Jones, J. Clardy, T. J. Stout, J. Am. Chem. Soc. 1990, 112, 7001 -7031
    • Aldol reactions of boron enolates of Evans oxazolidinones with α-oxygenated aldehydes also are often stereocontrolled by the chiral enolate. However, at least one case is known where the strong Felkin stereofacial bias of the aldehyde overcame that of a chiral N-acyloxazolidinone and forced the formation of an anti aldol from the (Z)-boron enolate: D. A. Evans, S. W. Kaldor, T. K. Jones, J. Clardy, T. J. Stout, J. Am. Chem. Soc. 1990, 112, 7001 -7031.
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    • The angles φ1 and φ2 are not defined here in the same manner as in reference [7h
    • 2 are not defined here in the same manner as in reference [7h].
  • 87
    • 55049097805 scopus 로고    scopus 로고
    • For most transition structures described here, the calculated angle of attack of the nucleophile to the carbonyl group lies in the range 97-100°. Notable exceptions were found in some transition states with fluorinated aldehydes, where the calculated angles were markedly smaller (< 95°).
    • For most transition structures described here, the calculated angle of attack of the nucleophile to the carbonyl group lies in the range 97-100°. Notable exceptions were found in some transition states with fluorinated aldehydes, where the calculated angles were markedly smaller (< 95°).
  • 88
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    • 2 = 0) of ex-oxygenated aldehydes, see; B. Lecea, A. Arrieta, F. P. Cossío, J. Org. Chem. 1997, 62, 6485-6492, and references therein.
    • 2 = 0) of ex-oxygenated aldehydes, see; B. Lecea, A. Arrieta, F. P. Cossío, J. Org. Chem. 1997, 62, 6485-6492, and references therein.
  • 89
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    • After these results were obtained, the calculations were repeated for α-alkoxy aldehydes (R)- and (S)-23b and a model ketone enolate i, closer to the actual reagent 1. However, the results were essentially the same as with 22 and therefore the calculations were not continued with the other aldehydes.
    • After these results were obtained, the calculations were repeated for α-alkoxy aldehydes (R)- and (S)-23b and a model ketone enolate i, closer to the actual reagent 1. However, the results were essentially the same as with 22 and therefore the calculations were not continued with the other aldehydes.


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