Preparation and reactions of functionalized magnesium carbenoids

Article abstract of DOI:10.1055/s-1999-2935

New functionalized magnesium carbenoids bearing an ester function have been prepared via an iodine-magnesium exchange reaction. These new carbenoids react with various electrophiles (60-88% yield). A substituted magnesium carbenoid has been prepared by su

Full text of DOI:10.1055/s-1999-2935

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LETTER
Preparation and Reactions of Functionalized Magnesium Carbenoids
Salvatore Avolio,a Christophe Malan, Ilan Marek,b Paul Knochela,*
aInstitut für Organische Chemie der Ludwig-Maximilians-Universität, Butenandtstraße 5-13, D-81377 München, Germany
Fax int.+89-2180-7680; E-mail: paul.knochel@cup.uni-muenchen.de
bDepartment of Chemistry, Technion Institute of Technology, Technion City, 32000 Haifa, Israel
Received 2 August 1999
Abstract: New functionalized magnesium carbenoids bearing an
ester function have been prepared via an iodine-magnesium ex-
change reaction. These new carbenoids react with various electro-
philes (60-88% yield). A substituted magnesium carbenoid has been
prepared by sulfoxide-magnesium exchange.
Key words: carbenoids, Grignard reactions, sulfoxides, iodine-
magnesium exchange, polyfunctional organometallics
The preparation of reactive polyfunctional organometal-
lics is an active field of research. Whereas organolithiums
preclude the presence of many functional groups due to
the high reactivity of the carbon-lithium bond, we have re-
cently found that a range of functionalized aryl-,1 alkenyl-
2 and heteroaryl-3 magnesium derivatives can be prepared
by a low temperature iodine-magnesium exchange reac-
tion. Herein, we wish to describe the application of this re-
action in the preparation of magnesium carbenoids of type
1 bearing an ester function. Whereas lithium carbenoids
are highly unstable intermediates,4 magnesium
carbenoids5 are less prone to decomposition and they are
therefore better suited for synthetic applications. So far,
no functionalized magnesium carbenoids have been re-
ported. However, their preparation would expand the ap-
plication field of these reactive reagents. We found that
the treatment of readily available iodomethyl
carboxylates6 of type 2 with i-PrMgCl in THF:N-bu-
tylpyrrolidinone (NBP)7 (5:1) at -78 oC affords, within 15
min, the corresponding magnesium carbenoid of type 1.
These carbenoids which are only stable for a few hours at
–78 °C, react with various electrophiles (aldehyde, ke-
tone, chlorophosphine, immonium salt or allylic halide)
leading to the expected polyfunctional products of type 3
in 60–88% yield (Scheme 1 and Table 1).
Aliphatic or aromatic aldehydes react well with the mag-
nesium reagents 1a-b furnishing the selectively protected
1,2-diols 3a-e. Thus, the reaction of PhCHO with 1a (-78
oC, 15 min, then 12 h at r.t.) in the presence of TMSCl (2.4
Scheme 1
equiv)
furnishes
the
benzylic
alcohol
PivOCH2CH(OH)Ph (3a) in 82% isolated yield (entry 1 of
Synlett 1999, No. 11, 1820–1822 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Preparation and Reactions of Functionalized Magnesium Carbenoids
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Table 1). In the absence of TMSCl, a mixture of 3a and
the acyl-migrated primary alcohol PivOCH(Ph)CH2OH
(4) is obtained. After a reaction time of 14 h, the alcohol
4 is isolated in 73% yield. The reaction of 1a with cyclo-
hexanone furnishes the tertiary alcohol 3f in 88% yield
(entry 6). As expected, diphenyl disulfide reacts with 1a-
b leading to the corresponding mixed thioacetals 3g-h
(entries 7 and 8). The readily prepared immonium salt8
+
-
CH2=N(allyl)2 CF3CO2 reacts smoothly with the magne-
sium reagents 1a-b providing the selectively protected
1,2-amino-alcohols 3i-j in 74-82% yield. The phosphory-
lation of 1a with ClPPh2 gives the phosphine 3k in 75%
yield. The allylation of 1a with ethyl (2-bromometh-
yl)acrylate9 provides the expected allylated compound 3l
in 80% yield (entry 12). It was possible for the first time
to prepare a magnesium bis-carbenoid (6). Thus, treat-
ment of the readily available chiral diiodide 56b with i-
PrMgCl (2.1 equiv, THF:NBP, -78 °C, 15 min) followed
by the addition of PhSSPh (1.8 equiv) led to the desired
bis-coupling product 7 in 70% yield (Scheme 2).
Scheme 3
In summary, we have developed a new preparation of
magnesium carbenoids using either an iodine/magnesium
or a sulfoxide/magnesium exchange reaction. The study
of the scope of this reaction is currently examined in our
laboratories.12
Acknowledgement
We thank the DFG (Leibniz program) and the German-Israelian
Foundation for the financial support of this work. We thank Cheme-
tall (Frankfurt), BASF (Ludwigshafen) and Degussa-Hüls (Hanau)
for the generous gift of chemicals.
References and Notes
(1) Boymond, L.; Rottländer, M.; Cahiez, G.; Knochel, P. Angew.
Chem. Int. Ed. 1998, 37, 1701.
(2) Rottländer, M.; Boymond, L.; Cahiez, G.; Knochel, P. J. Org.
Chem. 1999, 64, 1080.
(3) Bérillon, L.; Leprêtre, A.; Turck, A.; Plé, N.; Quéguiner, G.;
Cahiez, G.; Knochel, P. Synlett 1998, 1359.
Scheme 2
(4) a) Müller, A.; Marsch, M.; Harms, K.; Lorenz, J. C. W.;
Boche, G. Angew. Chem. Int. Ed. Engl. 1996, 35, 1518;
b) Hoffman, R. W.; Julius, M.; Chemla, F.; Ruhland, T.;
Frenzen, G. Tetrahedron 1994, 50, 6049.
(5) a) Villiéras, J. Bull. Soc. Chim. Fr. 1967, 1511; b) Villiéras, J.;
Kirschleger, B.; Tarhouni, R.; Rambaud, M. Bull. Soc. Chim.
Fr. 1986, 470.
(6) a) Knochel, P.; Chou, T.; Jubert, C.; Rajagopal, D. J. Org.
Chem. 1993, 58, 588; b) Binderup, E.; Hansen, E. T. Synth.
Commun. 1984, 14, 857.
(7) N-Butylpyrrolidinone contrary to NMP solubilizes
magnesium reagents at low temperature and proves to be an
excellent cosolvent for this reaction.
In order to extend the scope of this reaction, we have ex-
amined the preparation of substituted functionalized mag-
nesium carbenoids of the type PivOCH(R)MgCl.
However as the preparation of the halogen precursors
(PivOCH(R)X; X=Br, I) proved to be difficult, we further
examined the use of sulfoxides of type 8. According to Sa-
toh,10 sulfoxides may undergo a sulfoxide/Mg exchange
through treatment with a magnesium reagent. The chlori-
nation of ethyl phenyl sulfide 9 (NCS, CH2Cl2, r.t., 2 h)
furnishes the sensitive chloro sulfide 10, which reacts
with pivalic acid (DBU (1 equiv), toluene, 10 h), giving a
mixed thioacetal (78% yield). This was oxidized with
(8) Millot, N.; Avolio, S.; Piazza, C.; Knochel, P. manuscript in
preparation.
o
MCPBA (1 equiv, CH2Cl2, -30 C, 0.5 h) providing the
(9) Villiéras, J.; Rambaud, M. Synthesis 1982, 924.
(10) a) Satoh, T.; Takano, K.; Ota, H.; Someya, H.; Matsuda, K.;
Koyama, M. Tetrahedron 1998, 54, 5557; b) Hoffmann, R.
W.; Nell, P. G. Angew. Chem. Int. Ed. 1999, 38, 338.
(11) The relative configuration of compound 11 has been assigned,
after cleavage of the pivaloyl group, by comparison of the
obtained 1H-NMR spectrum with the spectral data from the
literature: 1H-NMR (300 MHz, CDCl3): d (CH3)threo 1.05 ppm,
3J = 6.3 Hz; d (CH3)erythro 0.89 ppm, 3J = 6.3 Hz); a) Jackson,
W. R.; Jacobs, H. A.; Jayatilake, G. S.; Matthews, B. R.;
Watson, K. G. Aust. J. Chem., 1990, 43, 2045; b) Nakajima,
M.; Tomioka, K.; Iitaka, Y.; Koga, K. Tetrahedron 1993, 47,
10793.
sulfoxide 8. We were pleased to find that 8 in presence of
i-PrMgBr (THF, -78 oC, 15 min) undergoes a fast Mg/sul-
foxide exchange, leading to the desired magnesium car-
benoid 1c which by reaction with PhCHO (0.8 equiv) and
TMSCl (2.4 equiv) affords selectively protected 1,2-diol
derivative 11 (erythro:threo = 7:93)11 in 61% yield
(Scheme 3).
Synlett 1999, No. 11, 1820–1822 ISSN 0936-5214 © Thieme Stuttgart · New York

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S. Avolio et al.
LETTER
Typical procedure: Preparation of 2-hydroxy-2-phenylethyl
pivalate (3a; entry 1 of Table 1). A 50 mL Schlenk-flask was
charged with i-PrMgCl (5.5 mL, 3.3 mmol) and was cooled to
-78 oC. A solution of iodomethyl pivalate (2a, 726 mg, 3
mmol) in 5 mL of a 5:1 THF:NBP mixture was added
typical workup, the crude residue obtained after evaporation
of the solvent was purified by flash-chromatography
(pentane:ether = 7:3) affording the desired product 3a as a
colourless oil (547 mg, 82% yield).
dropwise over 10 min. After further 10 min at -78 oC, PhCHO
(255 mg, 2.4 mmol) was added together with TMSCl (782 mg,
7.2 mmol) in THF (2 mL). The reaction mixture was allowed
to warm to r.t. over 3 h and was further stirred for 8 h. After a
Article Identifier:
1437-2096,E;1999,0,11,1820,1822,ftx,en;G20399ST.pdf
Synlett 1999, No. 11, 1820–1822 ISSN 0936-5214 © Thieme Stuttgart · New York