Grignard-type carbonyl phenylation in water and under an air atmosphere [1]

Full text of DOI:10.1021/ja001699b

9538
J. Am. Chem. Soc. 2000, 122, 9538-9539
Communications to the Editor
Grignard-Type Carbonyl Phenylation in Water and
under an Air Atmosphere
Table 1. Rhodium-Catalyzed Reaction of Trimethylphenylstannane
with Aldehyde in Water
Chao-Jun Li* and Yue Meng
Department of Chemistry, Tulane UniVersity
New Orleans, Lousiana 70118
ReceiVed May 17, 2000
Due to the natural abundance of water as well as the inherent
advantages of using water as a solvent, recently interest has been
growing in studying organic reactions in water. Many reactions
that are traditionally carried out in organic solvent can be carried
1
out in water with additional interesting features. Carbon-carbon
2
bond formation is the essence of organic synthesis. One of the
most important methods for forming carbon-carbon bonds is
through the nucleophilic addition of an organometallic reagent
to a carbonyl derivative. Such reactions are exemplified by the
3
Barbier-Grignard type reactions. For carbonyl additions based
on organometallic reagents, it is generally accepted that strict
anhydrous reaction conditions are required for a smooth reaction.4
On the other hand, the significance of performing metal-
mediated reactions in water has been recognized recently. Within
the last several years, various metals have been developed to
mediate Barbier-Grignard type reactions. Recent studies have
shown the advantages using aqueous organometallic reactions over
those occurring in organic solvent in organic synthesis. For
instance, the protection-deprotection processes for certain acidic-
hydrogen-containing functional groups can be avoided, which
contributes to an overall synthetic efficiency. Water-soluble
compounds, such as carbohydrates, can be reacted directly without
the need for derivatization, and water-soluble catalyst solutions
can be reused for a prolonged period of time which reduces
5
6
operational cost. However, while the allylation, propargylation,
7
8
aldol-type reaction, and benzylation of carbonyl compounds has
been successful with various metals including magnesium in
9
water, a successful Grignard-type reaction with nonactivated
halides in water is yet to be developed.
(
1) For general reviews on organic reactions in water, see: Li, C. J.; Chan,
T. H. Organic Reactions in Aqueous Media; John Wiley & Sons: New York
997. See also: Li, C. J.; Chan, T. H. Tetrahedron 1999, 55, 11149; Li, C.
1
J. Chem. ReV. 1993, 93, 2023. Li, C. J. Tetrahedron 1996, 52, 5643. Chan, T.
H.; Isaac, M. B. Pure Appl. Chem. 1996, 68, 919. Lubineau, A.; Auge, J.;
Queneau, Y.; Lubineau, A.; Auge, J.; Queneau, Y. Synthesis 1994, 741.
Organic Synthesis in Water; Grieco, P. A. Ed.; Blackie Academic &
Professional: Glasgow, 1998. Cornils, B.; Wiebus, E. Chemtech 1995, 25(1),
3
3
3. Hermann, W. A.; Kohlpainter, C. W. Angew. Chem., Int. Ed. Engl. 1993,
2, 1524. Kuntz, E. G. Chemtech 1987, 17(9), 570.
a
(
2) Corey, E. J.; Cheng, X. M. The Logic of Organic Synthesis; John Wiley
Sons: New York, 1989.
3) Kharasch, M. S.; Reinmuth, O. Grignard Reactions of Nonmetallic
All reactions were carried out in deionized water under an
&
atmosphere of air and at 110 °C (oil bath temperature). Yields were
isolated ones after flash chromatography on silica gel. Nearly the same
result was obtained when tributylphenyltin was used for entry 1.
(
Substances; Prentice-Hall: New York, 1954. Barbier, P. Compt. rend. 1898,
28, 110. Barbier, P. J. Chem. Soc. 1899, 76, Pt. 1, 323. Grignard, V. Compt.
rend. 1900, 130, 1322.
1
This is largely due to the fact that it requires a highly reactive
metal to break a nonactivated carbon-halogen bond (as well as
to react with the carbonyl once the organometallic intermediate
is formed) and, with a highly reactive metal, various competing
side-reactions (such as the reduction of water, the reduction of
starting materials, and the hydrolysis of the organometallic
intermediate, even if it is successfully generated) will prevail.
This seems like an insurmountable dilemma (as judged by the
numerous failed attempts of our own) that restricts the further
development of aqueous organometallic reactions. Herein we wish
to report a design that shows promise in overcoming such a
(
4) Wakefield, B. J. Organomagnesium Methods in Organic Synthesis, Best
Synthetic Methods series; Katritzky, A. R., Meth-Cohn, O., Rees, C. W., Eds.;
Academic Press: San Diego, 1995.
(
5) Paquette, L. A. In Green Chemistry: Frontiers in Benign Chemical
Syntheses and Processes; Anastas, P. A., Williamson, T. C., Eds.; Oxford
University Press: Oxford, UK, 1998.
(6) Isaac, M. B.; Chan, T. H. J. Chem. Soc., Chem. Commun. 1995, 1003.
Yi, X. H.; Meng, Y.; Hua, X. G.; Li, C. J. J. Org. Chem. 1998, 63, 7472.
7) Chan, T. H.; Li, C. J.; Wei, Z. Y. J. Chem. Soc., Chem. Commun. 1990,
05. Shen, Z.; Zhang, J.; Bieber, L. W.; Malvestiti, I.; Storch, E. C. J. Org.
Chem. 1997, 62, 9061. Zou, H.; Yang, M. Tetrahedron Lett. 1997, 38, 2733.
8) Bieber, L. W.; Storch, E. C.; Malvestiti, I.; Sila, M. F. Tetrahedron
Lett. 1998, 39, 9393.
9) Li, C. J.; Zhang, W. C. J. Am. Chem. Soc. 1998, 120, 9102.
(
5
(
(
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0.1021/ja001699b CCC: $19.00 © 2000 American Chemical Society
Published on Web 09/13/2000

Communications to the Editor
J. Am. Chem. Soc., Vol. 122, No. 39, 2000 9539
dilemma, in which the first Grignard-type phenylation of alde-
hydes in water has been developed. In the presence of a catalytic
amount of Rh(COD) BF , phenyltin derivatives (trimethyl and
2 4
Scheme 1. Proposed Mechanism for the Rhodium-Catalyzed
Addition of Aryl Stannanes to Aldehydes in Water
10
tributyl) react effectively with aldehydes in water and under an
atmosphere of air to give nucleophilic addition products in high
yields (eq 1).
To begin our study, phenyltrimethylstannane was stirred with
benzaldehyde and a catalytic amount of a rhodium catalyst (5
mol %) at room temperature in water. No reaction was observed
even after several days. However, when the reaction was carried
out under refluxing conditions, a smooth reaction occurred to give
a clean product overnight as judged by GC-MS and TLC. The
GC-MS analysis also indicated the formation of the desired
product. Subsequently, isolation and characterization confirmed
the structure of the nucleophilic addition product. Various
aldehydes were thus converted to the corresponding alcohols
similarly (Table 1). The presence of NaF improved the reaction
yield slightly. Phenyltributylstannane is equally effective in
serving as the nucleophile. Aryl halides (such as chloride, fluoride,
and bromide) are inert under the present reaction conditions which
imparts chemoselectivity. The presence of electron-withdrawing
and potentially reactive cyano and hydroxyl groups did not
adversely interfere with the reaction. Aliphatic aldehydes are also
effective in reacting with the tin reagent, although the yields of
the desired products were slightly lower. Scheme 1 outlines a
tentative mechanism in which rhodium serves as a catalyst for
the addition. In conclusion, the first successful aqueous Grignard-
type phenylation of aldehydes was developed. The scope, mech-
anism, and synthetic application of this novel reaction are under
investigation.
A typical experimental procedure follows: A mixture of
benzaldehyde (106 mg, 1 mmol), phenyltrimethylstannane (241
mg, 1 mmol), sodium fluoride (210 mg, 5 mmol), and bis(1,4-
cyclooctadiene)rhodium tetrafluoroborate (20 mg, 5% mol) in 20
mL of deionized water was capped and stirred at 110 °C (oil
bath temperature) overnight. Upon cooling, the reaction mixture
was extracted with ethyl acetate. The combined organic fractions
were dried over MgSO4 and concentrated. The residue was
purified by column chromatography on silica gel (eluent: hexane/
ethyl acetate 5:1) to give 151 mg (82% yield) of diphenylmetha-
nol.
Acknowledgment. We are grateful to NSF (CAREER), the NSF-
EPA joint program for a sustainable environment, and LEQSF for partial
support of our research.
Supporting Information Available: Characterization of products
(PDF). This material is available free of charge via the Internet at
http://pubs.acs.org.
(10) Hayashi, T.; Ishigedani, M. J. Am. Chem. Soc. 2000, 122, 976.
JA001699B