Angewandte
Chemie
mixture (0.1m) of an aliphatic aldehyde (1a–f) and an
electron-poor olefin (2a–f) in the presence of TBADT (2
10À3 m). To our delight, under these conditions heptaldehyde
1a was found to acylate a,b-unsaturated esters, ketones, and
nitriles (2a–e) in about the same irradiation time (ca. 24 h) to
afford the corresponding functionalized ketones 3–7 in similar
yields of the isolated product (ca. 60% in all cases; see Table 1
and Supporting Information for details).
Thus, the carbonyl hydrogen atom was selectively
abstracted. No reaction took place in the absence of
TBADT, nor were the yields increased by using a larger
amount of TBADT or by adding tert-dodecanthiol (5–
10 mol%) to the reaction mixture.[14]
The scope of the reaction was explored by studying a
primary aldehyde hindered at the b position, namely 3,3-
dimethylbutanal (1b). Acylation of dimethyl maleate took
place in the same irradiation time as with 1a and gave
succinate 8 in a comparable yield. Likewise, the 1,4-diketone
9 was isolated in 60% yield from the photocatalyzed reaction
of a b-phenyl-substituted aldehyde, 3-phenylpropionaldehyde
(1c), with cyclohexenone. On the contrary, acylation was
ineffective when using aromatic aldehydes, as these absorbed
light competitively and were consumed through different
paths, or with electron-rich olefins such as 2,3-dimethylbutene
or cyclohexene (even in the presence of the thiol).
as the sole product (70%). In an attempt to contrast the fast
decarbonylation typical of tertiary acyl radicals,[21] we
repeated the reaction at À508C using the lower melting
propionitrile rather than acetonitrile as solvent. Under these
conditions, compound 14 was again formed as the main
product but was accompanied by ketodiester 15 (16%
yield).[22] Although a reversal of the selectivity was not
obtained in this case,[23] a positive indication about the
thermal control of decarbonylation was obtained; this was,
to our knowledge, the first instance whereby addition of a
tertiary acyl radical onto an alkene was obtained.[24]
In conclusion, the photocatalyzed activation of aldehyde
hydrogen atoms offered an easy access to acyl radicals and the
synthesis of unsymmetrical ketones through trapping by
electrophilic olefins. The method involves the use of
TBADT in a low amount (2 mol%) and equimolar amounts
of the reagents, does not require the use of foul-smelling
auxiliaries, and qualifies as a “green” synthetic method. With
tertiary aldehydes, a single process occurs, namely alkylation.
As with other radical methods, decarbonylation and acylation
processes compete when using secondary aldehydes at room
temperature. However, photocatalysis is equally effective at a
low temperature and allows acylation at À208C with secon-
dary aldehydes and a significant fraction of acylation with
tertiary aldehydes.
An important issue in determining the scope of the
reaction was the decarbonylation of acyl radicals. The
literature shows that this process depends on the stability of Experimental Section
Typical procedure for the photochemical acylation of olefins: A
the corresponding alkyl radicals, on the temperature, and on
the solvent used.[1,15,16] Decarbonylation is known to be
decreased to some extent when using (Me3Si)3SiH/Et3B as
radical initiators[17] and more effectively through an indirect
approach recently proposed by Skrydstrup and co-workers
through SmI2 reduction of different radical precursors (N-acyl
oxazolidinones) at temperatures below À408C.[18] In princi-
ple, the simple approach of lowering the temperature is suited
to aldehydes owing to the lower activation energy of acylation
versus the decarbonylation reaction.[19] However, lowering
the temperature is not an option thermally because it slowed
down the rate of the chain reaction. In the present case, the
photocatalyzed hydrogen-abstraction step was virtually inde-
pendent of the temperature and application to easily frag-
menting acyl radicals at a low temperature seemed possible.[20]
We thus examined secondary aldehydes 1d and 1e. As
expected, photolysis of 2-ethylbutyraldehyde (1d) in the
presence of 2a gave a mixture of acylsuccinate 10 (15%) and
alkylsuccinate 11 (34%, see Table 1). At À208C, however,
ketone 10 was by far the main product (40%) along with a
small amount of 11 (ca. 5%). Likewise, the photocatalyzed
reaction between aldehyde 1e and cyclopentenone (2 f) at
room temperature gave both 1,3-diketone 12 (45%) and 3-
cyclohexylcyclopentanone 13 (25%), whereas at À208C
compound 12 was formed almost exclusively (46%, with
less than 1% 13). Prolonged irradiation led to significant
consumption of both photoproducts.
solution of aldehyde (1a–f, 3 mmol, 0.1m), olefin (2a–f, 0.1m), and
TBADT[11b] (200 mg; 2 10À3 m) in MeCN (30 mL) was poured into
two quartz tubes and purged for 10 min with argon. The tubes were
then serum-capped and irradiated with six 15-W phosphor-coated
lamps (emission centered at 310 nm). The photolyzed solution was
concentrated under reduced pressure, and the products were purified
by bulb-to-bulb distillation. When mixtures were formed, separation
was carried out by column chromatography (on silica gel, with
cyclohexane/ethyl acetate as eluants).
Received: November 28, 2006
Published online: February 26, 2007
Keywords: acylation · aldehydes · alkenes · photochemistry ·
.
radical reactions
[1] C. Chatgilialoglu, D. Crich, M. Komatsu, I. Ryu, Chem. Rev.
1999, 99, 1991 – 2069, and references therein.
[2] a) I. Ryu, N. Sonoda, Angew. Chem. 1996, 108, 1140 – 1157;
Angew. Chem. Int. Ed. Engl. 1996, 35, 1050 – 1066; b) I. Ryu,
Chem. Soc. Rev. 2001, 30, 16 – 25; c) Y. Uenoyama, T. Fukuyama,
I. Ryu, Synlett 2006, 2342 – 2344.
[3] a) S. Bath, N. M. Laso, H. Lopez-Ruiz, B. Quiclet-Sire, S. M.
Zard, Chem. Commun. 2003, 204 – 205; b) R. Braslau, M. O.
Anderson, F. Rivera, A. Jimenez, T. Haddad, J. R. Axon,
Tetrahedron 2002, 58, 5513 – 5523; c) L. Benati, G. Calestani,
R. Leardini, M. Minozzi, D. Nanni, P. Spagnolo, S. Strazzari, Org.
Lett. 2003, 5, 1313 – 1316.
Finally, the photolysis of an equimolar mixture of the
tertiary aldehyde pivalaldehyde (1 f) and maleate 2a in the
presence of TBADT was studied. At room temperature, no
acylation was observed and tert-butylsuccinate 14 was formed
[4] M. S. Kharasch, W. H. Urry, B. M. Kuderna, J. Org. Chem. 1949,
14, 248 – 253.
[5] See, for example: a) H.-S. Dang, B. P. Roberts, J. Chem. Soc.
Perkin Trans. 1 1998, 67– 76; b) K. Yoshikai, T. Hayama, K.
Angew. Chem. Int. Ed. 2007, 46, 2531 –2534
ꢀ 2007 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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