Intramolecular "hydroiminiumation and -amidiniumation" of alkenes: A convenient, flexible, and scalable route to cyclic iminium and imidazolinium salts

Article abstract of DOI:10.1021/jo0703909

(Chemical Equation Presented) Addition of a stoichiometric amount of HCl to alkenylaldimines, -formamidines, and -amidines results in the protonation of the sp²-nitrogen atom. The resulting alkenylaldiminium, -formamidinium, and -amidinium salt

Full text of DOI:10.1021/jo0703909

Intramolecular “Hydroiminiumation and -amidiniumation” of
Alkenes: A Convenient, Flexible, and Scalable Route to Cyclic
Iminium and Imidazolinium Salts
Rodolphe Jazzar, Jean-Baptiste Bourg, Rian D. Dewhurst, Bruno Donnadieu, and
Guy Bertrand*
UCR-CNRS Joint Research Chemistry Laboratory (UMI 2957), Department of Chemistry,
UniVersity of California, RiVerside, California 92521-0403
gbertran@ucr.edu
ReceiVed February 28, 2007
Addition of a stoichiometric amount of HCl to alkenylaldimines, -formamidines, and -amidines results
in the protonation of the sp2-nitrogen atom. The resulting alkenylaldiminium, -formamidinium, and
-amidinium salts can be isolated and fully characterized, including single-crystal X-ray diffraction studies.
Heating solutions of these salts induces ring closure cleanly and regioselectively via formal “exo” addition
of the nitrogen-hydrogen bond to the pendent carbon-carbon double bond, affording the corresponding
cyclic aldiminium, dihydroisoquinolinium, and imidazolinium salts. Of special interest, novel 4,4-
disubstituted imidazolinium salts are accessible via this synthetic route. Similarly, addition of phosgene
to alkenyl ureas and alkenyl amides, followed by gentle heating, cleanly affords C-chloro imidazolinium,
and cyclic C-chloro iminium salts, respectively. Treatment of the latter with tetrakis(triphenylphosphine)-
palladium allows for the preparation of the first transition-metal complex bearing a cyclic arylaminocarbene
as ligand. Deuterium labeling experiments suggest that the mechanism of the hydroiminiumation and
-amidiniumation reactions involves an intramolecular proton transfer to the double bond in the rate-
determining step. This novel synthetic methodology gives access to a variety of N-heterocyclic carbene
(NHC) and cyclic alkyl- and arylaminocarbene (CAAC) precursors.
SCHEME 1
Introduction
Imidazolinium A (Scheme 1) and imidazolium salts have
found numerous applications as room-temperature ionic liquids,
of particular importance for “Green Chemistry”,1 but also for
dye-sensitized solar cells, electrochemical devices, wet double-
layer capacitors, and ion transport systems.2 When R ) H, they
(1) (a) Anastas, P. T.; Williamson, T. C. Green Chemistry: Frontiers
in Benign Chemical Syntheses and Processes; Oxford University Press: New
York, 1999. (b) Wasserscheid, P.; Welton, T. Ionic Liquids in Synthesis;
Wiley-VCH: Weinheim, 2003. (c) Dupont, J.; de Souza, R. F.; Suarez, P.
A. Z. Chem. ReV. 2002, 102, 3667-3691. (d) Wasserscheid, P.; Keim, W.
Angew. Chem., Int. Ed. 2000, 39, 3773-3789.
serve as direct precursors for free Arduengo-type carbenes
(NHCs)3,4 and for the introduction of NHC ligands into transition
metal based catalysts;5 the chloro analogues (R ) Cl) can also
be used for the latter application.6 As recently noted by Fu¨rstner
et al.,7 despite a huge number of structural variants, several
(2) Ohno, H. Electrochemical Aspects of Ionic Liquids; Wiley-Inter-
science: New York, 2005.
10.1021/jo0703909 CCC: $37.00 © 2007 American Chemical Society
Published on Web 04/05/2007
3492
J. Org. Chem. 2007, 72, 3492-3499

Intramolecular “Hydroiminiumation and -amidiniumation” of Alkenes
obvious and seemingly trivial substitution patterns for these
dinitrogen-containing heterocyclic salts are as yet unknown or
very rare. Among them are the unsymmetrical versions, and
particularly 4,4-disubstituted imidazolinium salts A′.7,8 These
limitations stem from the scarcity of viable synthetic routes.
Moreover, it is astounding to note that the classical route to
imidazolinium salts9 involves the use of NaBH4 as a reducing
agent, which turns out to be rather expensive from an industrial
point of view, and even more importantly from a “Green
Chemistry” perspective, poses many environmental and re-
cycling challenges. Among the alternative synthetic methods,10
the most common relies on N-substitution of appropriate
imidazoline precursors, which is only possible with a small
number of reactive electrophiles.
Because saturated nitrogen-containing heterocycles form the
core structures, and are key intermediates, of many natural
products,11 several synthetic methods for their preparation have
been developed. Among them is the intramolecular hydroami-
nation of alkenes, in which the nitrogen-carbon bond is formed
by addition of an amine N-H bond to an olefin.12 Various
catalysts have been used to effect this transformation, and
importantly, it has been shown recently that when weakly basic
amines are used, the hydroamination can be catalyzed by
Bro¨nsted acids.13 Recognizing that imines are less basic than
amines, we have studied the feasibility of “hydroiminiumation”
reactions and recently reported preliminary results.14 We showed
that the addition of a stoichiometric amount of HCl to alkenyl
imines resulted in the formation of the N-protonated species B,
which underwent, under gentle heating, a ring closure cleanly
and regioselectively, leading to the cyclic iminium salts C
(Scheme 1). Importantly, salts C are the direct precursors of
stable cyclic alkylaminocarbenes (CAACs).15 We have shown
that CAACs can compete with NHCs as ligands for transition-
metal-based catalysts15a and also allow the preparation of very
low coordinate transition-metal centers.15b
We report herein examples of an asymmetric version of the
hydroiminiumation reaction and the extension of our approach
to the synthesis of dihydroisoquinolinium salts as well as cyclic
C-chloro iminium salts. We show that the N-H bond of
amidinium salts also adds to a pendent carbon-carbon double
bond giving a straightforward, atom-economical route to imi-
dazolinium salts, especially those of type A′. Last, the mech-
anism of this ring-closing reaction is discussed on the basis of
isotopic labeling experiments.
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Results and Discussion
We have already shown that relatively bulky electrophiles
(such as the 1,2-epoxy-2-methylpropane) approach the cyclo-
hexane moiety of the aza-allyl anion prepared from the aldimine
1a [derived from (-)-menthone] exclusively from the equatorial
direction.15a Therefore, despite the fact that 1a exists as a 90/
10 mixture of diastereomers, addition of 3-bromo-2-methylpro-
pene to its lithium salt led to the enantiomerically pure
alkenylaldimine 2a in 94% yield (Scheme 2). After addition of
HCl to form the alkenylaldiminium salt 3a, the cyclization
occurred readily and was complete after 5 h at 50 °C. The
optically pure cyclic iminium salt 4a was isolated in 92% yield
(by the previously reported method, 4a was obtained in only
41% yield).
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J. Org. Chem, Vol. 72, No. 9, 2007 3493

Jazzar et al.
SCHEME 2
SCHEME 3
SCHEME 4
diffraction study unambiguously proved the alkenyl formami-
dinium structure of 10a (Figure 2, left). We were pleased to
observe that heating a toluene or acetonitrile solution of 10a in
a flask sealed by a Teflon stopcock at 135 °C for 36 h afforded
the desired imidazolinium salt 11a as a racemate in 83% yield
(Figure 2, right) (Scheme 4). Similarly, alkenylformamidines
9b-d, prepared from the corresponding formamidines in high
yields, were found to be suitable precursors for 4,4-disubstituted
imidazolinium salts 11b-d. The protonation/cyclization se-
quence was performed in situ. Imidazolinium salt 11b was
isolated in 80% yield after heating for 24 h at 110 °C. When
the Dipp substituents of 10b were replaced by mesityl groups,
the cyclization required heating at 135 °C for 12 h, and
heterocyclic salt 11c was isolated in 78% yield. Under the same
experimental conditions, imidazolinium salt 11d featuring 2,6-
difluorophenyl groups was also obtained in 79% yield from 9d,
illustrating the broad scope of application of this synthetic route.
Since the N-substitution of formamidines by reactive elec-
trophiles is a well-known reaction, it quickly became apparent
that the above synthesis of imidazolinium salts could be
simplified even further. Indeed, allyl bromide and 3-bromo-2-
methylpropene are quite reactive as electrophiles, and in the
process of the substitution of formamidine 8a, one equivalent
of HBr is liberated, protonating the remaining nitrogen. Thus,
heating an equimolar toluene solution of allyl bromide and
formamidine 8a in a tube sealed by a Teflon stopcock at 135
°C for 36 h afforded imidazolinium salt 11a, which was isolated
in 66% yield. The one-pot procedure appeared to occur at a
slightly lower temperature when 3-bromo-2-methylpropene was
used. The reaction was complete after 24 h at 110 °C and
imidazolinium salt 11b, featuring two methyl groups in the 4
position, was isolated in 70% yield (Scheme 5).
that heating 3b in acetonitrile at 100 °C for 12 h cleanly afforded
the desired heterocyclic salt 4b, isolated in 86% yield, with an
82% de (according to 1H NMR spectroscopy) (Scheme 2). The
absolute configuration of the major diastereomer was assigned
by single-crystal X-ray crystallography (Figure 1).
To demonstrate further the generality of the hydroiminiuma-
tion route, we turned our attention to the preparation of 3,4-
dihydroisoquinolinium salts. Although several synthetic routes
are available for such heterocycles, 6,6-disubstituted derivatives
featuring a bulky substituent at nitrogen are attainable only
through addition of an electrophile to the nitrogen of the
corresponding dihydroisoquinoline, thus placing severe restric-
tions on the size of the N-substituent;16 they are highly desirable
precursors for the preparation of the as yet unknown stable cyclic
arylaminocarbenes.17 Starting from the readily available aldimine
5, a lithium-halogen exchange with n-BuLi, followed by
addition of 3-bromo-2-methylpropene quantitatively led to the
desired precursor 6. Then, addition of HCl and heating at 110
°C for 24 h afforded the 6,6-dimethyldihydroisoquinolinium salt
7, which was isolated in 95% yield (Scheme 3).
Despite the greater basicity of amidines over imines, it was
decided to investigate the possibility of extrapolating this ring-
closure protocol to the synthesis of imidazolinium salts A.
Deprotonation of 8a with n-BuLi followed by addition of allyl
chloride afforded the corresponding alkenyl formamidine 9a in
94% yield (Scheme 4). Addition of a stoichiometric amount of
a 2 M solution of HCl/Et2O to a toluene or ether solution of 9a
resulted in the formation of a precipitate. After filtration and
recrystallization from chloroform, a new compound 10a was
isolated as white crystals in 95% yield. A doublet resonance in
the 1H NMR spectrum at 14.0 ppm (JHH ) 12.0 Hz) suggested
the protonation of one nitrogen atom. A single-crystal X-ray
The cyclization process is not restricted to formamidines.
When a phenyl substituent is present at the NCN carbon and
given bulky groups at nitrogen, the allylation of 12 may be
(16) (a) Chrzanowska, M.; Rozwadowska, M. D. Chem. ReV. 2004, 104,
3441-3370. (b) Bohe, L.; Kammoun, M.; Tetrahedron Lett. 2002, 43, 803-
805. (c) Bulman Page, P. C.; Buckley, B. R.; Appleby, L. F.; Alsters, P. A.
Synthesis 2005, 3405-3411.
(17) A few stable acyclic (aryl)(amino)carbenes have been reported: (a)
Sole, H.; Gornitzka, H.; Schoeller, W. W.; Bourissou, D.; Bertrand, G.
Science 2001, 292, 1901-1903. (b) Cattoe¨n, X.; Gornitzka, H.; Bourissou,
D.; Bertrand, G. J. Am. Chem. Soc. 2004, 126, 1342-1343.
FIGURE 1. Molecular structure of the major isomer of the cyclic
aldiminium salt 4b in the solid state.
3494 J. Org. Chem., Vol. 72, No. 9, 2007

Intramolecular “Hydroiminiumation and -amidiniumation” of Alkenes
FIGURE 2. Molecular structures of alkenyl formamidinium salt 10a (left) and imidazolinium salt 11a (right) in the solid state.
SCHEME 5
SCHEME 8
SCHEME 6
SCHEME 7
iminum salts are effective proligands for transition-metal
complexes, 17a was treated with palladium tetrakis(tri-
phenylphosphine). Indeed, palladium(II) complex 18a was
isolated in 55% yield and fully characterized including a single-
crystal X-ray diffraction study (Figure 3).
In order to gain more insight into the mechanism of the
cyclization process, deuterium labeling experiments were carried
out using 2c and 9a as starting materials. In both cases, only
one deuterated compound (4cD and 11cD, respectively) was
obtained (Scheme 9). These observations argue against a
reversible protonation of the alkene, since in this case mono-
and polydeuterated derivatives would be obtained. Of special
importance is the exclusive formation of 4cD. If an inter-
molecular protonation of the olefin were to occur, we would
expect little or no preference for deuteration at either olefinic
performed via its corresponding lithium salt. Then, after
protonation with HCl, the ring closure leading to 13 is complete
after 12 h at 105 °C (Scheme 6).
As mentioned in the introduction, C-chloro imidazolinium
salts can be used to introduce the corresponding NHCs as
ligands for transition-metal centers. Chloro amidines are clas-
sically prepared by addition of a strong chlorinating reagent
(such as phosgene or oxalyl chloride) to trisubstituted urea
derivatives, followed by elimination of HCl; obviously, this
transformation proceeds via C-chloro amidinium salts.18 There-
fore, we hypothesized that using N-allylurea 14 as a starting
material, a C-chloro amidinium salt would be formed by addition
of phosgene and this may undergo a subsequent hydroamidini-
umation reaction, affording the desired C-chloro imidazolinium
salt 15. N,N′-Diaryl-N-allylurea 14 is readily available as shown
in Scheme 7. Simple heating of a toluene solution of 14 at 80
°C for 24 h in the presence of a stoichiometric amount of
phosgene, cleanly leads to 15, which was isolated in 78% yield.
A very similar methodology can be applied to prepare
C-chloro iminium salts 17a,b. Heating 16a and 16b at 80 °C
for 24 h gave rise to 17a and 17b, which were isolated in 86
and 78% yield, respectively (Scheme 8). Since transition-metal
complexes of cyclic aminoarylcarbenes have not yet been
reported, and as a proof of principle that this type of C-chloro
FIGURE 3. Molecular structure of the palladium complex 18a (H
atoms are omitted). Selected bond distances (Å) and angles (deg): N1-
C1 1.307(7), C1-Pd 1.997(6), Pd-P 2.3514(16), Pd-Cl1 2.3088(15),
Pd-Cl2 2.2957(15); Car-C1-N1 107.8(5), C1-Pd-Cl1 88.41(15),
C1-Pd-Cl2 87.18(15), C1-Pd-P 173.87(16).
(18) Ulrich, H.; Tilley, J. N.; Sayigh, A. A. R. J. Org. Chem. 1964, 29,
2401-2404.
J. Org. Chem, Vol. 72, No. 9, 2007 3495

Jazzar et al.
SCHEME 9
1H), 7.33 (d, JHH ) 7.2 Hz, 2H), 7.27 (t, JHH ) 7.2 Hz, 1H), 5.23
and 5.04 (s × 2, 1H), 3.22 (sept, JHH ) 6.8 Hz, 2H), 2.84 (m, 2H),
2.53 (m, JHH ) 6.4 Hz, 1H), 2.23 (d, JHH ) 12.8 Hz, 1H), 2.12 (s,
3H), 2.07 (d, JHH ) 12.4 Hz, 1H), 1.89 (d, JHH ) 12.4 Hz, 1H),
1.77-1.55 (m, 4H), 1.42 (m, 12H), 1.22 (d, JHH ) 6.8 Hz, 3H),
1.16 (d, JHH ) 6.4 Hz, 3H), 1.02 (d, JHH ) 6.8 Hz, 3H); 13C{1H}
NMR (CDCl3) δ 172.1, 149.3, 142.8, 137.7, 123.9, 123.1, 116.4,
49.2, 47.7, 45.7, 44.1, 35.8, 29.3, 27.8, 26.5, 26.0, 24.0, 23.9, 23.7,
23.2, 23.1, 19.1; MS(EI) m/z 382 [M + H]+.
Synthesis of Alkenylaldimine 2b. Following the same procedure
used for 2a, but with 3-bromopropene, 2b was obtained as a light
yellow oil (89%): 1H NMR (CDCl3) δ 7.98 (s, 1H), 7.16-7.06
(m, 3H), 6.02-5.88 (m, 1H), 5.20 (s, 1H), 5.16 (s, 1H), 2.97 (sept,
JHH ) 6.8 Hz, 2H), 2.67-2.45 (m, 2H), 2.26-2.15 (m, 1H), 2.00-
1.66 (m, 4H), 1.46-1.26 (m, 4H), 1.20 (t, JHH ) 6.4 Hz, 12H),
1.00 (d, JHH ) 6.9 Hz, 3H), 1.16 (d, JHH ) 6.2 Hz, 3H,), 1.02 (d,
JHH ) 6.9 Hz, 3H); 13C{1H} NMR (CDCl3) δ 171.9, 149.3, 137.6,
134.7, 123.9, 123.1, 118.4, 48.4, 48.1, 44.9, 41.8, 35.8, 29.2, 27.7,
25.6, 24.4, 23.8, 23.7, 23.3, 23.0, 19.2; MS(EI) m/z 368 [M + H]+.
carbon, and consequently observe scrambling of the deuterium
over these two positions, since in both cases a secondary
carbocation would be formed. Therefore, it can be concluded
that the proton is transferred intramolecularly to the double bond
in the rate-determining step.
Conclusion
Synthesis of Alkenylaldiminium 3a. To a hexane solution (10
mL) of 2a (1.00 g, 2.6 mmol) at -78 °C was added a solution of
HCl in Et2O (1.30 mL, 2.0 M, 2.6 mmol). Precipitation of a white
powder was immediately observed. After 15 min, the mixture was
warmed to rt and stirred for an additional 15 min. Filtration of the
precipitate, washing with hexanes (2 × 10 mL), and drying under
vacuum afforded the alkenyliminium salt 3a as a white powder
Simple protonation of the sp2-nitrogen atom of alkenylaldi-
mines, -formamidines, and -amidines and addition of a chlori-
nating agent to alkenyl amides followed by heating are very
convenient synthetic routes to a variety of NHC and CAAC
precursors. Deuterium labeling experiments suggest that the
mechanism of the cyclization reaction involves an intramolecular
proton transfer to the double bond in the rate-determining step.
Extension of this novel methodology to related systems is under
investigation.
1
(1.01 g, 92%): mp 60-62 °C dec; H NMR (CDCl3) δ 14.66 (br
s, 1H), 8.31 (s, 1H), 7.24 (m, 3H), 5.08 (s, 1H), 4.93 (s, 1H), 3.07
(d, JHH ) 13.7 Hz, 1H), 2.95 (sept, JHH ) 6.8 Hz, 2H), 2.73 (d,
JHH ) 13.7 Hz, 1H), 2.43 (br d, JHH ) 13.0 Hz, 1H), 2.30 (sept,
JHH ) 6.4 Hz, 2H), 1.95 (s, 2H), 1.86-1.50 (m, 6H), 1.34 (m,
2H), 1.26 (dd, JHH ) 2.3 Hz, 12H), 0.99 (br t, JHH ) 7.9 Hz, 6H),
0.79 (d, JHH ) 6.8 Hz, 3H); 13C{1H} NMR (CDCl3) δ 189.9, 143.2,
139.2, 134.8, 130.7, 124.7, 119.2, 51.7, 46.6, 45.7, 42.4, 34.8, 30.7,
28.8, 26.1, 26.0, 24.2, 23.9, 23.4, 23.2, 22.5, 18.3.
Experimental Section
General Methods. All manipulations were performed under an
inert atmosphere of dry argon using standard Schlenk techniques.
Dry, oxygen-free solvents were employed. 1H and 13C NMR
chemical shifts are reported relative to residual solvent resonances.
31P and 19F NMR chemical shifts are reported relative to 85% H3-
PO4 and CFCl3, respectively.
Synthesis of Alkenylaldiminium Salt 3b. Following the same
procedure used for 3a, but starting from 2b (1.00 g, 2.7 mmol), 3b
was obtained as a white solid (0.99 g, 90%): mp 60 °C; 1H NMR
(CDCl3) δ 15.47 (br s, 1H), 8.15 (s, 1H), 7.26 (t, JHH ) 7.6 Hz,
1H), 7.13 (d, JHH ) 7.6 Hz, 2H), 5.75 (m, 1H), 5.21 (d, JHH ) 2.7
Hz, 1H, )CH2,), 5.19 (br d, 1H), 3.08 (dd, JHH ) 7.1, 13.9 Hz,
1H), 2.84 (sept, JHH ) 6.7 Hz, 2H), 2.66 (dd, JHH ) 7.1, 13.9 Hz,
1H), 2.44 (dd, JHH ) 12.8, 13.9 Hz, 1H), 2.08 (sept, JHH ) 6.5 Hz,
1H), 1.79 (d, JHH ) 12.5 Hz, 1H), 1.69 (d, JHH ) 12.5 Hz, 1H),
1.53 (br s, 1H), 1.45 (d, JHH ) 13.0 Hz, 2H), 1.22 (br s, 1H), 1.16
(d, JHH ) 6.7 Hz, 12H), 0.96 (br s, 1H), 0.99 (d, JHH ) 6.5 Hz,
6H), 0.69 (d, JHH ) 6.7 Hz, 3H); 13C{1H} NMR (CDCl3) δ 185.1,
141.5, 138.0, 131.3, 128.8, 124.0, 120.6, 50.0, 47.3, 44.7, 40.5,
34.8, 29.9, 28.3, 25.4, 23.7, 23.5, 22.9, 22.3, 18.3.
Synthesis of CAAC,H+ 4a. An oven-dried, argon-flushed,
sealable Schlenk tube with a Teflon stopcock was loaded with 3a
(1.00 g, 2.4 mmol) in CHCl3 (5 mL). The mixture was heated at
55 °C for 6 h. The volatiles were removed under vacuum to afford
4a as a white powder (0.92 g, 92%): mp 157 °C; the spectroscopic
data are similar to those reported for the trifluoromethane sulfonate
salt.15a
Synthesis of CAAC,H+ 4b. Cyclic iminium salt 4b was prepared
in one pot starting from 2b. An oven-dried, argon-flushed, sealable
Schlenk tube with a Teflon stopcock was loaded with 2b (1.00 g,
2.7 mmol) and toluene (10 mL) and was cooled to -78 °C, at which
point a solution of HCl in Et2O (1.36 mL, 2.0 M, 2.7 mmol) was
added. Precipitation of a white powder (3b) was immediately
observed. After 15 min at -78 °C, the mixture was allowed to
warm to rt and stirred for an additional 15 min. The mixture was
heated at 110 °C for 24 h, after which time the volatiles were
removed under vacuum to afford 4b as a 91:9 ratio of diastereomers
(0.86 g, 86%). The major isomer was obtained optically pure by
recrystallization from chloroform at -30 °C: mp 150 °C; 1H NMR
Synthesis of Aldimine 1a. In a Schlenk tube containing activated
molecular sieves (10 g), menthyl 3-carboxaldehyde (90/10 mixture
of diastereomers)19 (33.8 mL, 181 mmol) was added dropwise at
room temperature to a solution of 2,6-diisopropylaniline (30.6 g,
173 mmol) in toluene (100 mL). The suspension was stirred for 12
h at 100 °C. After filtration, the molecular sieves were washed with
hexane (60 mL). Evaporation of the solvent, and heating under
vacuum at 100 °C to remove all volatiles, afforded 1a (80% de) as
an oily yellow solid (52.0 g, 92%). Major diastereomer: 1H NMR
(CDCl3) δ 7.43 (d, JHH ) 7.1 Hz, 1H), 7.14-7.05 (m, 3H), 2.98
(sept, JHH ) 6.9 Hz, 2H), 2.54 (m, 1H), 1.94-1.70 (m, 4H), 1.59-
1.38 (m, 5H), 1.17 (2 × overlapping d, JHH ) 6.9 Hz, 12H), 0.97
(2 × overlapping d, JHH ) 6.5 Hz, 6H), 0.90 (d, JHH ) 6.9 Hz,
3H); 13C{1H} NMR (CDCl3) δ 171.6, 148.9, 138.0, 124.1, 123.1,
48.5, 45.2, 39.2, 35.0, 32.3, 29.5, 27.7, 23.9, 23.7, 22.8, 21.6, 15.5;
MS(HR-ESI) m/z 328.3004 [M + H]+ (calcd 328.3004).
Synthesis of Alkenylaldimine 2a. An Et2O solution (20 mL)
of Me2NLi (0.467 g, 9.2 mmol) at -78 °C was added to an Et2O
solution (20 mL) of 1a (3.00 g, 9.2 mmol) at -78 °C. After 15
min, the mixture was warmed to rt and stirred for an additional 4
h. The volatiles were removed under vacuum, affording an oily
yellow/orange residue which was dissolved in Et2O (30 mL) and
cooled to -78 °C. 3-Bromo-2-methylpropene (0.92 mL, 9.2 mmol)
was slowly added. After 15 min, the solution was warmed to rt
and stirred for an additional 12 h. Removal of the volatiles under
vacuum and extraction with hexanes afforded alkenylaldimine 2a
as a light yellow oil (3.11 g, 94%): 1H NMR (CDCl3) δ 8.21 (s,
(19) Spino, C.; Godbout, C.; Beaulieu, C.; Harter, M.; Mwene-Mbeja,
T. M.; Boisvert, L. J. Am. Chem. Soc. 2004, 126, 13312-13319.
3496 J. Org. Chem., Vol. 72, No. 9, 2007

Intramolecular “Hydroiminiumation and -amidiniumation” of Alkenes
(CD3CN) δ 10.45 (s, 1H), 7.60 (t, JHH ) 7.8 Hz, 1H), 7.46-7.42
(m, 2H), 4.87 (sext, JHH ) 7.1 Hz, 1H), 2.97 (sept, JHH ) 6.8 Hz,
2H), 2.67-2.45 (m, 2H) 2.26-2.15 (m, 1H), 2.00-1.66 (m, 4H),
13C{1H} NMR (CDCl3) δ 159.2 (d, JCF ) 226.0 Hz), 156.4 (dd,
JCF ) 244.1, 6.0 Hz), 155.8, 140.6, 128.2 (t, JCF ) 8.8 Hz), 122.4
(t, JCF ) 9.6 Hz), 114.1, 112.4 (d, JCF ) 22.4 Hz), 111.5 (br s),
51.7, 20.0; MS(EI) m/z 323 [M + H]+.
1.46-1.26 (m, 4H), 1.20 (t, JHH ) 6.4 Hz, 12H), 1.00 (d, JHH
)
6.9 Hz, 3H), 1.16 (d, JHH ) 6.2 Hz, 3H), 1.02 (d, JHH ) 6.9 Hz,
3H); 13C{1H} NMR (CD3CN) δ 194.6, 145.6, 144.3, 133.1, 132.0,
126.7, 126.5, 72.8, 60.2, 50.3, 48.5, 40.6, 35.9, 31.1, 30.3, 29.9,
27.4, 26.6, 25.4, 24.0, 23.7, 23.5, 23.3, 22.6, 19.1, 18.4; MS(ESI)
m/z 368 [M]+.
Synthesis of Alkenylformamidinium 10a. Following the pro-
cedure described for the synthesis of 3a, derivative 10a was obtained
from 9a as a white powder (95%). Crystals were grown from
1
chloroform: mp 151 °C dec; H NMR (CDCl3) δ 14.0 (d, JHH
)
12.0 Hz, 1H), 7.52-7.40 (m, 1H), 7.36-7.19 (m, 6H), 5.97 (m,
1H), 5.64 (d, JHH ) 16.9 Hz, 1H), 5.38 (d, JHH ) 10.0 Hz, 1H),
5.14 (d, JHH ) 7.1 Hz, 2H), 3.27 (sept, JHH ) 6.8 Hz, 2H), 3.00
(sept, JHH ) 6.8 Hz, 2H), 1.40 (br d, JHH ) 6.8 Hz, 6H), 1.32 (d,
Synthesis of Alkenylaldimine 6. A solution of n-BuLi in
hexanes (3.6 mL, 1.6 M, 5.8 mmol) was added dropwise to an Et2O
solution (20 mL) of 520 (2.00 g, 5.8 mmol) at -78 °C. After 15
min, the mixture was warmed to rt and stirred for an additional 1
h. The mixture was then cooled to -78 °C, and 3-bromo-2-
methylpropene (0.59 mL, 5.8 mmol) was slowly added. After 15
min, the solution was warmed to rt and stirred for an additional 12
h. Removal of the volatiles under vacuum and extraction with
hexanes afforded 6 as a light yellow oil (1.80 g, 97%): 1H NMR
(CDCl3) δ 8.49 (s, 1H), 8.32-8.28 (m, 1H), 8.32-8.28 (m, 1H),
7.50-7.44 (m, 2H), 7.33-7.30 (m, 1H), 7.26-7.18 (m, 2H), 4.89
(s, 1H), 4.48 (s, 1H), 3.61 (s, 2H), 3.07 (sept, JHH ) 6.8 Hz, 2H),
1.83 (s, 3H), 1.24 (d, JHH ) 6.8 Hz, 12H); 13C{1H} NMR (CDCl3)
δ 160.7, 149.8, 145.2, 140.0, 137.8, 134.6, 131.3, 131.1, 127.6,
127.2, 124.2, 123.2, 112.7, 40.9, 28.1, 23.7, 23.3; MS(EI) m/z 320
[M + H]+.
Synthesis of Dihydroisoquinolinium 7. Salt 7 was prepared
from 6 following the same procedure as for the synthesis of 4b.
Precipitation of the residue from Et2O afforded 7 as a white powder
(95%): mp 118 °C; 1H NMR (CDCl3) δ 9.98 (s, 1H), 8.73 (d, JHH
) 7.6 Hz, 1H), 7.82 (br dd, 1H), 7.80-7.47 (m, 3H), 7.31 (d, JHH
) 7.9 Hz, 2H), 3.54 (s, 2H), 2.77 (sept, JHH ) 6.8 Hz, 2H), 1.43
(s, 6H), 1.33 (d, JHH ) 6.8 Hz, 6H), 1.21 (d, JHH ) 6.8 Hz, 6H);
13C{1H} NMR (CDCl3) δ 172.0, 143.8, 139.5, 138.1, 136.7, 135.0,
131.2, 129.0, 125.1, 125.0, 67.8, 40.7, 29.7, 26.2, 25.2, 23.0; MS-
(HR-ESI) m/z 320.2373 [M]+ (calcd 320.2378).
JHH ) 6.8 Hz, 6H), 1.22 (br d, JHH ) 6.8 Hz, 6H), 1.15 (d, JHH
)
6.8 Hz, 6H); 13C{1H} NMR (CDCl3) δ 155.5, 146.0, 145.8, 135.7,
132.2, 131.0, 129.9, 128.0, 125.3, 124.2, 123.8, 57.2, 29.0, 25.5,
24.4, 24.0, 23.6; MS(HR-ESI) m/z 405.3266 [M]+ (calcd 405.3264).
Synthesis of NHC,H+s 11a-d from 9a-d. Following the
procedure described for the synthesis of 4b, but heating at the
temperature and during time indicated hereafter, derivatives 11a-d
were isolated as white solids after washing with toluene and ether.
1
11a: 36 h at 135 °C; 83% yield; mp 204 °C; H NMR (CD3CN/
CDCl3, 20:1) δ 9.39 (s, 1H), 7.53 (m, 2H), 7.56 (m, 4H), 4.88 (m,
1H), 4.63 (t, JHH ) 11.8 Hz, 1H), 4.01 (dd, JHH ) 11.8, 10.2 Hz,
1H), 3.04 (m, 4H), 1.45 (d, JHH ) 6.5 Hz, 3H), 1.36 (m, 12H),
1.26-1.21 (m, 12H); 13C{1H} NMR (CD3CN/CDCl3, 20:1) δ 161.5,
148.4, 147.7, 147.6, 147.3, 132.4, 130.7, 128.7, 126.2, 126.0, 63.5,
61.2, 30.0, 29.9, 26.2, 25.6, 24.1, 24.0, 23.5, 18.5; MS(FAB) m/z
405 [M]+. 11b: 24 h at 110 °C; 80% yield; mp 212 °C; 1H NMR
(CD3CN) δ 10.45 (s, 1H), 7.58 (m, 2H), 7.43 (t, JHH ) 7.7 Hz,
4H), 4.23 (s, 2H), 3.16 (m, 4H), 1.59 (s, 6H), 1.46 (d, JHH ) 6.7
Hz, 12H), 1.40 (d, JHH ) 6.8 Hz, 6H), 1.30 (d, JHH ) 6.8 Hz, 6H);
13C{1H} NMR (CD3CN) δ 161.9, 149.9, 148.1, 132.8, 131.5, 127.5,
126.6, 126.4, 72.2, 67.0, 31.1, 30.6, 27.8, 27.4, 26.2, 24.4, 23.4;
MS(FAB) m/z 419 [M]+. 11c: 12 h at 135 °C; 78% yield; mp 166
1
°C; H NMR (CDCl3) δ 9.76 (s, 1H), 7.01 (s, 2H), 6.98 (s, 2H),
2.44 (s, 6H), 2.42 (s, 6H), 2.31 (s, 3H), 2.30 (s, 3H), 1.67 (s, 6H);
13C{1H} NMR (CDCl3) δ 159.4, 140.5, 140.3, 137.0, 135.0, 133.8,
130.6, 130.2, 127.4, 71.5, 64.0, 27.2, 21.2, 21.1, 20.1, 18.3; MS-
(FAB) m/z 335 [M]+. 11d: 12 h at 135 °C; 79% yield; mp 186
°C; 1H NMR (CD3CN) δ 9.54 (s, 1H), 7.70 (m, 1H), 7.59 (m 1H),
7.30 (m, 4H), 4.45 (s, 2H), 1.60 (s, 6H); 13C{1H} NMR (CD3CN)
δ 162.1, 160.2 (dd, JCF ) 249.7, 6.0 Hz), 158.1 (dd, JCF ) 248.2,
6.0 Hz), 134.8 (t, JCF ) 10.3 Hz), 132.9 (t, JCF ) 10.1 Hz), 114.0
(dd, JCF ) 7.4, 3.2 Hz), 113.8, (dd, JCF ) 6.8, 3.3 Hz), 72.9, 64.0,
25.4; MS(HR-ESI) m/z 323.1178 [M]+ (calcd 323.1171).
Synthesis of NHC,H+s 11a,b from 8a. A tube sealed by a
Teflon stopcock was loaded with 8a (2.00 g, 5.5 mmol), toluene
(20 mL), and 3-bromopropene (0.474 mL, 5.5 mmol) or 3-bromo-
2-methylpropene (0.54 mL, 5.5 mmol). Heating for 36 h at 135 °C
or 24 h at 110 °C afforded 11a and 11b, respectively, as white
solids after removal of the volatiles in vacuo and washing with
toluene. 11a: 1.76 g, 66%; mp 200 °C. 11b: 1.92 g, 70%; mp 204
°C.
Synthesis of Alkenylformamidines 9a-d. To a THF solution
(40 mL) of the corresponding formamidines 8 (5.5 mmol) at -78
°C was added a solution of n-BuLi in hexanes (5.5 mmol). The
mixture was stirred for 30 min and then was allowed to warm to rt
and stirred for a further 12 h. The mixture was again cooled to
-78 °C, and 3-bromopropene (5.5 mmol) or 3-bromo-2-methyl-
propene (5.5 mmol) was slowly added. The mixture was stirred
for 30 min at -78 °C and then heated at 50 °C for 12 h. Removal
of the volatiles under vacuum and extraction with hexanes afforded
derivatives 9a-d. Derivative 9a was obtained as a white solid
(94%): mp 62 °C; 1H NMR (CDCl3) δ 7.37-6.99 (m, 7H), 6.26-
6.13 (m, 1H), 5.19 (d, JHH ) 5.5 Hz, 1H), 5.15 (br s, 1H), 4.42 (d,
JHH ) 6.8 Hz, 2H), 3.33-3.18 (m, 4H), 1.30 (d, JHH ) 6.8 Hz,
6H), 1.22 (d, JHH ) 6.8 Hz, 12H), 1.15 (d, JHH ) 6.8 Hz, 6H);
13C{1H} NMR (CDCl3) δ 151.1, 148.4, 147.5, 140.1, 138.4, 133.4,
128.9, 124.4, 122.8, 118.3, 53.0, 28.5, 28.0, 25.4, 24.4, 23.8; MS-
(EI) m/z 405 [M + H]+. Derivative 9b was obtained as a white
1
solid (89%): mp 73 °C; H NMR (CDCl3) δ 7.34-6.96 (m, 7H),
4.84 (s, 1H), 4.68 (s, 1H), 4.41 (s, 2H), 3.24 (m, 4H), 1.98 (s, 3H),
1.29 (d, JHH ) 6.7 Hz, 6H), 1.20 (d, JHH ) 6.8 Hz, 12H), 1.12 (d,
JHH ) 6.8 Hz, 6H); 13C{1H} NMR (CDCl3) δ 152.2, 148.4, 147.5,
141.5, 140.0, 138.7, 128.7, 124.4, 122.8, 115.8, 55.3, 28.4, 28.0,
25.6, 24.5, 23.8, 21.9; MS(EI) m/z: 419 [M + H]+. Derivative 9c
was obtained as a white solid (91%): mp 72 °C; 1H NMR (C6D6)
δ 6.91 (br s, 2H), 6.80 (br s, 1H), 6.69 (br s, 2H), 4.77 (br s, 2H),
4.36 (br s, 2H), 2.28 (s, 10H), 2.09 (s, 8H), 1.98 (s, 3H); 13C{1H}
NMR (C6D6) δ 153.4, 148.8, 143.4, 140.6, 137.6, 137.4, 131.2,
130.0, 129.4, 115.1, 54.2, 22.6, 21.3, 21.2, 19.7, 18.8; MS(EI) m/z
335 [M + H]+. Derivative 9d was obtained as a yellow oil (92%):
1H NMR (CDCl3) δ 7.89 (m, 1H), 7.26 (m, 1H), 7.00 (m, 2H),
6.87 (m, 3H), 4.87 (s, 1H), 4.81 (s, 1H), 4.63 (s, 2H), 1.82 (s, 3H);
Synthesis of 13. Following the procedure for 9a, amidine 1221
(1.17 g, 2.7 mmol) was converted to its corresponding alkenyl
derivative using 1 equiv of n-BuLi and 3-bromo-2-methylpropene.
The alkenylamidine was obtained as a white solid (1.25 g, 95%):
mp 90 °C; 1H NMR (CDCl3) δ 7.42-6.84 (m, 11H), 5.25 (s, 1H),
4.98 (s, 1H), 4.39 (s, 2H), 3.69 (sept, JHH ) 6.6 Hz, 2H), 3.17
(sept, JHH ) 6.6 Hz, 2H), 1.90 (s, 3H), 1.26 (d, JHH ) 6.6 Hz, 6H),
1.19 (2 × overlapping d, JHH ) 6.6 Hz, 12H), 0.98 (d, JHH ) 6.6
Hz, 6H); 13C{1H} NMR (CDCl3) δ 156.7, 147.5, 145.4, 142.0,
141.4, 138.0, 133.6, 128.9, 128.4, 128.0, 127.0, 124.4, 122.6, 121.7,
110.5, 58.6, 28.5, 28.4, 26.6, 24.8, 23.2, 22.3, 22.0; MS(FAB) m/z
495 [M + H]+. Following the procedure described for the synthesis
1
of 4b, 13 was obtained from 12 in 85% yield: mp 181 °C; H
(20) Chen, C. L.; Liu, Y. H.; Peng, S. M.; Liu, S. T. J. Organomet.
Chem. 2004, 689, 1806-1815.
(21) Bambirra, S.; van Leusen, D.; Meetsma, A.; Hessen, B.; Teuben,
J.H. Chem. Commun. 2003, 522-523.
J. Org. Chem, Vol. 72, No. 9, 2007 3497

Jazzar et al.
1
NMR (CDCl3) δ 7.40-7.24 (m, 3H), 7.17-7.03 (m, 6H), 6.92 (m,
2H), 4.45 (s, 2H), 2.83 (sept, JHH ) 6.6 Hz, 4H), 1.71 (s, 6H),
1.27 (d, JHH ) 6.6 Hz, 6H), 1.25 (d, JHH ) 6.6 Hz, 6H), 0.86 (d,
JHH ) 6.6 Hz, 6H), 0.70 (d, JHH ) 6.6 Hz, 6H); 13C{1H} NMR
(CDCl3) δ 165.8, 147.0, 144.8, 134.3, 131.4, 131.2, 129.5, 128.8,
127.9, 126.2, 125.5, 121.5, 70.9, 66.5, 29.4, 29.1, 26.3, 25.6, 25.1,
24.5, 23.1; MS(FAB) m/z 495 [M]+.
°C; H NMR (CDCl3) δ 7.83 (dd, JHH ) 1.9, 7.4 Hz, 1H), 7.48-
7.21 (m, 6H), 5.30 (s, 1H), 5.16 (s, 1H), 3.21 (sept, JHH ) 6.8 Hz,
2H), 2.24 (s, 3H), 1.25 (d, JHH ) 6.8 Hz, 12H); 13C{1H} NMR
(CDCl3) δ 168.5, 146.8, 146.5, 142.5, 134.3, 131.2, 130.6, 129.2,
128.8, 128.6, 127.7, 123.8, 116.1, 29.0, 25.4, 24.0; MS(EI) m/z
322 [M + H]+. 16b: 1.93 g, 87% yield; 1H NMR (CDCl3) δ 7.66
(dd, JHH ) 1.8, 7.2 Hz, 1H), 7.36 (m, 2H), 7.20 (dd, JHH ) 1.5, 7.2
Hz, 1H), 6.00 (bs, 1H), 5.24 (s, 1H), 5.10 (s, 1H), 2.12 (s, 3H),
1.44 (s, 9H); 13C{1H} NMR (CDCl3) δ 168.0, 146.0, 141.1, 135.0,
130.2, 129.0, 128.7, 127.7, 115.9, 51.8, 28.7, 24.7.
Synthesis of Alkenylurea 14. To a solution of lithium (2,6-
diisopropylphenyl)amide22 (1.5 g, 8.2 mmol) in Et2O (20 mL) at rt
was added dropwise 3-bromo-2-methylpropene (0.91 mL, 1.22 g,
9.0 mmol). The solution was stirred for 2 h, and then the volatiles
were removed under vacuum and the residue was extracted with
hexanes and filtered. Removal of volatiles from the filtrate under
vacuum provided (2,6-diisopropylphenyl)(2-methylallyl)amine as
Synthesis of Cyclic C-Chloro Iminium Salt 17a,b. Following
the procedure used for 15 and heating as indicated hereafter, 17a,b
were obtained as off-white solids. 17a: 80 °C for 24 h, 86% yield;
mp 130 °C; 1H NMR (CD3CN) δ 9.49 (d, JHH ) 7.9 Hz, 1H), 7.95
(t, JHH ) 7.6 Hz, 1H), 7.76 (m, 2H), 7.48 (t, JHH ) 7.7 Hz, 1H),
7.36 (d, JHH ) 7.9 Hz, 2H), 3.08 (sept, JHH ) 6.8 Hz, 2H), 1.72 (s,
6H), 1.24 (d, JHH ) 6.8 Hz, 6H), 1.16 (d, JHH ) 6.8 Hz, 6H); 13C-
{1H} NMR (CDCl3) δ 171.6, 155.2, 145.6, 138.0, 131.2, 130.8,
129.2, 125.2, 123.9, 122.6, 100.4, 29.7, 26.7, 24.3, 23.6. MS-
(HR-ESI) m/z 322.2174 [M - Cl + OH]+ (calcd 322.2170). 17b:
80 °C for 24 h, 78% yield; mp 154 °C; H NMR (CDCl3) δ 9.77
(d, JHH ) 7.9 Hz, 1H), 7.76 (t, JHH ) 7.5 Hz, 1H), 7.64 (t, JHH
7.7 Hz, 1H), 7.39 (d, JHH ) 7.7 Hz, 1H), 1.79 (s, 6H), 1.67 (s,
9H); 13C{1H} NMR (CDCl3) δ 170.3, 152.1, 136.2, 130.4, 130.0,
120.4, 120.4, 98.4, 58.3, 28.5, 26.9; MS(HR-ESI) m/z 218.1543
[M - Cl + OH]+ (calcd 218.1539).
Palladium Complex 18a. A CH2Cl2 (15 mL) solution of 17a
(0.10 g, 0.27 mmol) and tetrakis(triphenylphosphine)palladium (0.31
g, 0.27 mmol) was heated under reflux for 24 h. The solvent was
removed under vacuum, then repeated extraction with boiling
hexane to remove the liberated triphenylphosphine provided
complex 18a as a yellow solid (0.11 g, 55%): 1H NMR (CDCl3)
δ 7.67-7.19 (m, 22H), 3.09 (sept, JHH ) 6.9 Hz, 2H), 1.61 (s,
6H), 1.21 (d, JHH ) 6.5 Hz, 12H); 13C{1H} NMR (CDCl3) δ 227.1
(d, JPC ) 175 Hz), 149.1 (br), 148.1, 134.8 (d, JPC ) 11.0 Hz),
133.7, 132.9, 130.6 (d, JPC ) 40.5 Hz), 130.1, 129.7, 128.6, 128.0
(d, JPC ) 9.9 Hz), 125.7, 120.0, 84.3 (d, JPC ) 7.9 Hz), 29.5, 29.0,
26.5, 24.4; 13C NMR resonances corresponding to the aromatic
quaternary carbons of the fused ring system could not be located;
31P NMR (CD3CN) δ +15.3; MS(HR-ESI) m/z 778.1141 [M +
Cl]+ (calcd 778.1155).
1
a colorless liquid: yield (1.71 g, 90%); H NMR (CDCl3) δ 7.12
(m, 3H), 5.15 (s, 1H), 4.94 (s, 1H), 3.42 (d, JHH ) 7.6 Hz, 2H),
3.29 (sept, JHH ) 6.8 Hz, 2H), 2.97 (br t, JHH ) 7.4 Hz, 1H), 1.89
(s, 3H), 1.27 (d, JHH ) 6.8 Hz, 12H). 13C NMR (neat) δ 144.1,
143.3, 142.6, 124.2, 123.4, 110.8, 58.1, 27.7, 24.3, 20.8.
A solution of n-BuLi in hexanes (5.4 mL, 1.6M, 8.6 mmol) was
added to an Et2O solution (40 mL) of (2,6-diisopropylphenyl)(2-
methylallyl)amine (2.00 g, 8.6 mmol) at -78 °C. After 30 min,
the mixture was warmed to rt and stirred for 3 h. The mixture was
then cooled to -78 °C, and 2,6-diisopropylphenyl isocyanate (1.85
mL, 8.6 mmol) was added dropwise. The mixture was warmed to
rt and stirred for 12 h, over which time a white precipitate formed.
The mixture was cooled in an ice bath, and H2O (40 mL) was added
slowly. Extraction with Et2O, drying over MgSO4, and removal of
the volatiles under vacuum afforded 14 as an off-white crystalline
solid (3.34 g, 89%): mp 147 °C; 1H NMR (CDCl3) δ 7.38 (t, JHH
) 7.4 Hz, 1H), 7.27 (d, JHH ) 7.4 Hz, 2H), 7.21 (t, JHH ) 7.4 Hz,
1H), 7.12 (d, JHH ) 7.4 Hz, 2H), 5.40 (s, 1H), 4.81 (s, 1H), 4.70
(s, 1H), 4.22 (s, 2H), 3.30 (sept, JHH ) 6.8 Hz, 2H), 3.13 (sept,
JHH ) 6.8 Hz, 2H), 1.93 (s, 3H), 1.31 (d, JHH ) 6.8 Hz, 6H), 1.28
(d, JHH ) 6.8 Hz, 6H), 1.17 (d, JHH ) 6.8 Hz, 12H); 13C{1H} NMR
(CDCl3) δ 156.8, 148.5, 146.8, 142.9, 136.8, 132.0, 129.3, 127.8,
125.3, 123.5, 114.2, 57.3, 28.6, 26.2, 24.6, 24.2, 21.2.
Synthesis of C-chloro Imidazolinium Salt 15. To a toluene
solution (10 mL) of alkenylurea 14 (1.00 g, 2.3 mmol) in a sealable
tube fitted with a Teflon stopcock at -78 °C was added a toluene
solution of phosgene (1.26 mL, 2.0 M, 2.5 mmol). After 10 min at
-78 °C, the mixture was warmed to rt and stirred for 2 h. The
mixture was then sealed and heated at 80 °C for 24 h. After removal
of the volatiles in vacuo and precipitation of the product from Et2O
(20 mL), 15 was obtained as a white solid (0.78 g, 78%): mp 142
°C; 1H NMR (CDCl3) δ 7.48 (t, JHH ) 7.7 Hz, 1H), 7.29 (m, 3H),
7.12 (d, JHH ) 7.7 Hz, 2H), 3.90 (s, 2H), 2.99 (sept, JHH ) 6.8 Hz,
4H), 1.66 (s, 6H), 1.48 (d, JHH ) 6.8 Hz, 6H), 1.31 (d, JHH ) 6.8
Hz, 6H), 1.20 (d, JHH ) 6.8 Hz, 6H), 1.14 (d, JHH ) 6.8 Hz, 6H);
13C{1H} NMR (CDCl3) δ 158.2, 148.6, 145.8, 132.0, 129.4, 126.6,
125.7, 123.8, 88.7, 64.1, 29.4, 28.8, 27.7, 25.7, 24.2, 23.8; MS-
(FAB) m/z 435 [M- Cl + (OH)]+.
1
)
Labeling Experiment: Synthesis of Cyclic Iminium Salt 4cD.
In a sealable vessel fitted with a Teflon stopcock was bubbled
deuterium chloride gas through a solution of alkenyl imine 2c (0.34
g, 1.0 mmol) in toluene for 1 min. The vessel was then sealed and
heated to 110 °C for 16 h. After the mixture was cooled to rt, the
volatiles were remove under vacuum and the residue was extracted
with CD3CN and transferred to an NMR tube: 1H NMR (CD3CN)
δ 9.85 (s, 1H, CHdN), 7.57 (t, JHH ) 7.79 Hz, 1H, Har), 7.43 (m,
2H, Har), 4.69 (m, 1H, N-CH), 2.81-2.57 (m, 3H, 2H from CHi-Pr
plus 1H from endocyclic CH2), 2.07-1.92 (m, 3H, includes 1H
from endocyclic CH2), 1.81 (m, 4H), 1.67-1.46 (m, 5H, includes
CHDEt), 1.30-1.16 (4 overlapping d, 12H, CH3iPr), 0.85 (d, JHH
)
Synthesis of Alkenylamides 16a,b. A solution of n-BuLi in
hexanes (6.3 mL, 1.6 M, 10.2 mmol) was added to an Et2O solution
(20 mL) of 1-bromo-2-isopropenylbenzene23 (2.00 g, 10.2 mmol)
at -78 °C. After 30 min, the mixture was warmed to rt and stirred
for an additional 1 h. The mixture was then cooled to -78 °C, and
2,6-diisopropylphenylisocyanate (2.17 mL, 10.2 mmol) or tert-butyl
isocyanate (1.17 mL, 10.2 mmol) was slowly added. The mixture
was allowed to warm to rt and stirred for 12 h while a white
precipitate formed. After the mixture was cooled with an ice bath,
H2O (20 mL) was added slowly. Extraction with Et2O, drying over
MgSO4, and removal of the volatiles under vacuum afforded 16a,b
as off-white crystalline solids. 16a: 2.66 g, 81% yield; mp 115
6.48 Hz, 3H, CH3-Et); 2H NMR (CD3CN) δ 10.49 (br, DCl2
counterion), 1.60 (br, CHDEt); 13C{1H} NMR (CD3CN) δ 192.8
(NdCH), 144.6, 143.4 (Carïrthï-DIPP), 132.4 (Carpara-DIPP), 131.5
(Caripsï-DIPP), 125.8, 125.7 (Carmeta-DIPP), 78.1 (N-CH), 54.4 (C),
38.0 (endocyclic NCHCH2), 34.2, 31.7, 26.2 (t, JCD ) 19.3 Hz,
CHDEt), 25.2, 22.1, 21.6 (CH2), 29.4, 29.3 (CHi-Pr), 25.6, 25.0,
23.4, 22.6 (CH3i-Pr), 10.7 (CH3Et). Assignments for the aliphatic
region of the 1H and 13C NMR spectrum were made based on 1H-
-
Et
1H and 1H-13C coupling correlations of the N-CH and CH3
protons from COSY and HMBC spectra, in addition to DEPT-135°
and DEPT-90° protocols; MS(FAB) m/z 326 [M]+.
Crystal Structure Determination of Compounds 4b, 10a, 11a,
and 18a. The Bruker X8-APEX X-ray diffraction instrument with
Mo radiation was used for data collection. All data frames were
collected at low temperature (T ) 100 K) using an ω,æ-scan mode
(0.5° ω-scan width, hemisphere of reflections) and integrated using
(22) Berreau, L. M.; Chen, J.; Woo, L. K. Inorg. Chem. 2005, 44, 7304-
7306.
(23) Fleming, I.; Woolias, M. J. Chem. Soc., Perkin Trans. 1 1979, 3,
829-837.
3498 J. Org. Chem., Vol. 72, No. 9, 2007

Intramolecular “Hydroiminiumation and -amidiniumation” of Alkenes
a Bruker SAINTPLUS software package. The intensity data were
corrected for Lorentzian polarization. Absorption corrections were
performed using the SADABS program. The SIR97 software
package was used for direct methods of phase determination and
the Bruker SHELXTL software package for structure refinement
and difference Fourier maps. Atomic coordinates and isotropic and
anisotropic displacement parameters of all of the non-hydrogen
atoms of two compounds were refined by means of a full-matrix
least-squares procedure on F2. All H-atoms were included in the
refinement in calculated positions riding on the C atoms. Drawings
of molecules were performed using Ortep 3.
Crystal and structure parameters of 4b: size 0.51 × 0.17 ×
0.12 mm3, monoclinic, space group P2(1)2(1)2(1), a ) 10.5761-
(7) Å, b ) 16.3822(10) Å, c ) 19.6147(12) Å, R ) γ ) â )
90.0°, V ) 3398.4(4) Å3, Fcalcd ) 1.256 g/cm3, Mo radiation (λ )
0.71073 Å), T ) 100(2) K, reflections collected ) 67338,
independent reflections ) 13087 (Rint ) 0.0797), absorption
coefficient µ ) 0.602 mm-1, max/min transmission ) 0.9313 and
0.7488, 387 parameters were refined and converged at R1 ) 0.0381,
wR2 ) 0.0744, with intensity I > 2σ(I).
Crystal and structure parameters of 10a: size 0.40 × 0.15 ×
0.10 mm3, monoclinic, space group P2(1)/c, a ) 20.6299(18) Å, b
) 19.1236(17) Å, c ) 13.9795(12) Å, R ) 90.0°, â ) 108.2590-
(10)°, γ ) 90.0°, V ) 5237.5(8) Å3, Fcalcd ) 1.199 g/cm3, Mo
radiation (λ ) 0.71073 Å), T ) 100(2) K, reflections collected )
24727, independent reflections ) 6333 (Rint ) 0.0322), absorption
coefficient µ ) 0.163 mm-1, max/min transmission ) 0.9839 and
0.9378, 576 parameters were refined and converged at R1 ) 0.0587,
wR2 ) 0.1462, with intensity I > 2σ(I).
Crystal and structure parameters of 11a: size 0.46 × 0.14 ×
0.06 mm3, monoclinic, space group P2(1)/c, a ) 17.326(2) Å, b )
8.5078(10) Å, c ) 21.213(3) Å, R ) γ ) 90.0°, â ) 101.369(2)°,
V ) 3065.6(6) Å3, Fcalcd ) 1.212 g/cm3, Mo-radiation (λ ) 0.71073
Å), T ) 100(2) K, reflections collected ) 17060, independent
reflections ) 4376 (Rint ) 0.0358), absorption coefficient µ ) 0.406
mm-1, max/min transmission ) 0.9780 and 0.8369, 363 parameters
were refined and converged at R1 ) 0.0553, wR2 ) 0.1451, with
intensity I > 2σ(I).
Crystal and structure parameters of 18a: size 0.70 × 0.19 ×
0.13 mm3, monoclinic, space group P2(1)/c, a ) 12.535(3) Å, b )
20.342(5) Å, c ) 27.860(7) Å, R ) 90.0°, â ) 94.939(6)°, γ )
90.0°, V ) 7077(3) Å3, Fcalcd ) 1.398 g/cm3, Mo radiation (λ )
0.71073 Å), T ) 100(2) K, reflections collected ) 32838,
independent reflections ) 10046 (Rint ) 0.0754), absorption
coefficient µ ) 0.750 mm-1, max/min transmission ) 0.9088 and
0.6219, 823 parameters were refined and converged at R1 ) 0.0538,
wR2 ) 0.1277, with intensity I > 2σ(I).
Acknowledgment. We are grateful to the NIH (R01 GM
68825) and RHODIA for financial support.
Supporting Information Available: X-ray crystallographic data
for 4b, 10a, 11a, and 18a (CIF) and spectral data for prepared
compounds. This material is available free of charge via the Internet
at http://pubs.acs.org.
JO0703909
J. Org. Chem, Vol. 72, No. 9, 2007 3499