withdrawing substituent (i.e., dimethyl fumarate, entry 5)
gave a lower yield of the corresponding addition product
together with substantial amounts of 2-indolecarbaldehyde
2a.
Table 1. Intermolecular Addition Reactions of 2-Indolylacyl
Radicals Derived from Phenyl Selenoesters 1
Clearly the amide carbonyl group does not have enough
electron-withdrawing capacity to guarantee the intermolecular
alkene addition reaction: from 1a and N-tosyl-5,6-dihydro-
2(1H)pyridone8 (entry 6), addition was observed only when
the poorer hydrogen-atom donor tris(trimethylsilyl)silane9
(TTMSS, AIBN, C6H6, 80 °C, slow addition, Method B)10
was used as the radical mediator, although the yield was low.
More satisfactorily, 2-indolylacyl radical derived from 1b
reacted productively with R,â-unsaturated lactam ester 48
under the above Method B conditions (entry 7). Taking into
account that the N-benzyl protecting group can be easily
removed in 2-acylindoles,11 the resulting 2-indolyl 4-piperidyl
ketone 5 can be envisaged as potentially useful for the
synthesis of 2-acylindole alkaloids (e.g., apparicine, dasy-
carpidone).12
When 2-cycloalkenones were used as alkene acceptors
(entries 8 and 9), the use of standard n-Bu3SnH conditions
(Method A) provided a modest yield of the corresponding
adducts. Knowing the ability of TTMSS to reduce ketones,9
the use of nonreductive conditions (n-Bu6Sn2, hν, C6H6, 80
°C, Method C)13 was the most satisfactory solution in these
cases to avoid the competitive reduction of the intermediate
acyl radical. Under these conditions, the corresponding
diketone adducts were isolated in acceptable yield. This result
can be rationalized by considering that the initially formed
R-keto radical A, coming from the addition of the indolylacyl
radical to the enone, reacts with excess n-Bu6Sn2 to give a
tin enolate, which would undergo hydrolysis during the
workup (Scheme 3). The results shown in Table 1 clearly
(6) Selenoesters 1a and 1b were prepared in 60% and 96% yield,
respectively, by reaction of the corresponding carboxylic acid triethylam-
monium salt with PhSeCl and Bu3P in THF at room temperature, following
the procedure reported by the following: Batty, D.; Crich, D. Synthesis
1990, 273-275.
a All compounds were fully characterized by spectroscopic analysis
(NMR) and gave satisfactory HRMS and/or combustion data. b All reactions
were carried out on a 0.6 mmol scale, using a four (or five)-fold excess of
the alkene acceptor. Method A: n-Bu3SnH (1.2 equiv,), AIBN (0.15 equiv),
C6H6, reflux, slow addition. Method B: TTMSS (2 equiv), AIBN (2 equiv),
C6H6, reflux, slow addition. Method C: n-Bu6Sn2 (2 equiv), hν, C6H6,
reflux. c Isolated yields of chromatographically pure material. d Recovering
of 2-indolecarbaldehyde 2a in 60-65%.
(7) General Procedure (Method A): n-Bu3SnH (0.8 mmol) in C6H6
(3 mL) was added over a period of 1 h (syringe pump) to a heated (reflux)
solution of 1a (0.64 mmol), the alkene acceptor (3.2 mmol), and AIBN
(0.1 mmol) in C6H6 (6 mL). After an additional 2-3 h at reflux, the solution
was concentrated under reduced pressure, and the resulting residue was
chromatographed (flash, hexanes-AcOEt).
(8) Casamitjana, N.; Lo´pez, V.; Jorge, A.; Bosch, J.; Molins, E.; Roig,
A. Tetrahedron 2000, 56, 4027-4042.
(9) Chatgilialoglu, C. Acc. Chem. Res. 1992, 25, 188-194.
(10) General Procedure (Method B): TTMSS (1.28 mmol) and AIBN
(1.28 mmol) in C6H6 (4 mL) were added over a period of 2 h (syringe
pump) to a heated (reflux) solution of 1a,b (0.64 mmol) and the alkene
acceptor (3.2 mmol) in C6H6 (12 mL). After an additional 2-3 h at reflux,
the reaction was worked up as in the above Method A.
(11) Watanabe, T.; Kobayashi, A.; Nishiura, M.; Takahashi, H.; Usui,
T.; Kamiyama, I.; Mochizuki, N.; Noritake, K.; Yokoyama, Y.; Murakami,
Y. Chem. Pharm. Bull. 1991, 39, 1152-1156. For synthetic applications,
see ref 4.
(12) (a) Joule, J. A. In Indoles, The Monoterpenoid Indole Alkaloids;
Saxton, J. E., Ed. In The Chemistry of Heterocyclic Compounds; Weiss-
berger, A., Taylor, E. C., Eds.; Wiley: New York, 1983; Vol. 25, Part 4;
Chapter VI. (b) Alvarez, M.; Joule, J. In Monoterpenoid Indole Alkaloids;
Saxton, J. E., Ed. In The Chemistry of Heterocyclic Compounds; Taylor,
E. C., Ed.; Wiley: Chichester, 1994; Vol. 25, Supplement to Part 4; Chapter
6.
(13) General Procedure (Method C): A solution of 1a (0.65 mmol),
cycloalkenone (2.60 mmol) and n-Bu6Sn2 (1.30 mmol) in C6H6 (30 mL)
was refluxed under sun-lamp irradiation (300 W) for 24 h. The reaction
was worked up as in the above Method A.
â-carbon of the alkene component by a methyl group (i.e.,
methyl crotonate, entry 4) did not affect significantly the
effectiveness of the addition, the substitution by an electron-
(1) (a) Curran, D. P. In ComprehensiVe Organic Synthesis; Trost, B. M.,
Fleming, I., Eds.; Pergamon: Oxford, 1991; Vol. 4, pp 715-777 and 779-
831.(b) Giese, B.; Kopping, B.; Go¨bel, T.; Dickhaut, J.; Thoma, G.; Kulicke,
K. J.; Trach, F. Org. React. 1996, 48, 301-856.
(2) (a) Jasperse, C. P. Curran, D. P.; Fevig, T. L. Chem. ReV. 1991, 91,
1237-1286. For representative examples, see: (b) Koert, U. Angew. Chem.,
Int. Ed. Engl. 1996, 35, 405-407.
(3) For a review on the chemistry of acyl radicals, see: Chatgilialoglu,
C.; Crich, D.; Komatsu, M.; Ryu, I. Chem. ReV. 1999, 99, 1991-2069.
(4) (a) Bennasar, M.-L.; Vidal, B.; Bosch, J. J. Org. Chem. 1997, 62,
3597-3609. (b) Bennasar, M.-L.; Vidal, B.; Kumar, R.; La´zaro, A.; Bosch,
J. Eur. J. Org. Chem. 2000, 3919-3925.
(5) (a) Boger, D. L.; Mathvink, R. J. J. Org. Chem. 1989, 54, 1777-
1779. (b) Boger, D. L.; Mathvink, R. J. J. Org. Chem. 1992, 57, 1429-
1443.
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