Synthesis of natural quinazolinones and some of their analogues through radical cascade reactions involving N-acylcyanamides

Article abstract of DOI:10.1016/j.tet.2013.05.058

Two natural quinazolinones and two analogues can be prepared from the cascade cyclizations of alkyl-substituted N-acylcyanamide radicals, including 5-exo-dig or 6-exo-dig cyclizations onto the cyano group, followed by radical arylations of the resulting amidyl radicals. The fact that one can carry out the cascades from alkyl radicals in addition to aryl, vinyl and aminyl ones, shows the versatility of the method to rapidly access nitrogen-containing polycyclic structures.

Full text of DOI:10.1016/j.tet.2013.05.058

Tetrahedron 69 (2013) 7699e7705
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Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Synthesis of natural quinazolinones and some of their analogues
through radical cascade reactions involving N-acylcyanamides
a
a
a
a,
*
,
ꢀ ꢁ
Marie-Helene Larraufie , Max Malacria , Christine Courillon , Cyril Ollivier
Louis Fensterbank a , Emmanuel Lacote
UPMC Sorbonne Universites, Institut Parisien de Chimie Moleculaire, UMR CNRS 7201, 4 place Jussieu, 75005 Paris, France
,
a,b,
*
*
^
a
ꢀ
ꢀ
b
ꢀ
ꢀ
Universite de Lyon, Institut de chimie de Lyon, UMR 5265 CNRS-Universite Lyon I-ESCPE Lyon, 43 Bd du 11 novembre 1918, 69616 Villeurbanne, France
a r t i c l e i n f o
a b s t r a c t
Article history:
Two natural quinazolinones and two analogues can be prepared from the cascade cyclizations of alkyl-
substituted N-acylcyanamide radicals, including 5-exo-dig or 6-exo-dig cyclizations onto the cyano group,
followed by radical arylations of the resulting amidyl radicals. The fact that one can carry out the cas-
cades from alkyl radicals in addition to aryl, vinyl and aminyl ones, shows the versatility of the method to
rapidly access nitrogen-containing polycyclic structures.
Received 13 March 2013
Received in revised form 14 May 2013
Accepted 16 May 2013
Available online 28 May 2013
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Radical reactions
Cyanamides
Quinazolinones
1. Introduction
the intermediate cyclohexadienyl radical.3b We could also devise
a very versatile route to guanidines using an aminyl radical to ini-
One of the great features of radical processes is that they allow
the rapid increase of molecular complexity in one controlled op-
eration. This is achieved via the stepwise formation of bonds in
programmed substrates and obeys the principles of atom economy
and step economy. Thus, radical cascades have been applied in
various contexts,1 and they are at the root of valuable strategies for
the total synthesis of natural products.2 Despite a broad spectrum
of existing functional partners amenable to the design of cascades,
there remains however a need for new building blocks and func-
tions to be added to the palette.
Recently, we have been interested in the use of N-acylcyana-
mides as relay partners in radical cascades.3 The principle of this
approach relies on the fact that this function can have a dual role as
radical acceptor (addition of Rꢀ) on the carbon atom of the NeCN
groupand that the resulting amideeiminyl radical can be engaged in
a cyclization as well. This allowed us to discover an intriguing radical
cascade initiated by vinyl radicals (Scheme 1a). It featured a homo-
lytic aromatic substitution step followed by the formal addition on
the vinyl moiety of the radicals generated by the rearomatization of
tiate the cascade (Scheme 1b).3c
N
R
N
R
N
N
amide-iminyl radical
O
N
CF3
(a)
CF3
O
I
Bu3SnH
AIBN
N
N
N
t-BuOH, Δ
55%
F3C
CF3
O
(b)
(c)
O
Bu3SnH
AIBN
N
N
N3
PhH, Δ
76%
N
H
N
N
O
N
O
N
air, pyr.
N
PhH, hν
* Corresponding authors. Tel.: þ33 1 44 27 38 47; fax: þ33 1 44 27 73 60 (C.O.);
tel.: þ33 1 44 27 38 47; fax: þ33 1 44 27 73 60 (L.F.); tel: þ33 4 72 44 82 46; fax:
þ33 4 72 43 17 68 (E.L.); e-mail addresses: cyril.ollivier@upmc.fr (C. Ollivier),
louis.fensterbank@upmc.fr (L. Fensterbank), emmanuel.lacote@univ-lyon1.fr (E.
N
I
N
N
54%
Luotonin A
Scheme 1. Radical cascades involving N-acylcyanamides.
^
Lacote).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.05.058

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M.-H. Larraufie et al. / Tetrahedron 69 (2013) 7699e7705
The cascades proved useful in a total synthesis context. Starting
with an initially formed 2-quinolyl radical the serial cyclization
process provided Luotonin A (Scheme 1c).3a Herein, we broaden
the cascade scope to the synthesis of additional natural products,
as well as some of their analogues, using alkyl radicals as triggers.
O
N
O
N
N
N
n
n
R1
R2
X
R1
R2
A
R1, R2 = H, Me
n = 1, 2
2. Results and discussion
2.1. Synthetic targets
O
NH2
N
n
n
R1
R2
H
R1
R2
X
X
Four synthetic targets were defined. Two of them were natural
quinazolinones (Fig. 1).
C
B
Scheme 2. Retrosynthetic analysis for the preparation of the target compounds.
O
N
O
N
N
3-bromopropylamine (5) led to only 28% of the desired amide 6.
The major product 7 resulted from an intramolecular O-alkylation
side-reaction (Scheme 3).
N
Deoxyvasicinone 1
Mackinazolinone 2
O
N
O
O
N
Br
N
H
Ph
N
N
PhCOCl
Et3N
6, 28%
α-Methyldeoxyvasicinone 3
α,α'-Dimethyldeoxyvasicinone 4
Br
NH2 .HBr
+
CH2Cl2, rt
Fig. 1. Quinazolinones synthetic targets.
5
N
O
Ph
Deoxyvasicinone 1 is a natural alkaloid, which was isolated in
1957 from the leaves of Adhatoda vasica.4 This compound possesses
anti-depressive, antibacterial and anti-inflammatory properties.5
Various methodologies have been developed for its synthesis,
such as a Pd-catalyzed carbonylation/cyclization tandem reaction,6
a transition metal complex-catalyzed reductive N-heterocycliza-
tion7 or a tandem intramolecular Staudinger/aza-Wittig reaction.8
In 2007, Bowman reported the first radical synthesis of deoxy-
vasicinone. It used an alkyl radical generated by treatment of the
corresponding alkyl iodide with BEt3 and O2 and its oxidative cy-
clization on the 3H-quinazolin-4-one core.9
Mackinazolinone 2 is another natural quinazolinone. It is fused
with a piperidine ring and can be viewed as the 1C homologue of 1.
This compound was isolated in 1965 in New Guinea from the leaves
of Mackinlaya subulata10 and has also shown a large spectra of
pharmaceutical activities.11 Numerous synthetic methodologies
similar to those developed for deoxyvasicinone have been applied
to the construction of mackinazolinone 2.8,9
7, 50%
Scheme 3. Attempt for direct benzoylation of bromoamine 5.
We thus replaced the bromine with a phenylselenyl group,
which is cleaved by tin radicals as quickly as bromine atoms,14 but is
a poor nucleofuge (Scheme 4). Accordingly, 3-bromoammoniums 5
and 8 were converted to their seleno derivatives 9a and 9b by
nucleophilic substitutions with sodium phenylselenoate (obtained
by reduction of diphenyldiselenide).15 Compound 8 was obtained
by bromination of commercial 4-amino-butan-1-ol.16 Seleno-
amines 9a and 9b were benzoylated, affording the corresponding
selenoamides 10a and 10b in 89% and 69% yields, respectively.
Cyanation of 10a,b was first carried out with 3 equiv of BrCN and
a
-Methyldeoxyvasicinone 3 is an unnatural analogue of deox-
HBr
NH2
yvasicinone 1 presenting a bronchodilator activity.12
Br
NH3+, Br–
HO
n
H2O,
Δ
Six syntheses of 3 have been reported,13 but none of them in-
cluded a radical step. To the best of our knowledge, the quaternary
analogue of
described.
Our general synthetic strategy is outlined in Scheme 2, which
relies on a radical cascade involving N-acylcyanamides. Thus, the
appropriate substrates with alkyl radical precursors (A) might be
prepared from benzamides B and finally amines C, i.e., the cyana-
tion is envisaged as the last step. The order for the two steps can be
reversed.
5, n = 1 (commercial)
8, n = 2, quant.
a,a 4 has never been
0-dimethyldeoxyvasicinone
PhSeSePh
NaBH4
PhCOCl
Et3N
PhSe
NH2
CH2Cl2, rt
n
EtOH, rt
9a, n = 1, 89%
9b, n = 2, 69%
O
O
N
1. KH
2. BrCN
N
N
Ph
PhSe
Ph
PhSe
n
n
H
THF, rt
2.2. Synthesis of cascade precursors
10a, n = 1, 78%
10b, n = 2, 82%
11a, n = 1, 87%
11b, n = 2, 85%
2.2.1. Preparation of the substrates for the synthesis of deoxy-
vasicinone (1) and mackinazolinone (2). Our initial plan was to
use a bromide as radical source. However, the benzoylation of
Scheme 4. Synthesis of the substrates for the synthesis of 1 and 2.

M.-H. Larraufie et al. / Tetrahedron 69 (2013) 7699e7705
7701
1 equiv of sodium hydride.3a However, the yields were low (about
O
20%). The replacement of sodium hydride with potassium hydride
to generate more nucleophilic amidyl anions led to the desired N-
acylcyanamides 11a and 11b in much better yields (87% and 85%,
Scheme 4).
O
N
K
O
HBr
Br
N
DMF, 80 °C
AcOH
O
18, 74%
2.2.2. Preparation of the substrate for the synthesis of
a-methyl-
O
O
deoxyvasicinone (3). The N-acylcyanamide substrate for the cas-
cade leading to 3 was obtained in six steps from commercially
available 1,3-dichlorobutane (Scheme 5). The latter was selectively
mono-iodinated to afford 3-chloro-1-iodobutane 12, which was
reacted with potassium phthalimide to provide 13. Selenylation of
the secondary chloride was achieved by treatment with the in situ
generated sodium phenylselenoate to give 14, which was directly
deprotected with hydrazine to afford selenoamine 15 in 51% yield
over two steps. Amine 15 was cyanated first to 16 according to
Harrison’s methodology,17 then acylated to obtain the desired N-
acylcyanamide 17 in 90% yield.
In
PhSe
(PhSe)2
Br
N
N
CH2Cl2, Δ
O
O
19, 93%
20, 63%
Ph
Cl
, Et3N
H2N–NH2•H2O
EtOH, Δ
PhSe
O
NH2
CH2Cl2, rt
21, 81%
N
KH
BrCN
H
N
PhSe
N
PhSe
THF, rt
O
O
O
N
K
23, 60%
22, 49%
Cl
NaI
Cl
O
Scheme 6. Synthesis of the precursor of a,a
0-dimethyldeoxyvasicinone (23).
acetone, rt
DMF, 80 °C
Cl
N
I
12, 65%
Cl
O
SePh
O
was easily purified owing to its high polarity. Noticeably, the tin
byproduct Bu3SnSePh formed during the reaction is apolar and
stable on silica gel, which contributes to its easy removal, as op-
posed to that of halogeno-stannanes. Thus, it was first eliminated
by washing the column with pentane. Then elution with polar
solvents allowed the isolation of pure 1 (65% yield). We attempted
to replace the tin-based mediator with (TMS)3SiH,19 but the yield
dropped to only 20%.
PhSeNa
N
DMF, 100 °C
O
O
14
13, 89%
BrCN
Na2CO3
SePh
H2N–NH2•H2O
EtOH, Δ
Et2O, –10 °C
NH2
15, 51% (2 steps)
Bu3SnH, AIBN
O
Ph
Cl
R1 R2
PhSe
slow addition
O
O
SePh
N
SePh
, Et3N
O
(0.2 mmolSnH/h)
N
n
N
N
n
N
N
Ph
N
H
CH2Cl2, rt
PhH, Δ
N
R2
R1
16, 77%
17, 90%
11a: R1 = R2 = H, n = 1
11b: R1 = R2 = H, n = 2
17: R1 = Me, R2 = H, n = 1
23: R1 = R2 = Me, n = 1
O
N
O
N
Scheme 5. Synthesis of the precursor of a-methyldeoxyvasicinone (17).
N
2.2.3. Preparation of the substrate for the synthesis of
a,a
0-dime-
N
1, 65%
O
thyldeoxyvasicinone (4). The N-acylcyanamide substrate for the
cascade leading to 4 was also obtained in six steps, this time
starting from commercially available 3,3-dimethylallyl bromide
(Scheme 6). Potassium phthalimide was allylated by 3,3-
dimethylallyl bromide at 80 ꢁC, leading to phthalimide 18. Hydro-
bromination of the double bond was then performed with an HBr
solution in acetic acid, giving 19. Several conditions were tested for
the nucleophilic substitution on the quaternary carbon of 19 and
the only successful strategy was the Barbier-type indium-mediated
method developed by Jang et al.18 This delivered selenoester 20 in
63% yield. Finally, the phthalimide in 20 was removed using hy-
drazine (yielding 81% of free amine 21). In this case, the amine was
first acylated to 22 (49%), then cyanated to the desired N-acylcya-
namide 23 (60%).
2, 51%
O
N
N
N
N
3, 76%
4, 87%
Scheme 7. Radical cyclization of N-acylcyanamides.
Using the procedure outlined above, substrate 11b delivered
mackinazolinone 2 in 51% yield together with the product of direct
reduction (not isolated). The latter was observed because the initial
6-exo-dig cyclization is much slower than the 5-exo-dig cyclization
leading to 1. This also shows that the cascade can start with a 6-exo-
dig cyclization from an alkyl radical, and not only with a 5-exo-dig
process, or with 6-exo-dig steps from aminyl3c and vinyl radicals.3b
2.3. Radical cyclizations
In a typical cyclization (Scheme 7), Bu3SnH (1.2 equiv) was
slowly added to substrate 11a in the presence of stoichiometric
AIBN (1.5 equiv) in refluxing benzene (0.017 M). Quinazolinone 1
Similarly,
yvasicinone
respectively.
a
4
-methyldeoxyvasicinone 3 and
were obtained in good 76% and 87% yields,
a,a
0-dimethyldeox-

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M.-H. Larraufie et al. / Tetrahedron 69 (2013) 7699e7705
2.4. Mechanistic proposal
in acetone at 0 ꢁC. Thin layer chromatography (TLC) was performed
on Merck 60 F254 silica gel. Merck Geduran SI 60 A silica gel
ꢂ
In the light of our previous mechanistic study,3b we propose the
mechanism depicted in Scheme 8 for the formation of the cascade
adducts. It is illustrated for the cyclization of 11a to 1, but can be
easily extrapolated to the cases of 11b, 17 and 23. Phenylselenide
abstraction by the tributyltin radical leads to the alkyl radical 24ꢀ,
which undergoes a 5-exo-dig cyclization to the cyanamide moiety.
The intermediate amideeiminyl radical 25ꢀ generated can then be
trapped at the ortho position of the benzoyl phenyl ring, leading to
cyclohexadienyl radical 26ꢀ. Consistent with the Beckwith/Storey
rearomatization mechanism, 26ꢀ presumably rearomatized through
bimolecular abstraction of the ipso hydrogen atom by AIBN (formal
addition of Hꢀ to the N]N bond).20 This step generates a new
molecule of quinazolinone and consumes AIBN. The adduct radical
is hydrogenated by Bu3SnH to deliver the reduced AIBN and a new
tin radical. The hydrogenation of AIBN explains why the reaction
only works with a stoichiometric amount of initiator.
(35e70 mm) was used for column chromatography. The melting
points reported were measured with a Reichert hot stage apparatus
and are uncorrected. IR spectra were recorded with a Bruker Tensor
27 ATR diamant PIKE spectrometer. Optical rotations were mea-
sured using a PerkineElmer 341 polarimeter. 1H, 13C and 19F NMR
spectra were recorded at 400, 100 and 377 MHz, respectively, using
a Bruker 400 AVANCE spectrometer fitted with a BBFO probehead.
Chemical shifts are given in parts per million using the CDCl3 or the
MeOD-d4 signal as reference (1H¼7.26 ppm, 13C¼77.16 ppm and
1H¼3.31 ppm, 13C¼49.00 ppm, respectively). Unless noted, NMR
spectra were recorded in CDCl3 at 300 K. The terms m, s, d, t, q,
quint. and sext. represent multiplet, singlet, doublet, triplet, qua-
druplet, quintuplet, and sextuplet, respectively, and the term br
means a broad signal. Exact masses were recorded by Structure et
ꢀ
Function de Molecules Bioactives (UMR 7201) of Universite Pierre
et Marie Curie (electrospray source).
4.2. Preparation and cyclization of alkyl precursors
O
N
O
Bu3SnH, AIBN
4.2.1. General procedures
N
PhSe
N
N
4.2.1.1. General procedure 1 (GP1). 4.2.1.1.1. Conversion of alkyl
bromides into phenylseleno derivatives.15 To a solution of diphe-
nyldiselenide (0.5 equiv) in EtOH (0.02 M) at rt was added NaBH4
(1 equiv). The reaction mixture was stirred at rt during 30 min, then
a solution of the amine bromide hydrobromide (1 equiv) in EtOH
(0.2 M) was added. The reaction mixture was stirred under reflux
during 4 h. Aqueous NaOH 1 M was added and the amine was
extracted two times with CH2Cl2. The combined organic layers were
washed with water, dried over MgSO4 and concentrated in vacuo to
afford the desired phenylseleno derivative as orange oil.
11a
1
H
N
CN
Bu3Sn
+
NC
N
H
Bu3SnSePh
Bu3SnH
H
O
N
N
N
CN
NC
N
24•
5-exo-dig
or
4.2.1.2. General procedure
2 (GP2). 4.2.1.2.1. Preparation of
6-exo-dig
phthalimides. To a solution of halide (1 equiv) in DMF (0.6 M) was
added potassium phthalimide (1.5 equiv). After 3 h at 90 ꢁC, the
mixture was quenched with water. The aqueous layer was then
extracted with Et2O. The organic extracts were combined, dried
over MgSO4 and concentrated under reduced pressure. The residue
was purified by flash column chromatography to afford the desired
phthalimide.
O
N
O
H
H
N
N
H
N
26•
25•
N
CN
NC
Scheme 8. Mechanistic proposal.
N
4.2.1.3. General procedure
3 (GP3). 4.2.1.3.1. Preparation of
amines from phthalimides. To a solution of phthalimide (1 equiv) in
EtOH (0.1 M) was added hydrazine monohydrate (2 equiv). After
refluxing for 2 h, a solution of HCl 6 M was added. The mixture was
filtered and the filtrate was neutralized by a solution of NaOH 2 M.
The aqueous layer was then extracted with Et2O. The organic ex-
tracts were combined, dried over MgSO4 and concentrated under
reduced pressure to afford the desired amine.
3. Conclusion
To conclude, we have shown that natural products can be pre-
pared from N-acylcyanamides using a radical cascade strategy,
which was extended to alkyl radical triggers. A new array of qui-
nazolinones should now be open for testing, using our methodol-
ogy. Future work will seek to extend the cascades using
intermolecular bond forming events. This should side-step the is-
sue of the preparation of the all-intramolecular cascade substrate
and provide a faster access to the molecules.
4.2.1.4. General procedure 4 (GP4). 4.2.1.4.1. Benzoylation of se-
lenoamines. To a solution of selenoamine (1 equiv) in CH2Cl2
(0.1 M) at 0 ꢁC was added NEt3 (2 equiv), and 15 min later, benzoyl
chloride (1.1 equiv). The reaction mixture was stirred at rt during
14 h, then hydrolyzed by a saturated solution of NH4Cl. The aqueous
layer was extracted two times with CH2Cl2. The combined organic
layers were washed with water, dried over MgSO4 and concen-
trated in vacuo. Purification by flash column chromatography
afforded the seleno amide as a white solid.
4. Experimental section
4.1. General remarks
Reactions were carried out under argon, with magnetic
stirring and redistilled solvents. THF and Et2O were distilled from
sodium/benzophenone. CH2Cl2, DMF and NEt3 were distilled from
CaH2. Benzene was distilled from sodium/potassium amalgam. 2,2-
Azobis(2-methylpropionitrile) (AIBN) was purified by precipitation
4.2.1.5. General procedure 5 (GP5). 4.2.1.5.1. Preparation of N-
acylcyanamides. To freshly degreased KH (1.2 equiv) was added
a solution of seleno amide (1 equiv) in THF (0.14 M) at rt. The re-
action mixture was stirred during 45 min, then a solution of BrCN
(3 equiv) in CH2Cl2 (3.0 M) was added. The resulting reaction

M.-H. Larraufie et al. / Tetrahedron 69 (2013) 7699e7705
7703
mixture was stirred at rt during 24 h and filtered through a short
pad of silica. The filtrate was concentrated under reduced pressure
and purified by flash column chromatography to afford the cyan-
amide as a pale yellow oil. Caution: Cyanogen bromide is a very
toxic reagent and must be carefully manipulated under a ventilated
hood. All the glassware must be washed with a NaOH solution
(0.5 M) and bleach (10%).
110 ꢁC, the mixture was quenched with water. The aqueous layer
was then extracted with CH2Cl2 (15 mL). The organic extracts were
combined, dried over MgSO4 and concentrated under reduced
pressure to afford 2-(3-phenylselanyl-butyl)-isoindole-1,3-dione 14
(2.02 g; 67%) as a pale yellow oil. Following GP3 with 14 (4.5 mmol;
1.63 g), 3-phenylselanyl-butylamine 15 (780 mg; 76%) was isolated
as a pale yellow oil. IR (ATR):
1578, 1476, 1436, 1375, 1253, 1066, 1021, 739, 691 cmꢂ1
(400 MHz, CDCl3):
n
¼3295, 3024, 2950, 2917, 2860, 1649,
;
1H NMR
d
¼1.31 (s, 2H, NH2), 1.45 (d, J¼6.8 Hz, 3H, Me),
4.2.1.6. General procedure 6 (GP6). 4.2.1.6.1. Cyclization of N-
1.72e1.84 (m, 2H, NeCH2eCH2), 2.84e2.91 (m, 2H, NeCH2), 3.39
(sextet, J¼6.9 Hz, 1H, SeeCH), 7.25e7.30 (m, 3H, arom.), 7.55e7.57
acylcyanamides. To
a degassed solution of N-acylcyanamide
(1 equiv) and AIBN (0.3 equiv) in benzene (final concentra-
tion¼0.017 M, 75% final volume) under reflux were added Bu3SnH
(2 equiv) and AIBN (1.2 equiv) in benzene (25% final volume) over
2 h (0.2 mmol Bu3SnH/h). The reaction mixture was refluxed for an
additional hour, cooled to rt and concentrated under reduced
pressure. Purification of the residue by flash column chromatog-
raphy afforded the cyclization product.
(m, 2H, arom.). 13C NMR (100 MHz, CDCl3):
d
¼22.6 (CHeMe), 37.2
(SeeCH), 40.6 (NeCH2eCH2), 41.6 (NeCH2), 127.6 (2CH arom.),129.1
(CH arom.), 129.2 (C arom.), 135.2 (2CH arom.); HRMS calcd for
C10H16NSe ([MþH]þ) 230.0442, found 230.0440.
4.2.2.5. 2-(3-Methyl-3-phenylselanyl-butyl)-isoindole-1,3-dione
(20). Following GP2 with 3,3-dimethylallyl bromide (20.0 mmol;
2.66 mL), 18 (petroleum ether/Et2O¼6:2; 3.20 g; 74%) was isolated
as a white solid.22 A solution of 18 (12.5 mmol; 1 equiv; 2.70 g) and
HBr (33% in AcOH, 20 mL) was stirred at rt for 2 h. Water was then
added and the aqueous layer was extracted with Et2O. The organic
extracts were combined, dried over MgSO4 and concentrated under
reduced pressure to afford 19 (3.45 g; 93%) as a white solid. To
a solution of indium (2.7 mmol; 1.3 equiv; 313 mg) and diphe-
nyldiselenide (2.7 mmol; 1.3 equiv; 844 mg) in CH2Cl2 (30 mL), was
added 19 (2.1 mmol; 616 mg). The reaction mixture was refluxed
for 1 h, then hydrolyzed with a 1 M HCl solution. The aqueous layer
was extracted with CH2Cl2. The combined organic layers were
washed with water, dried over MgSO4 and concentrated in vacuo.
Purification by flash column chromatography (petroleum ether/
EtOAc¼10:3) afforded 20 (490 mg; 63%) as a white solid.18 IR (ATR):
4.2.2. Alkyl seleno precursors
4.2.2.1. 3-Phenylselanyl-1-propylamine (9a). Following GP1 with
3-bromopropylamine hydrobromide (7 mmol; 1.53 g), 9a was iso-
lated as an orange oil (1.33 g; 89%). Spectral data are in accordance
with those reported in the literature.16 1H NMR (400 MHz, CDCl3):
d
¼1.46 (br s, 2H, NH2), 1.79e1.86 (m, 2H, PhSeeCH2eCH2), 2.78 (t,
J¼7.2 Hz, 2H, PhSeeCH2), 2.94 (t, J¼7.1 Hz, 2H, NH2eCH2), 7.21e7.26
(m, 3H, arom.), 7.47e7.49 (m, 2H, arom.); 13C NMR (100 MHz, CDCl3):
d
¼25.0 (PhSeeCH2eCH2), 29.7 (PhSeeCH2), 41.6 (NH2eCH2), 126.8
(CH arom.), 129.2 (2CH arom.), 130.2 (C arom.), 132.4 (2CH arom.).
4.2.2.2. 4-Phenylselanyl-butylamine
(9b). 4-Aminobutan-1-ol
(3.9 mmol; 350 mg) was refluxed for 3 h in an aqueous solution of
HBr 48% wt (30 mL). After concentration in vacuo, 4-bromo-
butylamine hydrobromide was obtained as a white solid. Following
GP1 with crude 4-bromobutylamine hydrobromide, 9b was isolated
as an orange oil (606 mg; 69%). Spectral data are in accordance with
n
¼1767, 1705, 1396, 1365, 1331, 1143, 722 cmꢂ1; 1H NMR (400 MHz,
CDCl3):
d
¼1.43 (s, 6H, CMe2), 1.78e1.82 (m, 2H, NeCH2eCH2),
3.93e3.97 (m, 2H, NeCH2), 7.30e7.36 (m, 3H, arom.), 7.68e7.76 (m,
4H, arom.), 7.83e7.85 (m, 2H, arom.); 13C NMR (100 MHz, CDCl3):
those reported in the literature.16 1H NMR (400 MHz, CDCl3):
d¼1.22
d
¼29.9 (CMe2), 35.6 (NeCH2eCH2), 40.9 (CMe2), 44.9 (NeCH2),
(br s, 2H, NH2),1.45e1.49 (m, 2H, PhSeeCH2eCH2),1.62e1.70 (m, 2H,
NH2eCH2eCH2), 2.60 (t, J¼7.0 Hz, 2H, PhSeeCH2), 2.84 (t, J¼7.3 Hz,
2H, NH2eCH2), 7.12e7.18 (m, 3H, arom.), 7.40e7.42 (m, 2H, arom.);
123.3 (2CH arom.), 127.4 (C arom.), 128.8 (3CH arom.), 132.3 (2C
arom.), 134.0 (2CH arom.), 138.5 (2CH arom.), 168.3 (2CO); HRMS
calcd for C19H19NO2SeNa ([MþNa]þ) 396.0473, found 396.0470.
13C NMR (100 MHz, CDCl3):
CH2eCH2), 33.6 (PhSeeCH2), 41.4 (NH2eCH2),126.5 (CH arom.),128.8
d
¼27.3, 27.5 (PhSeeCH2eCH2þNH2e
4.2.2.6. 3-Methyl-3-phenylselanyl-butylamine (21). Following
GP3 with 20 (1.05 mmol; 390 mg), 3-methyl-3-phenylselanyl-
butylamine 21 (205 mg; 81%) was isolated as a yellow oil. IR (ATR):
(2CH arom.), 130.3 (C arom.), 132.2 (2CH arom.).
n
¼2922, 1577, 1465, 1435, 1364, 1121, 1022, 1000, 739, 693 cmꢂ1; 1H
4.2.2.3. 2-(3-Chloro-butyl)-isoindole-1,3-dione (13). To a solu-
tion of sodium iodide (60 mmol; 1 equiv; 8.99 g) in acetone (20 mL)
was added 1,3-dichlorobutane (60 mmol; 1 equiv; 6.83 mL). The
reaction mixture was stirred for 2 h at rt and filtrated. The filtrate
was concentrated under reduced pressure and Et2O (30 mL) was
added to precipitate inorganic salts. After a second filtration, the
filtrate was concentrated under pressure to afford 3-chloro-1-
iodobutane (8.50 g; 65%) as a yellow oil.21 Following GP2 with the
latter (8.72 mmol,1.90 g), 2-(3-chloro-butyl)-isoindole-1,3-dione 13
(petroleum ether/Et2O¼10:1; 1.84 g; 89%) was isolated as a white
NMR (400 MHz, CDCl3):
d
¼1.37 (s, 6H, CMe2), 1.42 (s, 2H, NH2),
1.68e1.72 (m, 2H, NeCH2eCH2), 2.89 (t, J¼8.0 Hz, 2H, NeCH2),
7.28e7.32 (m, 2H, arom.), 7.34e7.37 (m, 1H, arom.), 7.61e7.63 (m,
2H, arom.). 13C NMR (100 MHz, CDCl3):
d
¼30.2 (CMe2), 39.2
(NeCH2eCH2), 46.0 (CMe2), 47.5 (NeCH2), 127.8 (C arom.), 128.7
(2CH arom.), 128.8 (CH arom.), 138.3 (2CH arom.); HRMS calcd for
C11H18NSe ([MþH]þ) 244.0599, found 244.0595.
4.2.2.7. N-(3-Phenylselanyl-propyl)-benzamide (10a). Following
GP4 with 9a (7.47 mmol; 1.60 g), 10a was purified by flash column
chromatography (petroleum ether/EtOAc¼8:2) and isolated as
a white solid (1.85 g; 78%). Spectral data are in accordance with
those reported in the literature.23 1H NMR (400 MHz, MeOD):
solid. IR (ATR):
n
¼2922, 1764, 1698, 1494, 1443, 1401, 1380, 1290,
1085, 959, 712 cmꢂ1; 1H NMR (400 MHz, CDCl3):
d
¼1.55 (d, J¼6.6 Hz,
3H, Me), 2.02e2.12 (m, 2H, NeCH2eCH2), 3.77e3.91 (m, 2H,
NeCH2), 3.99e4.08 (m, 1H, MeCH), 7.69e7.71 (m, 2H, arom.),
7.81e7.84 (m, 2H, arom.); 13C NMR (100 MHz, CDCl3):
d¼25.4 (Me),
d
¼1.95e2.00 (m, 2H, PhSeeCH2eCH2), 2.97 (t, J¼7.2 Hz, 2H,
35.8 (NeCH2eCH2), 38.8 (NeCH2), 55.7 (MeCH), 123.4 (2CH arom.),
132.2 (2C arom.), 134.1 (2CH arom.), 168.3 (2CO); HRMS calcd for
C12H12NO2ClNa ([MþNa]þ) 260.0449, found 260.0449.
PhSeeCH2), 3.47 (t, J¼7.0 Hz, 2H, NHeCH2), 7.22e7.26 (m, 3H,
arom.), 7.42e7.47 (m, 2H, arom.), 7.49e7.57 (m, 3H, arom.),
7.78e7.80 (m, 2H, arom.), NH is missing; 13C NMR (100 MHz,
MeOD):
d
¼25.6 (PhSeeCH2eCH2), 31.2 (PhSeeCH2), 40.9
4.2.2.4. 3-Phenylselanyl-butylamine (15). To a solution of so-
dium phenylselenolate (8.4 mmol; 1 equiv; 1.50 g) in DMF (8 mL)
was added chloride 13 (8.4 mmol; 1 equiv; 2.00 g). After 14 h at
(NHeCH2), 127.9 (CH arom.), 128.3 (2CH arom.), 129.6 (2CH arom.),
130.2 (2CH arom.), 131.5 (C arom.), 132.6 (CH arom.), 133.7 (2CH
arom.), 135.7 (C arom.), 170.3 (CO).

7704
M.-H. Larraufie et al. / Tetrahedron 69 (2013) 7699e7705
4.2.2.8. N-(4-Phenylselanyl-butyl)-benzamide (10b). Following
pressure and purified by flash column chromatography (petroleum
ether/Et2O¼10:2), to afford N-acylcyanamide 17 as a white solid
GP4 with 9b (1.07 mmol; 244 mg),10b was purified by flash column
chromatography (petroleum ether/EtOAc¼5:1) and isolated as
a white solid (290 mg; 82%). Spectral data are in accordance with
those reported in the literature.23 1H NMR (400 MHz, CDCl3):
(240 mg; 90%). Mp: 62e63 ꢁC; IR (neat):
n
¼2954, 2230, 1701, 1579,
1476, 1448, 1345, 1272, 1074, 1022, 909, 788, 732 cmꢂ1
;
1H NMR
(400 MHz, CDCl3):
d
¼1.51 (d, J¼7.0 Hz, 3H, Me), 1.99e2.17 (m, 2H,
d
¼1.73e1.82 (m, 4H, PhSeeCH2eCH2eCH2), 2.96 (t, J¼6.9 Hz, 2H,
NeCH2eCH2), 3.30 (sext., J¼6.9 Hz, 1H, SeeCH), 3.86e4.04 (m, 2H,
NeCH2), 7.27e7.36 (m, 3H, arom.), 7.44e7.52 (m, 2H, arom.),
7.56e7.64 (m, 3H, arom.), 7.80e7.76 (m, 2H, arom.); 13C NMR
PhSeeCH2), 3.46 (q, J¼6.8 Hz, 2H, NHeCH2), 7.23e7.26 (m, 3H,
arom.), 7.41e7.50 (m, 5H, arom.), 7.71e7.72 (m, 2H, arom.), NH is
missing; 13C NMR (100 MHz, CDCl3):
CH2eCH2eCH2), 29.8 (PhSeeCH2), 39.5 (NHeCH2), 127.0 (3CH
arom.), 128.7 (2CH arom.), 129.2 (2CH arom.), 130.2 (C arom.), 131.5
(CH arom.), 133.8 (2CH arom.), 134.8 (C arom.), 167.7 (CO).
d
¼27.5 (2CH2, PhSee
(100 MHz, CDCl3):
d
¼22.5 (Me), 35.2 (NeCH2eCH2), 36.1 (SeeCH),
46.7 (NeCH2), 111.1 (CN), 127.9 (C arom.), 128.2 (CH arom.), 128.7
(4CH arom.), 129.2 (2CH arom.), 131.0 (C arom.), 133.3 (CH arom.),
135.8 (2CH arom.), 168.4 (CO); HRMS calcd for C18H18ON2SeNa
([MþNa]þ) 381.0477, found 381.0479.
4.2.2.9. N-Cyano-(3-Phenylselanyl-propyl)-benzamide
(11a). Following GP5 with 10a (1.64 mmol; 524 mg), 11a was pu-
rified by flash column chromatography (petroleum ether/
EtOAc¼3:1) and isolated as a pale yellow oil (491 mg; 87%). IR
4.2.2.13. N-cyano-N-(3-methyl-3-(phenylselanyl)butyl)benza-
mide (23). Following GP4 with 21 (0.71 mmol; 172 mg), amide 22
was purified by flash column chromatography (petroleum ether/
Et2O¼1:1) and isolated as awhite solid (120 mg; 49%). Following GP5
with 22 (0.29 mmol; 100 mg), acylcyanamide 23 was purified by
flash column chromatography (pentane/Et2O¼5:1) and isolated as
(neat):
n
¼2230, 1700, 1578, 1477, 1447, 1437, 1269, 1113, 1021, 691,
670 cmꢂ1
;
1H NMR (400 MHz, CDCl3):
d
¼2.17e2.24 (m, 2H,
PhSeeCH2eCH2), 2.98 (t, J¼7.1 Hz, 2H, PhSeeCH2), 3.89 (t, J¼7.0 Hz,
2H, NeCH2), 7.26e7.30 (m, 3H, arom.), 7.47e7.50 (m, 2H, arom.),
7.54e7.60 (m, 3H, arom.), 7.78e7.80 (m, 2H, arom.); 13C NMR
a pale yellow oil (65 mg; 60%). IR (neat):
n
¼2956, 2230, 1702, 1599,
1579, 1448, 1345, 1270, 1075, 694 cmꢂ1; 1H NMR (400 MHz, CDCl3):
(100 MHz, CDCl3):
d
¼24.2 (PhSeeCH2eCH2), 28.2 (PhSeeCH2), 47.7
d
¼1.45 (s, 6H, 2Me), 1.93e1.97 (m, 2H, NeCH2eCH2), 4.02e4.06 (m,
(NeCH2),111.1 (CN),127.6 (CH arom.),128.7 (4CH arom.),129.3 (2CH
arom.), 129.4 (C arom.), 131.0 (C arom.), 133.3 (CH arom.), 133.4
(2CH arom.),168.5 (CO); HRMS calcd for C17H16N2OSeNa ([MþNa]þ)
367.0321, found 367.0321.
2H, NeCH2), 7.33e7.42 (m, 3H, arom.), 7.48e7.50 (m, 2H, arom.),
7.57e7.61 (m,1H, arom.), 7.67e7.69 (m, 2H, arom.), 7.78e7.80 (m, 2H,
arom.); 13C NMR (100 MHz, CDCl3):
d¼30.1 (2Me), 40.3
(NeCH2eCH2), 44.2 (Me2C), 46.0 (NeCH2),111.2 (CN),127.2 (C arom.),
128.7 (2CH arom.), 128.7 (2CH arom.), 129.1 (3CH arom.), 131.1 (C
arom.), 133.3 (CH arom.), 138.4 (2CH arom.), 168.4 (CO); HRMS
calcd for C19H20N2OSeNa ([MþNa]þ) 395.0633, found 395.0633.
4.2.2.10. N-Cyano-(3-phenylselanyl-propyl)-benzamide
(11b). Following GP5 with 10b (0.85 mmol; 283 mg), 11b was puri-
fied by flash column chromatography (petroleum ether/EtOAc¼7:3)
and isolated as a pale yellow oil (258 mg; 85%). IR (neat):
n
¼2928,
4.2.3. Cyclized quinazolinones
2232, 1705, 1438, 1329, 1279, 730, 711, 686, 652 cmꢂ1
(400 MHz, CDCl3):
;
1H NMR
4.2.3.1. Deoxyvasicinone (1). Following GP6 with N-acylcyana-
mide 11a (1.41 mmol; 484 mg), 127 was purified by flash column
chromatography (pentane then CH2Cl2/EtOAc¼1:1) and isolated as
a white solid (171 mg; 65%). Spectral data are in accordance with
those described in the literature.24 Mp: 105e106 ꢁC; IR (neat):
d
¼1.78e1.97 (m, 4H, PhSeeCH2eCH2eCH2), 2.96
(t, J¼7.1 Hz, 2H, PhSeeCH2), 3.77 (t, J¼7.1 Hz, 2H, NeCH2), 7.25e7.28
(m, 3H, arom.), 7.44e7.61 (m, 5H, arom.), 7.74e7.77 (m, 2H, arom.);
13C NMR (100 MHz, CDCl3):
d¼26.9, 27.1 (PhSeeCH2eCH2eCH2), 27.8
(PhSeeCH2), 47.3 (NeCH2), 111.1 (CN), 127.2 (CH arom.), 128.7 (4CH
arom.),129.3 (2CH arom.),129.8 (C arom.),131.1 (C arom.),133.2 (2CH
arom.), 133.3 (2CH arom.), 168.5 (CO); HRMS calcd for C18H18N2O-
SeNa ([MþNa]þ) 381.0477, found 381.0481.
n
¼2962, 2924, 1670, 1609, 1483, 1424, 1334, 770, 693 cmꢂ1; 1H NMR
(400 MHz, CDCl3):
d
¼2.25 (quint., J¼7.8 Hz, 2H, NeCH2eCH2), 3.14
(t, J¼7.9 Hz, 2H, CeCH2), 4.17 (t, J¼7.3 Hz, 2H, NeCH2), 7.40 (ddd,
J¼7.4, 6.8, 1.3 Hz,1H, arom.), 7.59e7.60 (m, 1H, arom.), 7.66e7.70 (m,
1H, arom.), 8.23 (dd, J¼8.0, 1.4 Hz, 1H, arom.). 13C NMR (100 MHz,
4.2.2.11. 3-Phenylselanyl-butyl-cyanamide (16). To a solution of
cyanogen bromide (1.9 mmol; 1.2 equiv; 219 mg) in Et2O (3 mL) at
ꢂ15 ꢁC were added Na2CO3 (3.18 mmol; 2 equiv; 337 mg) and amine
15 (1.59 mmol; 363 mg). The reaction mixture was stirred for 2 h at
ꢂ15 ꢁC, allowed to reach rt, and filtered through a short pad of silica.
The filtrate was concentrated under reduced pressure and purified
by flash column chromatography (petroleum ether/Et2O¼1:2) to
afford cyanamide 16 as a pale yellow oil (310 mg; 77%). This product
proved unstable and was immediately used for the next step. IR
CDCl3):
d¼19.5 (NeCH2eCH2), 32.6 (CeCH2), 46.5 (NeCH2), 120.5 (C
arom.), 126.2 (CH arom.), 126.4 (CH arom.), 126.8 (CH arom.), 134.1
(CH arom.), 149.2 (C arom.), 159.5 (NeCeN), 161.0 (CO); HRMS
calcd for C11H11O1N2 ([MþH]þ) 187.0866, found 187.0866.
4.2.3.2. Mackinazolinone (2). Following GP6 with N-acylcyana-
mide 11b (0.46 mmol; 164 mg), 2 was purified by flash column
chromatography (pentane, then CH2Cl2/EtOAc¼1:1) and isolated as
a white solid (47 mg; 51%). Spectral data are in accordance with
(neat):
n
¼3198, 2918, 2217, 1578, 1476, 1436, 1375, 1246, 1158, 1066,
those described in the literature.24 Mp: 95e96 ꢁC; IR (neat):
n
¼2955,
1021, 999, 738, 691 cmꢂ1
;
1H NMR (400 MHz, CDCl3):
d¼1.42 (d,
1658, 1610, 1583, 1564, 1467, 772 cmꢂ1; 1H NMR (400 MHz, CDCl3):
J¼7.0 Hz, 3H, Me),1.81e1.87 (m, 2H, NeCH2eCH2), 3.17e3.21 (m, 2H,
NeCH2), 3.24e3.32 (m, 1H, SeeCH), 4.35 (br s, 1H, NH), 7.23e7.29
(m, 3H, arom.), 7.52e7.54 (m, 2H, arom.); 13C NMR (100 MHz,
d
¼1.90e2.02 (m, 4H, NeCH2eCH2eCH2), 2.97 (t, J¼6.7 Hz, 2H,
CeCH2), 4.06 (t, J¼6.3 Hz, 2H, NeCH2), 7.39 (ddd, J¼7.6, 7.0, 1.1 Hz,
1H, arom.), 7.55e7.58 (m, 1H, arom.), 7.66e7.69 (m, 1H, arom.), 8.23
CDCl3):
d
¼22.5 (Me), 36.1 (SeeCH), 37.1 (NeCH2eCH2), 44.5
(d, J¼7.3, 1.4 Hz, 1H, arom.). 13C NMR (100 MHz, CDCl3):
¼19.4
d
(NeCH2), 116.4 (CN), 127.9 (CH arom.), 128.1 (C arom.), 129.1 (2CH
arom.),135.3 (2CH arom.); HRMS calcd for C11H14N2SeNa ([MþNa]þ)
277.0214, found 277.0215.
(NeCH2eCH2), 22.2 (CeCH2eCH2), 32.1 (CeCH2), 42.4 (NeCH2),
120.5 (C arom.), 126.2 (CH arom.), 126.5 (CH arom.), 126.7 (CH
arom.),134.3 (CH arom.),147.5 (C arom.),155.0 (NeCeN),162.3 (CO);
HRMS calcd for C12H13N2O ([MþH]þ) 201.1022, found 201.1023.
4.2.2.12. N-Cyano-(3-phenylselanyl-butyl)-benzamide
a solution of cyanamide 16 (0.75 mmol; 190 mg) in CH2Cl2 (20 mL)
at 0 ꢁC were added NEt3 (1.5 mmol; 2 equiv; 211
L) and benzoyl
chloride (0.97 mmol; 1.3 equiv; 113 L). The reaction mixture was
stirred for 15 min at 0 ꢁC and 14 h at rt, concentrated under reduced
(17). To
4.2.3.3.
a-Methyldeoxyvasicinone (3). Following GP6 with N-
m
acylcyanamide 17 (0.45 mmol; 162 mg), 3 was purified by flash
column chromatography (CH2Cl2/EtOAc¼10:1 to 1:1) and isolated
m

M.-H. Larraufie et al. / Tetrahedron 69 (2013) 7699e7705
7705
M.; Ollivier, C. In Encyclopedia of Radicals in Chemistry, Biology and Materials;
Studer, A., Chatgilialoglu, C., Eds.; John Wiley & Sons: Chichester, UK, 2012; Vol.
2, pp 729e766.
2. Nicolaou, K. C.; Edmonds, D. J.; Bulger, P. J. Angew. Chem., Int. Ed. 2006, 45,
7134e7186.
as a white solid (68 mg; 76%). Spectral data are in accordance with
those described in the literature.25 Mp: 120e121 ꢁC; IR (neat):
n
¼2965, 2928, 1663, 1609, 1560, 1468, 782, 734 cmꢂ1
;
1H NMR
(400 MHz, CDCl3):
d
¼1.45 (d, J¼7.0 Hz, 3H, Me), 1.83 (dq, J¼12.9,
3. (a) Servais, A.; Azzouz, M.; Lopes, D.; Courillon, C.; Malacria, M. Angew. Chem.,
8.5 Hz, 1H, NeCH2eCHH), 2.39e2.51 (m, 1H, NeCH2eCHH),
3.23e3.33 (m, 1H, MeeCH), 3.91e4.01 (m, 1H, NeCHH), 4.23 (ddd,
J¼12.4, 8.7, 3.9 Hz, 1H, NeCHH), 7.40 (ddd, J¼8.2, 6.7, 1.6 Hz, 1H,
arom.), 7.62e7.70 (m, 2H, arom.), 8.22e8.25 (m, 1H, arom.). 13C
^
Int. Ed. 2007, 46, 576e579; (b) Larraufie, M.-H.; Courillon, C.; Ollivier, C.; Lacote,
E.; Malacria, M.; Fensterbank, L. J. Am. Chem. Soc. 2010, 132, 4381e4387; (c)
^
Larraufie, M.-H.; Ollivier, C.; Fensterbank, L.; Malacria, M.; Lacote, E. Angew.
Chem., Int. Ed. 2010, 49, 2178e2181; (d) Maestri, G.; Larraufie, M.-H.; Ollivier, C.;
^
Malacria, M.; Fensterbank, L.; Lacote, E. Org. Lett. 2012, 14, 5538e5541. For
NMR (100 MHz, CDCl3):
d
¼17.2 (Me), 28.6 (NeCH2eCH2), 38.8
reviews on the chemistry of cyanamides, see; (e) Nekrasov, D. D. Russ. J. Org.
(MeeCH), 44.6 (NeCH2), 120.7 (C arom.), 126.2 (CH arom.), 126.4
(CH arom.), 127.0 (CH arom.), 134.1 (CH arom.), 149.4 (C arom.),
161.0 (NeCeN), 162.4 (CO); HRMS calcd for C12H12N2ONa
([MþNa]þ) 223.0842, found 223.0843.
Chem. 2004, 40, 1387e1402; (f) Larraufie, M.-H.; Maestri, G.; Malacria, M.; Ol-
^
livier, C.; Fensterbank, L.; Lacote, E. Synthesis 2012, 44, 1279e1292.
4. Amin, A. H.; Mehta, D. R. Nature 1959, 183, 1317e1318.
5. Al-Shamma, A.; Drake, S.; Flynn, D. L.; Mitscher, L. A.; Park, Y. H.; Rao, G. S. R.;
Simpson, A.; Swayze, J. K.; Veysoglu, T.; Wu, S. T. S. J. Nat. Prod. 1981, 44,
745e747.
6. Mori, M.; Kobayashi, H.; Kimura, M.; Ban, Y. Heterocycles 1997, 46, 541e543.
7. Akazome, M.; Kondo, T.; Watanabe, Y. J. Org. Chem. 1993, 58, 310e312.
8. Takeuchi, H.; Hagiwara, S.; Eguchi, S. Tetrahedron 1989, 45, 6375e6378.
9. Bowman, W. R.; Elsegood, M. R. J.; Stein, T.; Weaver, G. W. Org. Biomol. Chem.
2007, 5, 103e113.
4.2.3.4.
a,a
0-Dimethyldeoxyvasicinone (4). Following GP6 with
N-acylcyanamide 23 (0.08 mmol; 30 mg), 130 was purified by flash
column chromatography (CH2Cl2/EtOAc¼10:1 to 1:1) and isolated
as a white solid (15 mg; 87%). Spectral data are in accordance with
those described in the literature. Mp: 128e129 ꢁC; IR (neat):
10. Johns, S. R.; Lamberton, J. A. J. Chem. Soc., Chem. Commun. 1965, 267e269.
11. (a) Hart, N. K.; Johns, S. R.; Lamberton, J. A. Aust. J. Chem. 1971, 24, 223e224; (b)
Liu, J. F.; Wilson, C. J.; Ye, P.; Sprague, K.; Sargent, K.; Si, Y.; Beletsky, G.; Yo-
hannes, D.; Ng, S. C. Bioorg. Med. Chem. Lett. 2006, 16, 686e690.
n
¼2961, 1671, 1613, 1470, 772 cmꢂ1
;
1H NMR (400 MHz, CDCl3):
d
¼1.43 (s, 6H, 2Me), 2.10 (t, J¼7.2 Hz, 2H, CeCH2), 4.12 (t, J¼7.2 Hz,
€
€
12. Hermecz, I.; Vasvari-Debreczy, L.; Horvath, A.; Balogh, M.; Kokosi, J.; DeVos, C.;
Rodriguez, L. J. Med. Chem. 1987, 30, 1543e1549.
2H, NeCH2), 7.41e7.43 (m, 1H, arom.), 7.70e7.72 (m, 2H, arom.),
8.28 (d, J¼8.1 Hz, 1H, arom.). 13C NMR (100 MHz, CDCl3):
¼26.1
d
13. Elmuradov, B. Z.; Shakhidoyatov, K. M. Chem. Nat. Compd. 2004, 40,
496e498.
(2Me), 35.6 (NeCH2eCH2), 43.2 (NeCH2), 43.6 (Me2C), 120.9 (C
arom.), 126.2 (CH arom.), 126.5 (CH arom.), 127.3 (CH arom.), 134.1
(CH arom.), 149.8 (C arom.), 161.3 (NeCeN), 165.1 (CO). HRMS
calcd for C13H14N2ONa ([MþNa]þ) 237.0998, found 237.0995.
14. (a) Clive, D. L. J.; Chittattu, G.; Wong, C. K. J. Chem. Soc., Chem. Commun. 1978,
41e42; (b) Clive, D. L. J.; Chittattu, G. J.; Farina, V.; Kiel, W. A.; Menchen, S. M.;
Russell, C. G.; Singh, A.; Chi Kwong Wong, C. K.; Curtis, N. J. J. Am. Chem. Soc.
1980, 102, 4438e4447 For a review, see; (c) Renaud, P. Top. Curr. Chem. 2000,
208, 81e112.
15. Bowman, W. R.; Stephenson, P. T.; Terrett, N. K.; Young, A. R. Tetrahedron 1995,
51, 7959e7980.
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ꢀ
We thank CNRS, UPMC, IUF (M.M., L.F.), the region Ile-de-France
(M.-H.L.) and ANR (grant Credox) for funding of this work. Ana-
lytical equipment was generously offered through FR 2769.
Supplementary data
1H and 13C NMR spectra of substrates 11a,b, 17, 23 as well as
polycyclic compounds 1e4. Supplementary data related to this ar-
ticle can be found at http://dx.doi.org/10.1016/j.tet.2013.05.058.
23. Toshimitsu, A.; Hirosawa, C.; Tanimoto, S.; Uemura, S. Tetrahedron Lett. 1992, 33,
4017e4020.
24. Liu, J.-F.; Ye, P.; Sprague, K.; Sargent, K.; Yohannes, D.; Baldino, C. M.; Wilson, C.
References and notes
J.; Ng, S.-C. Org. Lett. 2005, 7, 3363e3366.
25. Elmuradov, B. Z.; Shakhidoyatov, K. M. Chem. Nat. Compd. 2005, 40, 496e498.
1. For a recent review on radical cascades: Baralle, A.; Baroudi, A.; Daniel, M.;
Fensterbank, L.; Goddard, J.-P.; Lacote, E.; Larraufie, M.-H.; Maestri, G.; Malacria,
^