Angewandte
Chemie
results are summarized in Table 1. It can be seen that
prenylation is readily accomplished with phosphine oxide
17, whereas allyl and homoallyl acetates can be introduced
with the corresponding phosphine oxides 19, 25, and 30. The
dithiocarbonate moiety itself can bear a number of useful
functional groups. Besides the initial phenacyl derivative 9,
substrates can contain a lactone (as in 21), a protected
aldehyde ester (as in 23), or, perhaps most interestingly, a
masked a-aminoketone (as in 27; Phth = phthalimido). a-
Aminoketones are at the centre of several classical syntheses
point, access to numerous substituted allyl diphenylphosphine
oxides can be accomplished by direct reaction of the anion
derived from the simplest member 10 with various electro-
philes (alkylating agents, epoxides, aldehydes, and so
forth).[20] Another powerful route is through the Arbuzov–
Tripett rearrangement starting from allylic alcohols.[21] The
radical reaction itself is flexible, convergent, and takes place
under mild neutral conditions.
of heteroaromatic rings, such as pyrroles and pyridines, and Experimental Section
Typical procedure for the radical allylation: Di-tert-butyl peroxide (a
are not always readily accessible. Moreover, the introduction
of many of these allylic fragments would not be trivial by the
more common ionic processes, especially with the more
functionalized substrates.
few drops, ca. 100 mg) was added to a solution of the dithiocarbonate
(1.0 mmol) and allyl phosphine oxide (2.0 mmol) in refluxing
degassed chlorobenzene (10 mL) in a nitrogen atmosphere. A few
more drops (ca. 100 mg) of di-tert-butyl peroxide were added after 4 h
at reflux if the reaction is not yet complete (tlc). The reaction mixture
was then cooled to room temperature, concentrated in vacuo, and
purified by flash chromatography.
Our initial attempt to extend this approach to the
À
formation of C C bonds at the anomeric position of
carbohydrates, such in the 2-deoxyglucose derivative 33, was
frustrated by the premature elimination of the dithiocarbon-
ate group at the temperature of refluxing chlorobenzene to
Received: April 20, 2006
À
give glucal 34 as the major product (Scheme 4). The C Sbond
Keywords: b-elimination · allylation · dithiocarbonates ·
phosphane oxides · radical reactions
.
[1] a) J. Grignon, M. Pereyre, J. Organomet. Chem. 1973, 61, C33 –
C35; b) M. Kosugi, K. Kurino, K. Takayama, T. Migita, J.
Organomet. Chem. 1973, 56, C11 – C13.
[2] a) G. E. Keck, J. B. Yates, J. Am. Chem. Soc. 1982, 104, 5829 –
5831; b) G. E. Keck, E. J. Enholm, D. F. Kachensky, Tetrahedron
Lett. 1984, 25, 1867 – 1870; c) G. E. Keck, E. J. Enholm, J. B.
Yates, M. R. Wiley, Tetrahedron 1985, 41, 4079 – 4094; d) G. E.
Keck, D. F. Kachensky, E. J. Enholm, J. Org. Chem. 1985, 50,
4317 – 4325.
[3] J. E. Baldwin, R. M. Adlington, D. J. Birch, J. A. Crawford, J. B.
Sweeney, J. Chem. Soc. Chem. Commun. 1986, 1339 – 1340.
[4] For exceptions, see: a) G. A. Russell, L. L. Herold, J. Org. Chem.
1985, 50, 1037 – 1040; b) T. Migita, K. Nagai, M. Kosugi, Bull.
Chem. Soc. Jpn. 1983, 56, 2480 – 2484; c) H. Fliri, C.-P. Mak, J.
Org. Chem. 1985, 50, 3438 – 3442; d) C. J. Easton, I. M. Scharf-
billig, J. Org. Chem. 1990, 55, 384 – 386; e) Y. Watanabe, T.
Yoneda, T. Okumura, Y. Ueno, T. Toru, Bull. Chem. Soc. Jpn.
1993, 66, 3030 – 3033; f) Y. Yoshida, N. Ono, F. Sato, J. Org.
Chem. 1994, 59, 6153 – 6155; g) I. Ryu, S. Kreimerman, T.
Niguma, S. Minakata, M. Komatsu, Z. Luo, D. P. Curran,
Tetrahedron Lett. 2001, 42, 947 – 950.
[5] M. D. Johnson, Acc. Chem. Res. 1983, 16, 343 – 349.
[6] S.-I. Usugi, H. Yorimitsu, K. Oshima, Tetrahedron Lett. 2001, 42,
4535 – 4538.
[7] C. C. Huval, D. A. Singleton, Tetrahedron Lett. 1993, 34, 3041 –
3042.
[8] a) G. E. Keck, J. H. Byers, J. Org. Chem. 1985, 50, 5442 – 5444;
b) A. Yanagisawa, Y. Noritake, H. Yamamoto, Chem. Lett. 1988,
1899 – 1902; c) P. Breuilles, D. Uguen, Tetrahedron Lett. 1990, 31,
357 – 360.
[9] For emphasis on the problems linked with tin-mediated radical
chemistry, see: P. A. Baguley, J. C. Walton, Angew. Chem. 1998,
110, 3272 – 3283; Angew. Chem. Int. Ed. 1998, 37, 3072 – 3082; for
a review of tin-free allylations using allylsulfones, see: F.
Bertrand, F. Le Guyader, L. Liguori, G. Ouvry, B. Quiclet-Sire,
S. Seguin, S. Z. Zard, C. R. Acad. Sci. Ser. II 2001, 4, 547 – 555.
[10] One notable exception is the elegant use of a branched
allylsulfone in the total synthesis of (+)-pseudomonic acid C;
Scheme 4. Two special cases. Ts=p-toluenesulfonyl.
is weakened by an anomeric effect of the lone pair of
electrons on the oxygen atom and thus introduces an element
of fragility into the substrate. This complication could be
circumvented in a large measure by reverting to the lower-
boiling 1,2-dichloroethane as the reaction solvent. In this
unprecedented anomeric prenylation of a carbohydrate, the
phosphine oxide is tertiary and therefore the addition–
fragmentation occurs readily at 808C.
A preliminary reaction that involved a simple secondary
dithiocarbonate moiety gave rather disappointing results.
Thus, the attempted allylation of dithiocarbonate 36 gave
mostly reduced piperidine 37 and only a low yield of the
normal product 38. Hydrogen abstraction could take place
from the solvent or from the benzylic position of the
phosphine oxide reagent 30. Further studies are needed to
ascertain the source of the hydrogen atom.
These preliminary results represent a promising approach
to a generalized allylation process and highlight the impor-
tance of the substitution around the phosphorus center in
determining its leaving-group ability. From a synthetic stand-
Angew. Chem. Int. Ed. 2006, 45, 5002 –5006
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