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for an example of a vinylogous MBH reaction, see: d S. A. Frank, D. J. Mergott, W. R. Roush, J. Am. Chem. Soc. 2002, 124, 2404;
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for an example of a vinylogous MBH reaction, see: d) S. A. Frank, D. J. Mergott, W. R. Roush, J. Am. Chem. Soc. 2002, 124, 2404;
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h) H. Kinoshita, T. Osamura, S. Kinoshita, T. Iwamura, S.-i. Watanabe, T. Kataoka, G. Tanabe, O. Muraoka, J. Org. Chem. 2003, 68, 7532;
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29
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0022517466
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An intramolecular variant has been described involving a pendent enone; see: a K. H. Melching, H. Hiemstra, W. J. Klaver, W. N. Speckamp, Tetrahedron Lett. 1986, 27, 4799;
-
An intramolecular variant has been described involving a pendent enone; see: a) K. H. Melching, H. Hiemstra, W. J. Klaver, W. N. Speckamp, Tetrahedron Lett. 1986, 27, 4799;
-
-
-
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31
-
-
33744826542
-
-
The reaction could also be classed as a vinylogous Mannich reaction. An asymmetric Mannich reaction has been described for the synthesis of β-amino acid derivatives; see
-
The reaction could also be classed as a vinylogous Mannich reaction. An asymmetric Mannich reaction has been described for the synthesis of β-amino acid derivatives; see: Y. Chi, S. H. Gellman, J. Am. Chem. Soc. 2006, 128, 6804;
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32
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for a review of β-amino acids in biology, see
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for a review of β-amino acids in biology, see: G. Lelais, D. Seebach, Biopolymers 2004, 76, 206.
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Lelais, G.1
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33
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0037064515
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Such conditions had previously been employed for MBH reactions (usually in stoichiometric amounts) with aldehydes. See: a) L. M. Walsh, C. L. Winn, J. M. Goodman, Tetrahedron Lett. 2002, 43, 8219;
-
Such conditions had previously been employed for MBH reactions (usually in stoichiometric amounts) with aldehydes. See: a) L. M. Walsh, C. L. Winn, J. M. Goodman, Tetrahedron Lett. 2002, 43, 8219;
-
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-
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34
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0034733695
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b) T. Kataoka, H. Kinoshita, T. Iwama, S.-i. Tsuijiyama, T. Iwamura, S.-i. Watanabe, O. Muraoka, G. Tanabe, Tetrahedron 2000, 56, 4725;
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35
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0033992225
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c) G. Li, H.-X. Wei, J. J. Gao, T. D. Caputo, Tetrahedron Lett. 2000, 41, 1;
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Li, G.1
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36
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0001359326
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d) A. Itoh, S. Ozawa, K. Oshima, H. Nozaki, Bull. Chem. Soc. Jpn. 1981, 54, 274;
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Itoh, A.1
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Oshima, K.3
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37
-
-
34250791896
-
-
for other terminal electrophiles in this context, see Refs. [7e-i]; for a review, see: T. Kataoka, H. Kinoshita, Eur. J. Org. Chem. 2005, 45.
-
for other terminal electrophiles in this context, see Refs. [7e-i]; for a review, see: T. Kataoka, H. Kinoshita, Eur. J. Org. Chem. 2005, 45.
-
-
-
-
38
-
-
84982066078
-
-
It has been reported that similar adducts derived from alkyl iminium ions are stable; see: H. Boehme, M. Haake, Chem. Ber. 1972, 105, 2233
-
It has been reported that similar adducts derived from alkyl iminium ions are stable; see: H. Boehme, M. Haake, Chem. Ber. 1972, 105, 2233.
-
-
-
-
39
-
-
34250829984
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V. K. Aggarwal, J. N. Harvey, R. Robiette, Angew. Chem. 2005, 117, 5604;
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Angew. Chem
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Aggarwal, V.K.1
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40
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24644434994
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Angew. Chem. Int. Ed. 2005, 44, 5468.
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Chem. Int. Ed
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Angew1
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46549103031
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For a discussion of this issue, see the following reviews: a
-
For a discussion of this issue, see the following reviews: a) W. N. Speckamp, H. Hiemstra, Tetrahedron 1985, 41, 4367;
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Tetrahedron
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-
-
Speckamp, W.N.1
Hiemstra, H.2
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43
-
-
34250842935
-
-
When the reaction was carried out at -78°C (2 equiv of TiCl 4 and MVK, and subsequent treatment with DBU, the MBH adduct was not produced and the starting material, N,O-acetal 1, along with the hydroxy aminal derivative were recovered. This result is intriguing since Goodman and co-workers have demonstrated that the generation of the required β-chloro titanium enolate is facile at this temperature see Ref, 10a, It is possible that at -78°C, N,O-acetal 1 is converted into its kinetically stable α-chloro derivative, which only becomes unstable with respect to an iminium ion at higher temperatures, namely -20°C. When the reaction was carried out at -20°C, the MBH adduct was isolated in 67% yield. Attempts to expand the scope of the alkene beyond MVK were unsuccessful
-
4 and MVK, and subsequent treatment with DBU), the MBH adduct was not produced and the starting material, N,O-acetal 1, along with the hydroxy aminal derivative were recovered. This result is intriguing since Goodman and co-workers have demonstrated that the generation of the required β-chloro titanium enolate is facile at this temperature (see Ref. [10a]). It is possible that at -78°C, N,O-acetal 1 is converted into its kinetically stable α-chloro derivative, which only becomes unstable with respect to an iminium ion at higher temperatures, namely -20°C. When the reaction was carried out at -20°C, the MBH adduct was isolated in 67% yield. Attempts to expand the scope of the alkene beyond MVK were unsuccessful.
-
-
-
-
44
-
-
34250889687
-
-
This combination gave similar results as produced with TiCl4 alone
-
4 alone.
-
-
-
-
45
-
-
34250817816
-
-
2Al-I, which is suitably active to allow generation of the β-iodo enolate of methyl acrylate (see Ref. [10d]), did not lead to the required adduct 2g; the delivery of the ethyl rather than the enolate ligand to the iminium ion was the only process observed.
-
2Al-I, which is suitably active to allow generation of the β-iodo enolate of methyl acrylate (see Ref. [10d]), did not lead to the required adduct 2g; the delivery of the ethyl rather than the enolate ligand to the iminium ion was the only process observed.
-
-
-
-
46
-
-
0001375989
-
-
For the procedure for preparation of (S)-ethyl 2-propenethiolate, see: G. Braude, J. Org. Chem. 1957, 22, 1675.
-
For the procedure for preparation of (S)-ethyl 2-propenethiolate, see: G. Braude, J. Org. Chem. 1957, 22, 1675.
-
-
-
-
47
-
-
0021028138
-
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For previous syntheses of, -heliotridine, see: a
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For previous syntheses of (+)-heliotridine, see: a) A. R. Chamberlin, J. Y. L. Chung, J. Am. Chem. Soc. 1983, 105, 3653;
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Chamberlin, A.R.1
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0000545737
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c) G. E. Keck, E. N. K. Cressman, E. J. Enholm, J. Org. Chem. 1989, 54, 4345;
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Keck, G.E.1
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52
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1642281926
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e) J.-M. Huang, S.-C. Hong, K.-L. Wu, Y.-M. Tsai, Tetrahedron Lett. 2004, 45, 3047.
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Huang, J.-M.1
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53
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0345225165
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W. J. Klaver, H. Hiemstra, W. N. Speckamp, J. Am. Chem. Soc. 1989, 111, 2588.
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J. Am. Chem. Soc
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Klaver, W.J.1
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54
-
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33750254071
-
-
2OTf, which is a more powerful Lewis acid than its components: E. L. Myers, C. P. Butts, V. K. Aggarwal, Chem. Commun. 2006, 4434.
-
2OTf, which is a more powerful Lewis acid than its components: E. L. Myers, C. P. Butts, V. K. Aggarwal, Chem. Commun. 2006, 4434.
-
-
-
-
55
-
-
3943048796
-
-
This transformation is commonly observed when metathesis is difficult. For a review, see: B. Schmidt, Eur. J. Org. Chem. 2004, 1865
-
This transformation is commonly observed when metathesis is difficult. For a review, see: B. Schmidt, Eur. J. Org. Chem. 2004, 1865.
-
-
-
-
56
-
-
0000817736
-
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a) V. K. Aggarwal, E. Alonso, G. Hynd, K. M. Lydon, M. J. Palmer, M. Porcelloni, J. R. Studley, Angew. Chem. 2001, 113, 1479;
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33646805631
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c) V. K. Aggarwal, I. Bae, H.-Y. Lee, D. T. Williams, Angew. Chem. 2003, 115, 3396;
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V. K. Aggarwal, G. Y. Fang, C. G. Kokotos, J. Richardson, M. G. Unthank, Tetrahedron 2006, 62, 11 297. Alkylation of 8 occurs exclusively at the lone pair of electrons trans to the camphor moiety.
-
e) V. K. Aggarwal, G. Y. Fang, C. G. Kokotos, J. Richardson, M. G. Unthank, Tetrahedron 2006, 62, 11 297. Alkylation of 8 occurs exclusively at the lone pair of electrons trans to the camphor moiety.
-
-
-
-
63
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34250801861
-
-
See the Supporting Information for 1H NMR spectra of the low-temperature experiments
-
1H NMR spectra of the low-temperature experiments.
-
-
-
-
64
-
-
34250861023
-
-
eq to temperature suggests an entropy (TΔS) and enthalpy (ΔH) term which are of a similar order of magnitude.
-
eq to temperature suggests an entropy (TΔS) and enthalpy (ΔH) term which are of a similar order of magnitude.
-
-
-
|