Journal of the American Chemical Society
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halogenation followed by intramolecular aldol reaction with
two or three stereogenic centers in diastereoselectivity.
ASSOCIATED CONTENT
* Supporting Information
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S
Experimental procedures, compound characterization data, and
NMR spectra for new compounds. This material is available
AUTHOR INFORMATION
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Corresponding Authors
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
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This paper is dedicated to Professor Teruaki Mukaiyama in
celebration of the 40th anniversary of the Mukaiyama aldol
reaction. This work was supported by a Grant-in-Aid for
Scientific Research (No. 23225002), Advanced Catalytic
TransFormation Program for Carbon Utilization, the Uehara
Memorial Foundation, Nippon Pharmaceutical Chemicals Co.,
Ltd, and Advance Electric Co., Inc.
Figure 1. Proposed transition states of the six-membered ring aldol
product.
and OSi3 groups. Thus, C−C bond rotation occurred before
the second aldol reaction. The transition state 21 is the most
favorable, thus rationalizing the formation of the anti-syn-syn
aldol product.16
In contrast, (Z,Z)-disilyl enol ether 9 with aldehyde was
found to be anti-anti-syn stereochemistry of the five-membered
ring in intermolecular/intramolecular sequential aldol reaction
(Figure 2). For (Z,Z)-disilyl enol ether 9, the transition state
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Figure 2. Proposed transition states of the five-membered ring aldol
product.
structure 22 is favored. The first intermolecular aldol reaction
showed syn selectivity. In the second intramolecular aldol
reaction, transition states structure 23 is disfavored because of
the steric repulsions between the Lewis acid (Si2) and OSi3
groups. In this case, C−C bond rotation occurred prior to the
following cyclization. The result showed the transition state 24
is the most favorable, thus rationalizing the formation of the
anti-anti-syn aldol product.
In summary, we have developed a new strategy for a highly
diastereoselective intermolecular/intramolecular sequential
aldol reaction of disilyl enol ethers and aldehyde, and formation
of new five-, six-, and seven-membered ring aldol products. An
attractive feature of this new strategy is the ability to create four
or more contiguous stereogenic centers in a single process with
high levels of stereochemical control by super silyl groups.
Moreover, this method applied intermolecular protonation and
(5) For derivatization and single crystal X-ray analysis see Supporting
Information.
(6) The minor isomer seems to be the anti-syn-anti product by single
crystal X-ray analysis and NMR analysis.
(7) The first aldol reaction of aromatic aldehyde proceeds anti
selectivities. Please see Supporting Information for details.
(8) Ohmura, Y.; Yamamoto, Y.; Miyaura, N. Organometallics. 1999,
18, 413−416.
(9) For derivatization and single crystal X-ray analysis see Supporting
Information.
(10) For examples of protonation reactions of silyl enol ethers, see:
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