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C. F, III. In Modern Aldol Reactions; Marhrwald, R., Ed.; Wiley-
synthetic utility of organocatalytic direct aldol reactions.
Further investigations into the mechanistic aspects and
the use of new organocatalysts for this reaction are under-
way and will be reported in due course.
`
VCH: Weinheim, 2004; Vol. 1, Chapter 6; (f) Guillena, G.; Najera, C.;
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G.; Fan, J.; Barbas, C. F., III. Tetrahedron Lett. 2004, 45, 5681–5684;
(e) Maggiotti, V.; Bahmanyar, S.; Reiter, M.; Resmina, M.; Houk, K.
N.; Gouverneur, V. Tetrahedron 2004, 60, 619–632.
20. (a) Tokuda, O.; Kano, T.; Gao, W.-G.; Ikemoto, T.; Moruoka, K.
Org. Lett. 2005, 7, 5103–5105; (b) Luppi, G.; Cozzi, P. G.; Monari,
M.; Kaptein, B.; Broxterman, Q. B.; Tomasini, C. J. Org. Chem.
2005, 70, 7418–7421; (c) Samanta, S.; Zhao, C.-G. Tetrahedron Lett.
2006, 47, 3383–3386; (d) Wang, Y.-J.; Shen, Z.-X.; Li, B.; Zhang, Y.-
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Acknowledgements
`
Financial support from the Ministero dell’Universita e
della Ricerca Scientifica e Tecnologica, Rome, and by the
University of Cagliari (National Project ‘Stereoselezione
in Sintesi Organica, Metodologie ed Applicazioni’) and
from CINMPIS is gratefully acknowledged.
Supplementary data
Supplementary data (Experimental procedures and ana-
lytical data for all new compounds) associated with this
article can be found, in the online version, at doi:
`
1263–1266; (g) Guillena, G.; Hita, M.; Najera, C. Tetrahedron:
Asymmetry 2006, 17, 1027–1031; (h) Wang, X.-J.; Zhao, Y.; Liu, J.-T.
Org. Lett. 2007, 9, 1343–1345; (i) Xu, X.-Y.; Tang, Z.; Wang, Y.-Z.;
Luo, S.-W.; Cun, L.-F.; Gong, L.-Z. J. Org. Chem. 2007, 72, 9905–
9913.
21. A typical procedure for the reaction of aldehydes with phenylthio-
and phenoxyacetone is as follows: To a mixture of anhydrous DMSO
(20 mL) and ketone donor (5 mL) was added the corresponding
aldehyde (4.4 mmol) followed by the catalyst (20 mol %) and the
resulting mixture was stirred at room temperature for 96 h. The
reaction mixture was poured into saturated ammonium chloride
solution, the layers were separated and, the aqueous phase was
extracted several times with diethyl ether. The combined organic
extracts were dried with anhydrous Na2SO4 and evaporated to afford
the crude aldol adducts. The residue was purified by flash chroma-
tography (silica gel, light petroleum–diethyl ether 1:1). 4-Hydroxy-4-
(4-nitrophenyl)-3-phenoxybutan-2-one (4a): Orange oil. Yield 65%. IR
References and notes
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(neat): 3500, 1720, 1517, 1347 cmꢀ1 1H NMR (300 MHz, CDCl3) d:
.
2.15 (s, 3H), 3.22 (d, 1H, J = 3.6 Hz), 4.63 (d, 1H, J = 6 Hz), 5.25–
5.27 (m, 1H), 6.75–6.79 (m, 2H), 6.99 (t, 1H), 7.21–7.33 (m, 2H), 7.61
(d, 2H), 8.20 (d, 2H). 13C NMR (75 MHz, CDCl3) d: 27.5, 73.3, 85.4,
114.9, 122.4, 123.4, 127.6, 129.9, 146.1, 157.0, 208.7. MS: m/z
(%) = 283 (M+ꢀ18 (5)), 212 (3), 154 (4), 133 (8), 89 (12), 77 (48), 63
26
(16), 51 (28), 43 (100). ½aꢁD +2.7 (c 0.36, CH2Cl2), 84% ee. The ee was
determined by HPLC on a Chiralcel OD-H column with hexane–
i-PrOH (80:20) as the eluent, flow rate 1 mL/min, k = 254 nm. tR
(major): 7.4 min, tR (minor): 8.4 min. Anal. Calcd for C16H15NO5: C,
63.78; H, 5.02; N, 4.65. Found: C, 63.7; H, 5.06; N, 4.69.
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temperature for
a certain time and the reaction progress was
monitored by TLC. The reaction mixture was poured into saturated
ammonium chloride solution, the layers were separated and, the
aqueous phase was extracted several times with diethyl ether. The
combined organic extracts were dried with anhydrous Na2SO4 and
evaporated to afford the crude aldol adducts. The residue was purified
by flash chromatography (silica gel, light petroleum–diethyl ether 1:1).
4-Hydroxy-5-phenoxy-4-((phenylsulfonyl)methyl)pentan-2-one (5e):
.
Orange oil. Yield 60%. IR (neat): 3400, 1720, 1340, 1150 cmꢀ1 1H
NMR (300 MHz, CDCl3) d: 2.26 (s, 3H), 3.22 (ABq, 2H, J = 17.7 Hz,
J = 36 Hz), 3.66 (ABq, 2H, J = 14.4 Hz, J = 30.3 Hz), 4.09 (d, 2H,