Cyclisation versus 1,1-carboboration: Reactions of B(c6f 5)3 with propargyl amides

Article abstract of DOI:10.1002/chem.201301899

A series of propargyl amides were prepared and their reactions with the Lewis acidic compound B(C₆F₅)₃ were investigated. These reactions were shown to afford novel heterocycles under mild conditions. The reaction of a variety of N-substituted propargyl amides with B(C₆F₅)₃ led to an intramolecular oxo-boration cyclisation reaction, which afforded the 5-alkylidene-4,5-dihydrooxazolium borate species. Secondary propargyl amides gave oxazoles in B(C ₆F₅)₃ mediated (catalytic) cyclisation reactions. In the special case of disubstitution adjacent to the nitrogen atom, 1,1-carboboration is favoured as a result of the increased steric hindrance (1,3-allylic strain) in the 5-alkylidene-4,5-dihydrooxazolium borate species. Copyright

Full text of DOI:10.1002/chem.201301899

DOI: 10.1002/chem.201301899
Cyclisation versus 1,1-Carboboration: Reactions of B
Amides
ACHTNUGTRNE(NNUG C6F5)3 with Propargyl
Rebecca L. Melen,[a] Max M. Hansmann,[a, b] Alan J. Lough,[a]
A. Stephen K. Hashmi,[b] and Douglas W. Stephan*[a]
Abstract: A series of propargyl amides
were prepared and their reactions with
the Lewis acidic compound B(C6F5)3
were investigated. These reactions
were shown to afford novel heterocy-
cles under mild conditions. The reac-
tion of a variety of N-substituted pro-
reaction, which afforded the 5-alkyli-
dene-4,5-dihydrooxazolium borate spe-
cies. Secondary propargyl amides gave
ic) cyclisation reactions. In the special
case of disubstitution adjacent to the
nitrogen atom, 1,1-carboboration is
favoured as a result of the increased
steric hindrance (1,3-allylic strain) in
the 5-alkylidene-4,5-dihydrooxazolium
borate species.
AHCTUNGTRENNUNG
oxazoles in BACTHNGUTERN(NUG C6F5)3 mediated (catalyt-
Keywords: 1,1-carboboration · al-
kynes · boron · cyclization · oxa-
zoles · propargyl amides
ACHTUNGTRENNUNGpargyl amides with BCAHUTNGTRNEN(UGN C6F5)3 led to an
intramolecular oxo-boration cyclisation
Introduction
catalysts incorporating the coinage metals and platinum
group elements, namely palladium,[5] silver[6] and gold.[7]
Boron-based reagents incorporating alkyl, vinyl and al-
kynyl boranes or borates are well established and important
in a variety of organic transformations[8] including cross-cou-
pling or transition-metal-catalysed addition reactions. More
recently, the unveiling of frustrated Lewis pair (FLP)[9] reac-
tivity has furthered the utility of B-reagents in stoichiomet-
ric and catalytic synthetic chemistry. Among the numerous
small-molecule activation[10] reactions explored in FLP
chemistry to date, the interaction of FLPs with alkynes[11]
has been shown to proceed either to give 1,2-addition prod-
ucts or effect deprotonation of terminal alkynes affording
ꢀ ꢁ ꢀ
The cyclisation reactions of propargyl amides to the corre-
sponding methylene-oxazolines and oxazoles (Scheme 1)
Scheme 1. Cyclisation of propargyl amides to oxazoles via methylene-ox-
azolines.
offer synthetic routes to heterocycles that occur in many
natural products, drug and pharmaceutical molecules.[1] In
particular these molecular fragments are found in anti-bac-
terials, herpes simplex virus type 1 (HSV-1) inhibitors,
serine threonine phosphate inhibitors, antitumor agents and
antifungal agents.[1c, 2] Additionally, oxazolines and oxazoles
are important intermediates and reagents in organic synthe-
sis, can be used as ligands[3] and act as protecting groups.[4]
Such cyclisations are typically effected by transition-metal
(C6F5)3] (Scheme 2).[11]
salts of the form [R3PH]ACTHNGURTENNU[G R C C BCAHTUNGTRENNNUG
In general, more basic donors favoured the latter pathway,
and thus use of amine donors in these FLP reactions with al-
kynes typically gave deprotonation except in the case of in-
tramolecular ring closures.[12] In related chemistry, strongly
electrophilic boron reagents have also been shown to react
with alkynes on their own, yielding 1,1-carboboration prod-
uct mixtures of
E and Z isomers of vinyl boranes
(Scheme 2).[13]
[a] Dr. R. L. Melen,+ M. M. Hansmann,+ Dr. A. J. Lough,++
Prof. Dr. D. W. Stephan
Department of Chemistry, University of Toronto
80 St. George Street, Toronto, ON, M5S 3H6 (Canada)
E-mail: dstephan@chem.utoronto.ca
[b] M. M. Hansmann,+ Prof. Dr. A. S. K. Hashmi
Organisch-Chemisches Institut
Ruprecht-Karls-Universitꢀt Heidelberg
Im Neuenheimer Feld 270, 69120 Heidelberg (Germany)
[+] These authors equally contributed to this paper.
++] Crystallographic investigation.
[
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/chem.201301899.
Scheme 2. Reactivity of FLPs and BACTHNUTRGNE(UNG C6F5)3 with terminal alkynes.
11928
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FULL PAPER
The only metal-free method to induce cyclisations yield-
ing oxazolines and oxazoles requires the use of harshly basic
2a,c,14]
conditions.[1c,
Given the reactivity of electrophilic bo-
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
moted cyclisation reactions of propargyl amides under mild
conditions, which afford a broad range of dihydrooxazolium
borate species. Further work demonstrates the impact of
steric effects, indicating that congestion can prompt catalysis
or promote an alternative reaction pathway involving
1,1-carboboration.
Results and Discussion
N-Substituted propargyl amides are ideal starting materials
to probe the reactivity of amide and alkyne functionalities
with the Lewis acid BACTHNUTRGNEUNG(C6F5)3. These starting materials are
also incapable of aromatisation to the corresponding oxa-
zole and are readily accessible in high yields by the reaction
of the corresponding propargyl amine with an acyl chloride
in the presence of a base using known procedures.[7,16–22]
Thus, the 1:1 reaction of BACHTUNRGTNE(UNG C6F5)3 with a series of N-substi-
tuted propargyl amides and formamides bearing a variety of
functional groups on the benzene ring was monitored in situ
by multinuclear NMR (1H, 11B and 19F) spectroscopy
(Scheme 3).
Figure 1. POV-ray depictions of the molecular structure of 2c (top) and
2i (bottom).
the emergence of a very sharp singlet at dꢂꢀ16 ppm in the
11B NMR spectrum and the disappearance of the peak at
d=0 ppm (Figure 2). This was attributed to the formation of
ꢀ
a B C bond, based on similar chemical shifts previously re-
ported by Stephan and Erker et al.[12] The products formed
in these reactions were found to be the 5-alkylidene-4,5-di-
hydrooxazolium borates 3a–h (Scheme 4). These assign-
ments were confirmed both spectroscopically and by X-ray
crystallography (Figure 3). These products are formed by a
5-exo-oxo-boration cyclisation reaction (Scheme 4). In all
cases these reactions showed exclusive Markovnikov and
Z-selectivity. The formation of these products infers an equi-
Scheme 3. Reaction of B
propargyl formamides.
ACHTNUGERTN(NGNU C6F5)3 with various a) propargyl amides and b)
In all cases the first species detected was the expected
adduct afforded by coordination of the Lewis basic amide to
the Lewis acidic BACHTUNGTRENNUNG(C6F5)3. This boron–oxygen coordination
was reflected in the 11B NMR spectra by the presence of a
broad peak around d=0 ppm. In the case of the reaction of
N-methyl-N-(prop-2-yn-1-yl)toluamide (1c) with BACHTUNRGTNEUNG(C6F5)3 in
[D8]toluene, colourless needle-shaped crystals of 2c were
obtained in 83% yield after 4 h at 458C. Similarly, the reac-
tion of N-phenyl-N-(prop-2-yn-1-yl)formamide (1i) with
BACHTUNGTRENNUNG(C6F5)3 afforded colourless crystals of the adduct 2i after
four days at 458C. In both of these cases, the structures of
the products were confirmed by X-ray diffraction (Figure 1).
Subsequent heating of the 1:1 reaction mixtures of
Figure 2. In situ 11B NMR spectra at various time intervals of the reaction
B
G
of 1 f with BACTHUNGTERN(NUG C6F5)3 in [D8]toluene at 458C.
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D. W. Stephan et al.
AHCTUNGTRENNUNG
acid AlACHTUNRGTNE(UNG C6F5)3 were probed. In
these cases, either no reaction
occurred or the results proved
inconclusive as a variety of
products was obtained as evi-
denced by NMR spectroscopy.
ꢀ
The reactions of N H-sub-
stituted propargyl amides with
BACHTNUTRGNEUNG(C6F5)3 were also explored.
These reactions initially afford-
ed the 5-alkylidene-4,5-dihy-
drooxazolium borate species
3k–3q, which were isolated
(Scheme 5). The yields based
on in situ NMR spectroscopy
are all consistently high, but
the isolated yields in some
cases were lowered as a result
Scheme 4. Cyclised products from the reactions of propargyl amides with B
ed.
ACHTNUGTERN(NGNU C6F5)3, isolated yields are indicat-
librium involving borane interaction with the alkyne fol-
lowed by nucleophilic attack of the activated alkyne by the
carbonyl–oxygen atom. The Z-configured products are con-
sistent with this view, as a concerted oxo-boration cyclisation
mechanism would be expected to give an E-configured ole-
finic fragment. In the case of 3b, 3d, 3e, 3g and 3h single-
crystal X-ray crystallography confirmed the nature of the
zwitterionic dihydrooxazolium borate products (Figure 3).
The metric parameters of the essentially planar dihydrooxa-
zolium rings were very similar.
Although these reactions are relatively slow at room tem-
perature, they were accelerated upon heating to 458C or by
performing the reaction in polar solvents such as CD2Cl2 or
[D8]THF. Nonetheless, [D8]toluene is the preferred solvent
as the reactions proceeded more cleanly; use of polar sol-
vents or temperatures above 458C resulted in minor by-
products such as those arising from the 1,1-carboboration
pathway suggested by 19F NMR spectroscopy (vide infra).
The rate of these reactions appeared empirically to be de-
pendent upon the nature of the substituent on the aromatic
ring and followed the order p-NO2 > p-H> p-OMe. This
suggests that electron-withdrawing substituents (which de-
crease the basicity of the amide-oxygen atom), promote dis-
sociation of the Lewis acid in the rate-determining step, al-
lowing the Lewis acid to activate the alkyne thus affording
cyclisation (Scheme 4). This view is further supported by the
observation that attempts to effect the cyclisation of 2i or 2j
proved unsuccessful, even upon heating to 458C for two
days. The lack of reactivity of 2i and 2j is attributable to the
Scheme 5. Products from substrates with N-H substituted propargyl
amides; isolated yields are indicated.
of incomplete crystallisation. In the case of 3o and 3p, these
products were crystallographically characterised (Figure 4).
In comparison to the cyclisation experiments with the
ꢀ
N-substituted propargyl amides, the N H compounds
formed more rapidly and consequently could be prepared at
room temperature. It is noteworthy that related derivatives
can be prepared by using transition-metal catalysts.[5–7] In
ꢀ
these cases, the N H proton migrates to the vinyl fragment,
ꢀ
stronger B O bond, which disfavours dissociation. In addi-
affording oxazoles. In the case of gold catalysts, this has
been shown to proceed by anti-oxyauration followed by
proto-deauration to afford the 5-alkylidene-4,5-dihydrooxa-
zole and subsequent isomerisation to produce the oxazole.[7]
It is also interesting to highlight that in the case of the tran-
sition metals it is a challenging task to capture the corre-
sponding vinyl-transition-metal compounds. For example,
ꢀ
tion, the generation of a cationic charge on the N=C O
moiety from cyclisation would also disfavour cyclisation. In
the cases of 1a–h the aromatic substituent at R1 stabilises
the benzylic cationic charge by conjugation.
Variation in the Lewis acid was also investigated. Reac-
tion of 1c with BPh3, (C6F5)2BCl, Mes2BF, 9-BBNCl, HB-
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Reactions of BACHTUNGTRENNUNG(C6F5)3 with Propargyl Amides
FULL PAPER
Figure 4. POV-ray depictions of the molecular structure of 3o (top) and
3p (bottom).
prone towards protonation and thus these may be of interest
for use in organic synthesis.
The corresponding reaction of 4-methyl-N-(prop-2-yn-1-
1
yl)benzamide 1l with B
N
11B and 19F NMR spectroscopy. At room temperature, the
11B NMR data in [D8]toluene initially showed a peak at d=
0.6 ppm after 6 h due to the Lewis acid/base adduct 2l,
which subsequently isomerised to give the cyclised product
3l, as revealed by a new resonance at d=ꢀ16.3 ppm (ca.
60% conversion). Performing the reaction at higher temper-
atures (458C) resulted in the formation of a new species
(4l) (Scheme 5), which gave a signal at d=ꢀ6.8 ppm in the
1
11B NMR spectrum. H, 11B and 19F NMR spectroscopy sug-
gested the formulation of 4l as the borane adduct of the cor-
responding oxazole (Scheme 5). This assignment was con-
firmed by the independent synthesis of the oxazole 5l[7] and
the combination with BACHTUNRGTNE(NUG C6F5)3, which yielded the adduct
with identical NMR spectral parameters to 4l. Subsequently,
the formulation of 4l was further confirmed by an X-ray
crystallographic study (Figure 5). In related reactions, heat-
ing the compounds 3k, 3m and 3n to 608C in [D8]THF, af-
forded the analogous borane adducts of the corresponding
Figure 3. POV-ray depictions of the molecular structure of 3b, 3d, 3e, 3g
and 3h (from top to bottom).
1
oxazoles 4k, 4m and 4n in high yield, as observed by H,
11B and 19F NMR spectroscopy.[15] This demonstrates that
migration of the proton from nitrogen to effect protonation
ꢀ
ꢀ
fast protodeauration of the C Au bond can only be sup-
of the C B bond prompts formation of the aromatic
oxazole.
pressed by addition of an external sterically bulky base.[7e]
In contrast, for the formation of the present species, the
Efforts to exploit this chemistry for the catalytic synthesis
of oxazoles were unsuccessful, inferring that the N!B
ꢀ
C B bonds in the vinyl boron products 3 are much less
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D. W. Stephan et al.
Figure 5. POV-ray depictions of the molecular structure of 4l.
Figure 6. POV-ray depictions of the molecular structure of 7r.
dative bond in the product is too strong to release BACHTNUTRGNEUNG(C6F5)3
precluding its role as a catalyst. To overcome this issue a de-
rivative bearing a more bulky adamantyl substituent (1o) at
R1 was employed, as this should sterically frustrate the
dative N!B bond in the borane–oxazole adduct. This
proved to be a suitable strategy as 1o is catalytically con-
ring. This stands in stark contrast to previous studies where
mixtures of E and Z isomers were observed even in the
presence of intramolecular coordination.[13] Monitoring the
reaction by NMR spectroscopy reveals the initial but transi-
ent formation of 3r. However, this cyclisation is apparently
reversible as this is consumed in the formation of the 1,1-
carboboration product 7r. This may result from increased
verted to the oxazole using 10 mol% BACHTNURGTNEUNG(C6F5)3 in 83% yield
after 10 days at 1008C. While this is slow, this finding does
demonstrate the concept that propargyl amides can be cata-
lytically cyclised without the participation of a transition-
metal catalyst.
It was further envisaged that the additional steric bulk of
the propargyl amide 1r would facilitate catalytic cyclisation.
In this case the formation of the oxazole would not be possi-
ble but rather an alkylideneoxazoline (6r, Scheme 6) would
steric hindrance from the gem-CMe2 group and BACHTUNGTRENNUNG(C6F5)3
which lie cis to each other in the cyclised intermediate, lead-
ing to 1,3-allylic strain which disfavours the cyclisation
event. Further evidence for the transient nature of 3r is the
observation of the minor byproduct, the alkylideneoxazoline
6r by 1H NMR spectroscopy (Scheme 6).
Conclusion
In conclusion, our study has demonstrated that Lewis acidic
BACHTUNRTGNEUNG(C6F5)3 can promote the intramolecular cyclisations of a
broad range of propargyl amides by an anti oxo-boration
mechanism affording zwitterionic 5-alkylidene-4,5-dihy-
drooxazolium borate species. This reaction was shown to be
highly Z-selective even in the presence of a variety of func-
ꢀ
tional groups. Furthermore, reactions of the N H propargyl
amides also proceed via 5-alkylidene-4,5-dihydrooxazolium
borate intermediates, undergoing rearrangement to form ox-
azoles in which B
gen atom. Bulky substituents such as an adamantyl group
allow the reaction to become catalytic in B(C6F5)3 due to
ACHTNUGRTNE(NGNU C6F5)3 is coordinated to the oxazole nitro-
Scheme 6. Reactions pathways of 2r affording 7r and 6r.
AHCTUNGTRENNUNG
result. However, a new species (7r) is formed in high yield
(Scheme 6). The nature of 7r was confirmed unambiguously
by X-ray crystallography to be the product of a 1,1-carbobo-
the weakening of the dative N!B bond in the oxazole
product. Disubstitution adjacent to the nitrogen atom of the
propargyl amide prompts 1,1-carboboration as a result of
1,3-allylic strain in the cyclised product. The isolation of the
vinyl boron derivatives in high yields suggests the possibility
of further application in organic synthesis. It is this aspect
that is the subject of on-going efforts.
ꢀ
ration reaction (Figure 6), in which one of the B C bonds of
B
N
with concurrent migration of the terminal H to the b-carbon
atom. Interestingly, this formation of 7r is selective for the
Z-product in which the amide-oxygen atom coordinates in-
tramolecularly to the boron atom to give a seven-membered
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Reactions of BACHTUNGTRENNUNG(C6F5)3 with Propargyl Amides
FULL PAPER
EtOAc, 1:1); 1H NMR (400 MHz, CDCl3, 298 K): d=7.53–7.38 (m, 5H,
Ph), 4.38 (s, br., 1H, CH2 rotamer), 4.01 (s, br., 1H, CH2 rotamer), 3.15
(s, br., 3H, CH3 rotamer), 3.07 (s, br., 3H, CH3 rotamer), 2.32 ppm (s,
Experimental Section
General considerations: With the exception of the synthesis of starting
materials, all reactions and manipulations were carried out under an at-
mosphere of dry, O2-free nitrogen using standard double-manifold techni-
ques with a rotary oil pump. A nitrogen-filled glove box (MBRAUN)
was used to manipulate solids including the storage starting materials,
room temperature reactions, product recovery and sample preparation
for analysis. Molecular sieves (4 ꢂ) were dried at 1208C for 24 h prior to
use. All solvents (toluene, CH2Cl2, THF, pentane, hexane) were dried by
employing a Grubbs-type column system (Innovative Technology), de-
gassed and stored over molecular sieves under a nitrogen atmosphere.
Deuterated solvents were dried over molecular sieves before use. Chemi-
cals were purchased from commercial suppliers and used as received.
N-Methyl-N-(prop-2-yn-1-yl)benzamide (1a),[7g] N-benzyl-N-(prop-2-yn-
1-yl)benzamide (1b),[7g] 4-methoxy-N-methyl-N-(prop-2-yn-1-yl)benz-
ꢁ
br., 1H, -C CH).
Synthesis of N-benzyl-N-(prop-2-yn-1-yl)benzamide, 1b: According to
general procedure B, N-benzylbenzamide (1.0 g, 4.73 mmol), NaH
(227 mg, 1.2 equiv, 60% in mineral oil), propargyl bromide (632 mL,
5.7 mmol, 1.2 equiv, 80% in toluene) were allowed to react in THF
(30 mL). Column chromatography on SiO2 (hexane/EtOAc, 9:1) afforded
1
the product as a colourless oil (781 mg, 3.13 mmol, 66%) whose H NMR
spectra were comparable with those previously reported.[7g] Rf =0.49
(hexane/EtOAc, 1:1); 1H NMR (400 MHz, CDCl3, 298 K): d=7.64–7.16
(m, 10H, Ar-H), 4.96 ꢀ4.60 (m, br., 2H CH2 rotamer), 4.29 (s, br., 1H,
CH2 rotamer), 3.88 (s, br., 1H, CH2 rotamer), 2.32 ppm (s, br., 1H,
ꢁ
-C CH).
Synthesis of N-4-dimethyl-N-(prop-2-yn-1-yl)benzamide, 1c: According
to general procedure A, N-methylpropargyl amine (420 mL, 5.0 mmol),
DMAP (12.2 mg), NEt3 (690 mL, 5.0 mmol) and p-toluoyl chloride
(661 mL, 5.0 mmol) were allowed to reacted in CH2Cl2 (15 mL). Column
chromatography on SiO2 (hexane/EtOAc, 8:1 to 3:2) afforded the prod-
uct as an off-white solid (798 mg, 4.26 mmol, 85%). Rf =0.37 (hexane/
EtOAc, 1:1); 1H NMR (400 MHz, CDCl3, 298 K): d=7.39 (m, br., 2H,
Ar-H), 7.21 (d, 3JHH =7.8 Hz, Ar-H), 4.41–3.94 (m, br., 2H, CH2 rotam-
er), 3.10 (s, br., 3H, CH3), 2.38 (s, 3H, CH3), 2.30 ppm (s, br., 1H,
ACHTUNGTRENNUNG
amide (1 f),[16] N-methyl-N-(prop-2-yn-1-yl)furan-2-carboxamide (1h),[7f]
N-phenyl-N-(prop-2-yn-1-yl)formamide (1i)[17] and 4-methyl-N-(prop-2-
yn-1-yl)benzamide (1l)[7a] were prepared according to literature methods.
N-(Prop-2-yn-1-yl)formamide
(1j),[18]
N-(prop-2-yn-1-yl)benzamide
(1k),[7a] N-(prop-2-yn-1-yl)adamantane-1-carboxamide (1o)[7a] N-(2-meth-
ylbut-3-yn-2-yl)benzamide (1r),[5b, 19] 5-methyl-2-(p-tolyl)oxazole (5l)[20] 4-
bromo-N-(prop-2-yn-1-yl)benzamide (1m),[21] 2-phenyl-N-(prop-2-yn-1-
yl)acetamide (1p),[7f] N-(prop-2-yn-1-yl)pentanamide (1r)[22] and 4-nitro-
-C CH); 13C NMR (500 MHz [D8]toluene, 298 K): d=170.8 (s), 140.0 (s),
N-(prop-2-yn-1-yl)benzamide (3n),[5d,
were synthesised previously. 1H,
20]
ꢁ
13C 11B and 19F NMR spectra were recorded on a Bruker Avance III, a
Bruker Avance 500 or a Varian Mercury 400 spectrometer. Chemical
shifts are expressed as parts per million (ppm, d) downfield of tetrame-
thylsilane (TMS) and are referenced to [D8]toluene, [D6]benzene,
[D8]THF, CDCl3 and CD2Cl2 as internal standards. NMR spectra were
referenced to CFCl3 (19F) and BF3·Et2O/CDCl3 (11B). All coupling con-
stants are absolute values and J values are expressed in Hertz (Hz). A
Perkin–Elmer Analyser was used for carbon, hydrogen and nitrogen ele-
mental analyses. High resolution mass spectrometry was performed in
house employing DART or electrospray ionisation techniques in positive-
ion mode. Mass spectral data were recorded on an AB/Sciex QStarXL
mass spectrometer (ESI) or a JEOL AccuTOF model JMS-T1000 LC
mass spectrometer (DART).
137.9 (s), 134.0 (s), 100.7 (s), 79.8 (s), 72.6 (s), 68.1 (s), 26.2 ppm (s); ele-
mental analysis calcd (%) for C12H13NO: C 76.98, H 7.00, N 7.48; found:
C 76.71, H 7.49, N 7.43; DART MS, m/z: 188.1 (calcd for [M+H]+:
188.1).
Synthesis of 4-bromo-N-methyl-N-(prop-2-yn-1-yl)benzamide, 1d: Ac-
cording to general procedure A, N-methylpropargyl amine (420 mL,
5.0 mmol), DMAP (12.2 mg), NEt3 (690 mL, 5.0 mmol) and p-bromoben-
zoyl chloride (1.10 g, 5.0 mmol) were allowed to react in CH2Cl2 (15 mL).
Column chromatography on SiO2 (hexane/EtOAc, 8:1 to 3:2) afforded
the product as
a white solid (840 mg, 3.33 mmol, 67%). Rf =0.26
(hexane/EtOAc, 1:1); 1H NMR (400 MHz, CDCl3, 298 K): d=7.56 (m,
2H, Ar-H), 7.37 (s, br., Ar-H), 4.36 (s, br., 1H, CH2 rotamer), 3.98 (s,
ꢁ
br., 1H, CH2 rotamer), 3.09 (s, br., CH3), 2.32 ppm (s, br., 1H, -C CH);
13C NMR (500 MHz, [D6]benzene, 298 K): d=169.4 (s), 135.1 (s), 131.7
(s), 129.3 (s), 124.2 (s), 78.9 (s), 72.6 ppm (s), the peaks due to the CH2
and CH3 groups could not be assigned presumably due to broadening of
peaks due to rotation about the amide bond; elemental analysis calcd
(%) for C11H10NOBr: C 52.41, H 4.00, N 5.57; found: C 52.29, H 3.84, N
5.50; DART MS, m/z: 252.0 (calcd for [M+H]+: 252.0).
Synthesis of N-propargylcarboxamides: General procedure A: N-Propar-
gylcarboxamides were prepared by a method similar to that previously
reported for N-benzyl-N-(prop-2-yn-1-yl)benzamide. TriethylACTHNUTRGNEaNUG mine
(1 equiv) and 4-dimethylaminopyridine (DMAP; 0.02 equiv) were added
to a solution of propargyl amine (1.0 equiv) in CH2Cl2 (ca. 20 mL) and
was stirred for 15 min. The solution was then cooled to 08C and the cor-
responding acyl chloride (1.0 equiv) was added dropwise. The resulting
mixture was stirred at this temperature for 30 min and was allowed to
warm to room temperature and was stirred for a further 3 h. After
quenching the reaction with water, the aqueous layer was extracted with
CH2Cl2 (2ꢃ). The combined organic phases were washed with brine,
dried with MgSO4, filtered, and the solvent was removed under vacuum
and the product purified by column chromatography or recrystallisation.
Synthesis of 2-bromo-N-methyl-N-(prop-2-yn-1-yl)benzamide, 1e: Ac-
cording to general procedure A, N-methylpropargyl amine (420 mL,
5.0 mmol), DMAP (12.2 mg), NEt3 (690 mL, 5.0 mmol) and 2-bromoben-
zoyl chloride (653 mL, 5.0 mmol) were allowed to react in CH2Cl2
(15 mL). Column chromatography on SiO2 (hexane/EtOAc, 8:1 to 3:2)
afforded the product as an off-white solid (855 mg, 3.4 mmol, 68%). Rf =
0.39 (hexane/EtOAc, 1:1); 1H NMR (400 MHz, [D8]toluene, 298 K): d=
7.59–7.23 (m, 4H, Ar H), 4.42 and 3.89 (m, 2H, CH2 rotamers), 3.20 and
General procedure B: To a solution of amide (1.0 equiv) in THF was
added NaH (1.2 equiv, 60% in mineral oil) at 08C. The solution was
warmed up to room temperature, stirred for 1 h, cooled to 08C and prop-
argyl bromide (1.2 equiv, 80% in toluene) added. The resulting mixture
was stirred at this temperature for 30 min and was allowed to warm to
room temperature and was stirred for a further 3 h. After quenching the
reaction with brine, the aqueous layer was extracted with CH2Cl2 (2ꢃ).
The combined organic phases were washed with brine, dried with
MgSO4, filtered, and the solvent was removed under vacuum and the
product purified by column chromatography or recrystallisation.
2.92 (s, 3H, CH3 rotamers), 2.28 ppm (m, 1H, -C CH); 13C NMR
ꢁ
(500 MHz [D8]toluene, 298 K): d=167.8 (s), 167.7 (s), 138.9 (s), 138.6 (s),
137.5 (s), 132.8 (s), 132.7 (s), 130.6 (s), 129.9 (s), 127.5 (s), 127.4 (s), 119.6
(s), 119.5 (s), 78.7 (s), 78.3 (s), 73.0 (s), 72.2 (s), 39.9 (s), 35.4(s), 34.4 (s),
31.5 ppm (s), two different rotamers; elemental analysis calcd (%) for
C11H10NOBr: C 52.41, H 4.00, N 5.56; found: C 52.25, H 4.00, N 5.56;
DART MS, m/z: 252.0 (calcd for [M+H]+: 252.0).
Synthesis of 4-methoxy-N-methyl-N-(prop-2-yn-1-yl)benzamide, 1 f: Ac-
cording to general procedure A, N-methylpropargyl amine (420 mL,
5.0 mmol), DMAP (12.2 mg), NEt3 (690 mL, 5.0 mmol) and p-methoxy-
benzoyl chloride (677 mL, 5.0 mmol) were allowed to react in CH2Cl2
(15 mL). Column chromatography on SiO2 (hexane/EtOAc, 8:1 to 3:2)
afforded the product as a colourless oil (724 mg, 3.56 mmol, 71%) whose
1H NMR spectra were comparable with those previously reported.[16] Rf =
0.30 (hexane/EtOAc, 1:1); 1H NMR (400 MHz, CDCl3, 298 K): d=7.47
(d, 3JHH =8.4 Hz, 2H, Ar-H), 6.91 (d, 3JHH =8.4 Hz, 2H, Ar-H), 4.20 (s,
Synthesis of N-methyl-N-(prop-2-yn-1-yl)benzamide, 1a: According to
general procedure A, N-methylpropargyl amine (420 mL, 5.0 mmol),
DMAP (12.2 mg), NEt3 (690 mL, 5.0 mmol) and benzoyl chloride
(690 mL, 5.0 mmol) were allowed to react in CH2Cl2 (15 mL). Column
chromatography on SiO2 (hexane/EtOAc, 8:1 to 3:2) afforded the prod-
uct as a colourless oil (662 mg, 3.82 mmol, 76%) whose 1H NMR spectra
were comparable with those previously reported.[7g] Rf =0.43 (hexane/
Chem. Eur. J. 2013, 19, 11928 – 11938
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11933

D. W. Stephan et al.
br., 2H, CH2), 3.83 (s, 3H, -OCH3), 3.11 (s, 3H, CH3), 2.31 ppm (s, 1H,
8.3 Hz, o-F), ꢀ157.4 (t, 1F, JFF =20.4 Hz, p-F), ꢀ164.3 ppm (m, 2F, m-F);
13C{1H} NMR (100 MHz, CD2Cl2, 298 K): d=166.0 (s), 148.7 (m), 140.9
(m), 137.9 (m), 137.9 (s), 131.4 (s), 131.1 (s), 125.6 (s), 76.0 (s), 74.5 (s),
40.1 ppm (s); elemental analysis calcd (%) for C28H9NOBF10: C 50.12; H
1.35; N 2.09; found: C 50.12, H 1.32; N 2.13; DART MS, m/z: 160.1
(calcd for [MꢀB
ion was observed.
Synthesis of 3a: BACTHNUGTRENUN(G C6F5)3 (205 mg, 0.4 mmol) was dissolved in toluene
ꢁ
-C CH).
Synthesis of N-methyl-4-nitro-N-(prop-2-yn-1-yl)benzamide, 1g: Accord-
ing to general procedure A, N-methylpropargyl amine (420 mL,
5.0 mmol), DMAP (12.2 mg), NEt3 (690 mL, 5.0 mmol) and p-nitrobenzo-
yl chloride (928 mg, 5.0 mmol) were allowed to react in CH2Cl2 (15 mL).
Column chromatography on SiO2 (hexane/EtOAc, 8:1 to 3:2) afforded
the product as a slightly yellow solid (753 mg, 3.45 mmol, 69%). Rf =0.42
(hexane/EtOAc, 1:1); 1H NMR (400 MHz, CDCl3, 298 K): d=8.29 (d,
3JHH =8.6 Hz, 2H, Ar-H), 7.67 (m, br., 2H, Ar-H), 4.40 (s, br., 1H, CH2
rotamer), 3.94 (s, br., 1H, CH2 rotamer), 3.19 and 3.13 (s, 3H, CH3 ro-
(C6F5)3]+: 160.1), no peak assignable to the molecular
ACHTUNGTRENNUNG
(ca. 2 mL) and was added to N-methyl-N-(prop-2-yn-1-yl)benzamide
(69 mg, 0.4 mmol). The reaction mixture was heated to 458C for four
days without stirring giving a brown/blue solution and a large crop of
small colourless crystals. The remaining solvent was decanted off to
afford colourless crystals of the product which were washed with pentane
(3ꢃ3 mL) and dried in vacuo to give pure 3a (251 mg, 0.37 mmol, 92%).
1H NMR (400 MHz, [D8]THF, 298 K): d=7.89 (m, 2H, o-H), 7.83 (tt,
3JHH =7.6 Hz, 4JHH =1.2 Hz, 1H, p-H), 7.69 (t, br., 3JHH =7.8 Hz, 2H, m-
H), 6.64 (s, br., 1H, C=CH), 4.36 (d, 4JHH =2.6 Hz, 2H, CH2), 3.52 ppm
(s, 3H, CH3); 11B NMR (128 MHz, [D8]THF, 298 K): d=ꢀ16.8 ppm (s);
19F NMR (377 MHz, [D8]THF, 298 K): d=ꢀ132.9 (d, 2F, 3JFF =22.1 Hz,
tamers), 2.40 and 2.31 ppm (s, 1H, -C CH rotamers); 13C NMR
ꢁ
(500 MHz, CDCl3, 298 K): d=169.0 (s), 148.6 (s), 141.7 (s), 128.3 (s),
128.1 (s), 77.9 (s, br.), 77.8 (s, br.), 73.9 (s), 72.9 (s), 41.5 (s), 36.6 (s),
33.1 ppm (s), extra peaks observed dure to different rotamers. Elemental
analysis calcd (%) for C11H10N2O3: C 60.55, H 4.62, N 12.84; found: C
60.23, H 4.92, N 12.73; DART MS, m/z: 219.1 (calcd for [M+H]+: 219.1).
Synthesis of N-methyl-N-(prop-2-yn-1-yl)furan-2-carboxamide, 1h: Ac-
cording to general procedure A, N-methylpropargyl amine (420 mL,
5.0 mmol), DMAP (12.2 mg), NEt3 (690 mL, 5.0 mmol) and 2-furoyl chlor-
ide (493 mL, 5.0 mmol) were allowed to react in CH2Cl2 (15 mL). Column
chromatography on SiO2 (hexane/EtOAc, 8:1 to 3:2) afforded the prod-
uct as a colourless liquid (575 mg, 3.5 mmol, 70%) whose 1H NMR spec-
tra were comparable with those previously reported.[7f] Rf =0.35 (hexane/
EtOAc, 1:1); 1H NMR (400 MHz, CDCl3, 298 K): d=7.51 (m, 1H, furan
H), 7.08 (d,1H, 3JHH =3.5 Hz, furan H), 6.48 (dd, 1H, 3JHH =3.5, 1.8 Hz,
furan H), 4.36 (s, br., 2H, CH2), 3.27 (s, br., 3H, CH3), 2.28 ppm (s, 1H,
o-F), ꢀ163.7 (t, 1F, JFF =20.2 Hz, p-F), ꢀ167.3 ppm (m, br., 2F, m-F);
3
13C{1H} NMR (100 MHz, [D8]THF, 298 K): d=170.5 (s), 149.4 (m, JCF
=
=
3
243.9 Hz), 143.5 (m, br.), 139.5 (m, 3JCF =248.0 Hz), 137.7 (m, JCF
248.5 Hz), 136.6 (s), 131.3 (s), 130.4 (s), 121.5 (s), 55.1 (s), 36.5 ppm (s),
the carbon atoms bonded to boron could not be observed above the
baseline; DART MS, m/z: 786.1 (calcd for [M+H]+: 786.1), 174.1 (calcd
for [(MꢀB
C29H11NOBF15: C 50.83, H 1.62, 2.04; found: C 50.86, H 1.67, N 2.25.
Synthesis of 3b: B(C6F5)3 (205 mg, 0.4 mmol) was dissolved in toluene
(C6F5)3)+H]+: 174.1); elemental analysis calcd (%) for
ACHTUNGTRENNUNG
ꢁ
-C CH).
AHCTUNGTRENNUNG
Synthesis of N-phenyl-N-(prop-2-yn-1-yl)formamide, 1i: According to
general procedure B, formanilide (969 mg, 8.0 mmol), NaH (640 mg,
2.0 equiv, 60% in mineral oil), propargyl bromide (980 mL, 8.8 mmol,
1.1 equiv, 80% in toluene) were allowed to react in THF (40 mL).
Column chromatography on SiO2 (hexane/EtOAc, 4:1) afforded the
(3 mL) and was added to N-benzyl-N-(prop-2-yn-1-yl)benzamide
(100 mg, 0.4 mmol). The reaction mixture was heated to 458C for four
days without stirring. The solution was allowed to cool to 258C and the
solvent removed in vacuo to give an orange oil. The oil was recrystallised
from the cooling of a hot hexane/CH2Cl2 solution (CH2Cl2 was added
dropwise to a mixture of the crude product in hexane (ca. 1 mL) until all
precipitates were dissolved) to afford colourless crystals of the product
(257 mg, 84%, 0.34 mmol). 1H NMR (400 MHz, CD2Cl2, 298 K): d=
7.82–7.78 (m, 3H, Ar-H), 7.63 (m, 2H, Ar-H), 4.45–7.37 (m, 3H, Ar-H),
1
product as an orange oil (450 mg, 2.83 mmol, 35%) whose H NMR spec-
tra were comparable with those previously reported.[17] Rf =0.26 (hexane/
EtOAc, 4:1); 1H NMR (400 MHz, CDCl3, 298 K): d=8.42 (s, 1H, alde-
hyde H), 7.44 (m, 2H, Ph-H), 7.35–7.29 (M, 3 h, Ph-H), 4.55 (d, 1H,
4
4JHH =2.5 Hz, CH2), 2.22 ppm (t, JHH =2.5 Hz, -C CH).
3
ꢁ
7.05 (d, 2H, JHH =7.8 Hz, Ar-H), 6.49 (s, br., C=C-H), 4.87 (s, 2H, CH2),
3.93 ppm (d, 2H, 4JHH =2.7 Hz); 11B NMR (128 MHz, [D8]toluene,
298 K): d=ꢀ16.4 ppm (s); 11B NMR (128 MHz, CD2Cl2, 298 K): d=
ꢀ17.0 ppm (s); 19F NMR (377 MHz, [D8]toluene, 298 K): d=132.2 (d, 2F,
Synthesis of 4-methyl-N-(prop-2-yn-1-yl)benzamide, 1l: According to
general procedure A, propargyl amine (512 mL, 8.0 mmol), DMAP
(12.2 mg), NEt3 (1.10 mL, 8.0 mmol) and p-toluoyl chloride (1.06 mL,
8.0 mmol) were allowed to react in CH2Cl2 (25 mL). Recrystallisation
from pentane/CH2Cl2 afforded the product as an off-white solid (980 mg,
5.66 mmol, 71%) whose 1H NMR spectra were comparable with those
previously reported.[7a] Rf =0.42 (hexane/EtOAc, 1:1); 1H NMR
(400 MHz, CDCl3, 298 K): d=7.68 (d, 3JHH =8.11 Hz, 2H, Ar-H), 7.24
J
FF =20.5 Hz, o-F), 160.7 (t, 1F, JFF =20.6 Hz, p-F), 165.1 ppm (m, 2F, m-
F); 19F NMR (377 MHz, CD2Cl2, 298 K): d=133.2 (d, 2F, JFF =22.7 Hz, o-
F), 161.9 (t, 1F, JFF =20.4 Hz, p-F), 166.1 ppm (m, 2F, m-F); 13C{1H}
NMR (100 MHz, CD2Cl2, 298 K): d=170.9 (s), 148.7 (m, 1JCF =243 Hz),
142.1 (m), 139.0 (m, 1JCF =246 Hz), 137.2 (m, 1JCF =250 Hz), 137.1 (s),
130.8 (s), 130.7 (s), 130.4 (s), 130.4 (s), 130.2 (s), 128.4 (s), 119.8 (s), 51.3
(s), 53.6 ppm (s), the carbon atoms bonded to boron could not be ob-
served above the baseline; DART MS, m/z: 762.1 (calcd for [M+H]+:
(3JHH =8.1 Hz, 2H, Ar-H), 6.22 (m, br., 1H, NH), 4.25 (m, 2H, CH2),
4
ꢁ
2.24 (s, 3H, CH3), 2.28 ppm (t, JHH =2.4 Hz, 1H, -C CH).
Synthesis of 2c: B
(0.7 mL) and was added to the N,4-dimethyl-N-(prop-2-yn-1-yl)benz-
ACHTUNGTRENNUNGamide (19 mg, 0.1 mmol). The reaction mixture was left for 4 h at 458C
ACHTUNGTRENNUNG(C6F5)3 (51 mg, 0.1 mmol) was dissolved in [D8]toluene
762.1), 250.1 (calcd for [(MꢀB
(C6F5)3)+H]+: 250.1); elemental analysis
ACHTUNGTRENNUNG
calcd (%) for C35H15NOBF15: C 55.22, H 1.99, 1.84; found: C 55.94, H
2.36, N 2.03.
resulting in a blue solution and colourless crystals of the product (58 mg,
83%, 0.08 mmol). 11B NMR (128 MHz, [D8]toluene, 298 K): d=0.7 ppm
(s, br.); 19F NMR (377 MHz, [D8]toluene, 298 K): d=132.2 (s, br., 2F, o-
F), 157.6 (m, 1F, p-F), 163.9 ppm (m, 2F, m-F).
Synthesis of 3c: BACHTNUTRGNEG(UN C6F5)3 (205 mg, 0.4 mmol) was dissolved in toluene
(3 mL) and was added to N-4-dimethyl-N-(prop-2-yn-1-yl)benzamide
(75 mg, 0.4 mmol). The reaction mixture was heated to 458C for four
days without stirring to give a deep blue solution. Cooling of the solution
resulted in precipitation of the product as colourless needles. Addition of
pentane (5 mL) to the suspension followed by removal of the liquid
phase by pipette and subsequent drying in vacuo afforded the crude
product, which was washed with pentane (2ꢃ3 mL) and dried under
Synthesis of 2i: BACHTUNGTRENNUNG(C6F5)3 (204 mg, 0.4 mmol) was dissolved in toluene
(4 mL) and was added to N-phenyl-N-(prop-2-yn-1-yl)formamide (64 mg,
0.4 mmol). The reaction mixture was heated to 458C for four days result-
ing in a red solution. Removal of the solvent in vacuo afforded an oil
which was recrystallised from a hexane/THF solution to give the pure
product as colourless crystals (131 mg, 0.20 mmol, 49%). 1H NMR
(400 MHz, CD2Cl2, 298 K): d=8.03 (s, 1H, aldehyde H), 7.58–7.53 (m,
3H, Ph-H), 7.39–7.34 (m, 2H, Ph-H), 4.81 (d, 4JHH =2.5 Hz, CH2),
vacuum to give the pure product as a light grey solid (150 mg, 53%,
3
0.21 mmol). 1H NMR (400 MHz, CD2Cl2, 298 K): d=7.73 (d, JHH
=
3
8.1 Hz, 2H, Ar-H), 7.49 (d, JHH =8.1 Hz, 2H, Ar-H), 6.53 (s, br., 1H, C=
CH), 4.34 (s, br., 2H, CH2), 3.48 (s, 3H, CH3), 2.51 ppm (s, 3H, CH3); in
situ 11B NMR (128 MHz, [D8]toluene, 298 K):d= ꢀ16.4 ppm (s);
11B NMR (128 MHz, CD2Cl2, 298 K): d=ꢀ16.8 ppm (s); in situ 19F NMR
(377 MHz, [D8]toluene, 298 K): d=ꢀ132.1 (d, 2F, JFF =21.4 Hz, o-F),
ꢀ161.1 (t, 1F, JFF =20.5 Hz, p-F), ꢀ165.3 ppm (m, 2F, m-F); 19F NMR
0.86 ppm (s, br., 1H, -C CH); 11B NMR (128 MHz, [D8]toluene, 298 K):
ꢁ
d=1.5 ppm (s); 11B NMR (128 MHz, CD2Cl2, 298 K): d=1.4 ppm (s);
19F NMR (377 MHz, [D8]toluene, 298 K): d=ꢀ134.6 (dd, 2F, JFF =23.7,
8.7 Hz, o-F), ꢀ156.0 (t, 1F, JFF =20.6 Hz, p-F), ꢀ163.5 ppm (m, 2F, m-F);
19F NMR (377 MHz, CD2Cl2, 298 K): d=ꢀ134.7 (dd, 2F,
JFF =23.5,
11934
www.chemeurj.org
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 11928 – 11938

Reactions of BACHTUNGTRENNUNG(C6F5)3 with Propargyl Amides
FULL PAPER
(377 MHz, CD2Cl2, 298 K): d=ꢀ133.1 (d, 2F, JFF =22.1 Hz, o-F), ꢀ162.1
(m, 1F, p-F), ꢀ166.2 ppm (m, 2F, m-F); 13C{1H} NMR (100 MHz, CD2Cl2,
298 K): d=170.5 (s), 149.4 (s), 148.8 (m, 1JCF =240.1 Hz), 141.7 (s, br.),
139.1 (m, 1JCF =246.4 Hz), 137.0 (m, 1JCF =247.1 Hz), 131.2 (s), 130.6 (s),
121.6 (q, br., JCB =52.9 Hz), 116.7 (s), 54.7 (s), 37.0 (s), 22.3 ppm (s), the
carbon atoms bonded to boron in BACTHNUTGRNE(UNG C6F5) could not be observed above
298 K): d=ꢀ132.1 (d, 2F, JFF =21.5 Hz, o-F), ꢀ161.1 (t, 1F, JFF =20.6 Hz,
p-F), ꢀ165.3 (m, 2F, m-F); 19F NMR (377 MHz, CD2Cl2, 298 K): d=
ꢀ133.2 (d, 2F, JFF =22.2 Hz, o-F), ꢀ162.1 (t, 1F, JFF =20.3 Hz, p-F),
ꢀ166.2 ppm (m, 2F, m-F); 13C{1H} NMR (100 MHz, CD2Cl2, 298 K): d=
169.5 (s), 166.9 (s), 148.9 (m, 1JCF =242 Hz), 139.1 (m, 1JCF =248 Hz),
138.6 (s, toluene), 137.3 (m, 1JCF =248 Hz), 133.4 (s), 129.5 (s, toluene),
128.7 (s, toluene), 125.8 (s, toluene), 116.1 (s), 111.1 (s), 56.7 (s), 54.8 (s),
21.5 ppm (s, toluene), the signals due to the carbon atoms bonded to
boron could not be observed; elemental analysis calcd (%) for
C30H13NO2BF15·0.33 toluene: C 52.06, H 2.12, N 1.88; found: C 52.56, H
2.38, N 2.71; DART MS, m/z: 716.1 (calcd for [M+H]+: 716.1), 204.1
1
the baseline; elemental analysis calcd (%) for C30H13NOBF15: C 51.53, H
1.87, N 2.00; found: C 52.59, H 2.96, N 2.25; DART MS, m/z: 700.1
(calcd for [M+H]+: 700.1), 188.1 (calcd for [(MꢀB
(C6F5)3)+H]+: 188.1).
ACHTUNGTRENNUNG
Synthesis of 3d: BACHTUNGTRENNUNG(C6F5)3 (205 mg, 0.4 mmol) was dissolved in toluene
(3 mL) and was added to N-benzyl-N-(prop-2-yn-1-yl)benzamide (69 mg,
0.4 mmol). The reaction mixture was heated to 458C for four days with-
out stirring giving a pale orange solution and a small amount of crystals.
Cooling the solution to ꢀ358C afforded a large quantity of crystals. The
solution was decanted off and the crystals washed with pentane (3ꢃ
2 mL) and the resulting colourless crystals were dried in vacuo to yield
the pure product (227 mg, 74%, 0.30 mmol). 1H NMR (400 MHz,
[D8]THF, 298 K): d=7.90 (s, 4H, Ar-H), 6.44 (s, br., 1H, C=CH), 4.36 (d,
4JHH =2.5 Hz, CH2), 3.51 ppm (s, 3H, CH3); 11B NMR (128 MHz,
[D8]toluene, 298 K): d=ꢀ16.4 ppm (s); 11B NMR (128 MHz, [D8]THF,
298 K): d=ꢀ16.7 ppm (s); 19F NMR (377 MHz, [D8]THF, 298 K): d=
ꢀ132.8 (d, 2F, JFF =22.1 Hz, o-F), ꢀ163.6 (t, 1F, JFF =20.1 Hz, p-F),
ꢀ167.2 ppm (m, 2F, m-F); 13C{1H} NMR (100 MHz, [D8]THF, 298 K): d=
170.0 (s), 149.4 (m, 1JCF =238 Hz), 143.4 (s), 149.4 (m, 1JCF =246 Hz),
137.5 (m, 1JCF =252 Hz), 133.9 (s), 132.9 (s), 131.8 (s), 120.5 (s), 55.5 (s),
36.5 ppm (s), the carbon atoms bonded to boron could not be observed
above the baseline; elemental analysis calcd (%) for C29H10NOBF15Br: C
45.59, H 1.32, N 1.83; found: C 45.53, H 1.46, N 1.80; DART MS, m/z:
(calcd for [(MꢀB
Synthesis of 3g: B
(3 mL) and was added to the N-methyl-4-nitro-N-(prop-2-yn-1-yl)benz-
AHCTUNGERTGaNNUN mide (87 mg, 0.4 mmol). The reaction mixture was left for two days at
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
458C resulting in a yellow solution and colourless crystals of the product.
The solution was decanted off and the crystals washed with pentane (3ꢃ
2 mL) and the product dried in vacuo to afford the product as a pale
yellow crystalline solid (266 mg, 91%, 0.36 mmol). 1H NMR (400 MHz,
3
[D8]THF, 298 K): d=8.51 (d, 3JHH =9.0 Hz, 2H, Ar-H), 8.22 (d, JHH
=
9.0 Hz, 2H, Ar-H), 6.48 (s, br., 1H, -C=CH), 4.43 (s, br., 2H, CH2),
3.54 ppm (s, 3H, CH3); 11B NMR (128 MHz, [D8]THF, 298 K): d=
ꢀ16.9 ppm (s); 19F NMR (377 MHz, [D8]THF, 298 K): d=ꢀ133.0 (t,
3JFF =21.6 Hz, 2F, o-F), ꢀ163.6 (t, 3JFF =20.2 Hz, 1F, p-F), ꢀ167.2 ppm
(m, 2F, m-F); 13C{1H} NMR (100 MHz, [D8]THF, 298 K): d=169.5 (s),
152.9 (s), 149.4 (m, 1JCF =241 Hz), 139.6 (m, 1JCF =245 Hz), 137.7 (m,
1JCF =250 Hz), 132.8 (s), 126.8 (s), 125.2 (s), 55.2 (s), 36.5 ppm (s), the
carbon atoms bonded to boron could not be observed; elemental analysis
calcd (%) for C29H10N2O3BF15: C 47.70, H 1.38, N 3.84; found: C 47.66,
H 1.51, N 3.83; DART MS, m/z: 731.1 (calcd for [M+H]+: 731.1), 219.1
764.0 (calcd for [M+H]+: 764.0), 252.0 (calcd for [(MꢀB
(C6F5)3)+H]+:
ACHTUNGTRENNUNG
252.0).
(calcd for [(MꢀB
ACHTUNGTRENNUNG
Synthesis of 3e: B
(3 mL) and was added to 2-bromo-N-methyl-N-(prop-2-yn-1-yl)benz-
amide (100 mg, 0.4 mmol). The reaction mixture was heated to 458C for
ACHTUNGTRENNUNG(C6F5)3 (205 mg, 0.4 mmol) was dissolved in toluene
Synthesis of 3h: B
AHCTUNGTRENNUNG
U
(3 mL) and was added to the N-methyl-N-(prop-2-yn-1-yl)furan-2-carbox-
amide (65 mg, 0.4 mmol). The reaction mixture was heated to 458C for
four days without stirring. The solution was allowed to cool to 258C caus-
ing the product to crash out of solution. The solid was redissolved by the
addition of THF (ca. 0.5 mL). Slow evaporation of the solvent afforded
colourless crystals of the product (184 mg, 68%, 0.27 mmol); 1H NMR
(400 MHz, [D8]THF, 298 K): d=8.22 (dd, J=1.7 Hz, 0.78 Hz, 1H, furan
H), 7.88 (dd, J=3.9 Hz, 0.78 Hz, 1H, furan H), 6.94 (dd, J=3.9 Hz,
1.71 Hz, 1H, furan H), 6.37 (s, br., alkene H), 4.26 (m, br., 2H, CH2),
3.62 ppm (s, 3H, CH3); 11B NMR (128 MHz, [D8]toluene, 298 K): d=
ꢀ16.4 ppm (s); 19F NMR (377 MHz, [D8]toluene, 298 K): d=ꢀ132.1 (d,
2F, JFF =21.6 Hz, o-F), ꢀ161.1 (t, 1F, JFF =20.8 Hz, p-F), ꢀ165.3 ppm (m,
2F, m-F); 13C{1H} NMR (100 MHz, [D8]THF, 298 K): d=159.1 (s), 153.2
four days without stirring to give a pale purple solution. Removal of the
solvent to generate a saturated solution followed by layering with hexane
afforded small colourless crystals of the product. The remaining solution
was decanted off and the resulting solid washed with hexane (3ꢃ3 mL)
and dried in vacuo to give the pure product (157 mg, 0.21 mmol, 51%).
1H NMR (400 MHz, CD2Cl2, 298 K): d=7.86–7.84 (m, 1H, Ar-H), 7.69–
4
7.57 (m, 3H, Ar-H), 6.60 (s, br., 1H, -C=CH), 4.37 (d, JHH =2.3 Hz, 2H,
CH2), 3.26 ppm (s, 3H, CH3); 11B NMR (128 MHz, [D8]toluene, 298 K):
d=ꢀ16.4 ppm (s); 11B NMR (128 MHz, CD2Cl2, 298 K): d=ꢀ16.9 (s);
19F NMR (377 MHz, [D8]toluene, 298 K): d=ꢀ132.3 (d, 2F, JFF =21.8 Hz,
o-F), ꢀ160.8 (t, 3JFF =20.9 Hz, 1F, p-F), ꢀ165.1 ppm (m, br., 2F, m-F);
19F NMR (377 MHz, [D8]toluene, 298 K): d=ꢀ133.1 (d, 2F, JFF =22.4 Hz,
o-F), ꢀ161.9 (t, 3JFF =20.6 Hz, 1F, p-F), ꢀ166.0 ppm (m, br., 2F, m-F);
(s), 149.4 (m, JCF =240 Hz), 143.7 (m), 139.7 (m, JCF =246 Hz), 138.4 (s),
137.7 (m, 1JCF =245 Hz), 127.2 (s), 115.0 (s), 54.4 (s), 35.2 ppm (s), the
carbon atoms bonded to boron could not be observed; elemental analysis
calcd (%) for C30H15NPBF10·C7H8: C 53.22, H 2.23, N 1.83; found: C
53.04, H 2.23, N 1.83; DART MS, m/z: 676.1 (calcd for [M+H]+: 676.1),
1
1
1
13C{1H} NMR (100 MHz, CD2Cl2, 298 K): d=171.4 (s), 148.8 (m, JCF
=
238 Hz), 142.4 (m), 139.2 (m, 1JCF =248 Hz), 137.3 (m, 1JCF =248 Hz),
1
136.6 (s), 135.0 (s), 131.1 (s), 129.2 (s), 123.3 (q, JBC ca. 51 Hz), 122.0 (s),
121.8 (s), 36.6 ppm (s), the carbon atom bonded to boron in the C6F5
groups could not be observed; elemental analysis calcd (%) for
C29H10NOBF15Br: C 45.59, H 1.32, N 1.83; found: C 45.52, H 1.49, N
1.89; DART MS, m/z: 764.0 (calcd for [M+H]+: 764.0), 252.0 (calcd for
164.1 (calcd for [MꢀB
Synthesis of 3k: B(C6F5)3 (205 mg, 0.4 mmol) was dissolved in toluene
(C6F5)3]+: 164.1).
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
(6 mL) and was added to N-(prop-2-yn-1-yl)benzamide 1k (64 mg,
0.4 mmol). The reaction mixture was heated to 458C for six days without
stirring giving a yellow solution. Slow evaporation of the solent afforded
small colourless crystals of 3k which were washed with pentane (3ꢃ
3 mL) and dried in vacuo to afford the pure product (202 mg, 75%,
0.30 mmol). 1H NMR (400 MHz, [D8]THF, 298 K): d=11.72 (s, br., 1H,
NH), 8.04 (d, 3JHH =7.5 Hz, 2H, o-H), 7.87 (t, 3JHH =7.5 Hz, 1H, p-H),
7.68 (t, 3JHH =7.5 Hz, 2H, m-H), 7.20–7.06 (m, toluene), 6.51 (s, 1H, -C=
CH), 4.24 (s, 2H, CH2), 2.30 ppm (s, toluene); 11B NMR (128 MHz,
[D8]THF, 298 K): d=ꢀ16.7 ppm (s); 19F NMR (377 MHz, [D8]THF,
298 K): d=ꢀ132.8 (d, 2F, JFF =21.5 Hz, o-F), ꢀ163.7 (t, 1F, JFF =20.1 Hz,
[(MꢀB
Synthesis of 3 f: B
(2 mL) and was added to 4-methoxy-N-methyl-N-(prop-2-yn-1-yl)benz-
amide (81 mg, 0.4 mmol). The reaction mixture was heated to 458C for
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
four days without stirring giving a blue/purple solution. Layering of pen-
tane (5 mL) on top of the solution afforded very small colourless crystals
of the product. The remaining solution was decanted off and the solid
washed with pentane (3ꢃ3 mL) and dried in vacuo to give the pure prod-
uct (241 mg, 79%, 0.32 mmol).1H NMR (400 MHz, CD2Cl2, 298 K): d=
7.84 (d, 3JHH =9.0 Hz, 2H, Ar-H), 7.14 (d, 3JHH =9.0 Hz, 2H, Ar-H), 6.50
(s, br., 1H, -C=CH), 4.29 (d, br., 4JHH =2.4 Hz, 2H, CH2), 3.94 (s, 3H,
CH3), 3.47 (s, 3H, CH3), 0.3 equivalents of residual toluene solvent was
also observed at 7.24 (m), 7.16 (m) and 2.34 ppm (s) ppm; 11B NMR
(128 MHz, CD2Cl2, 298 K): ꢀ16.9 ppm (s); 11B NMR (128 MHz,
[D8]toluene, 298 K): d=ꢀ16.3 ppm (s); 19F NMR (377 MHz, [D8]toluene,
p-F), ꢀ167.3 ppm (m, 2F, m-F); 13C{1H} NMR (100 MHz, [D8]THF,
1
298 K): d=172.1(s), 149.4 (m, 1JCF =241 Hz), 146.0 (m), 139.7 (m, JCF
=
241 Hz), 137.8 (s, toluene), 137.5 (m, 1JCF =245 Hz), 130.7 (s), 130.5 (s),
129.8 (s, toluene), 129.1 (s, toluene), 126.2 (s, toluene), 121.6 (s), 47.1 (s),
21.7 ppm (s, toluene), the signals due to the carbon atoms bonded to
Chem. Eur. J. 2013, 19, 11928 – 11938
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11935

D. W. Stephan et al.
boron could not be observed; elemental analysis calcd (%) for
C28H9NOBF15·0.5 toluene: C 52.75, H 1.83, N 1.95; found: C 53.14, H
2.00, N 1.95; ESI(+) MS, m/z: 671.1 (calcd for [M]+: 671.1).
br., 1F, o-F), ꢀ131.6 (s, br., 1F, o-F), ꢀ132.8 (s, br., 4F, o-F), ꢀ155.1 (t,
3JFF =19.5 Hz, 1F, p-F), ꢀ156.8 (t, 3JFF =20.9 Hz, 2F, p-F), ꢀ162.0 (t, br.,
3
3JFF =19.7 Hz, 1F, m-F),-163.2 (t, br., JFF =20.3 Hz, 1F, m-F), ꢀ164.4 ppm
(t, br., 3JFF =20.9 Hz, 4F, m-F) (the C6F5 groups are not equivalent);
11B NMR (128 MHz, [D8]toluene, 298 K): d=ꢀ6.8 ppm (s, br.).
Synthesis of 3l, (method a): B
[D8]toluene (0.7 mL) and was added to 4-methyl-N-(prop-2-yn-1-yl)benz-
amide (17 mg, 0.1 mmol). The reaction mixture was left at room tempera-
ACHTNUGTERN(NGNU C6F5)3 (51 mg, 0.1 mmol) was dissolved in
N
Synthesis of 3m: BACTHUNGTERNU(NG C6F5)3 (205 mg, 0.4 mmol) was dissolved in toluene
ture for seven days without stirring to give a pale yellow solution result-
ing in the cyclised product in 45% yield by NMR spectroscopy. 11B NMR
(128 MHz, [D8]toluene, 298 K): d=ꢀ16.4 ppm (s); 19F NMR (377 MHz,
[D8]toluene, 298 K): d=ꢀ131.2 (d, 2F, JFF =22.7 Hz, o-F), ꢀ161.3 (t,
3JFF =20.8 Hz, 1F, p-F), ꢀ165.3 ppm (m, br., 2F, m-F).
(8 mL) and was added to 4-bromo-N-(prop-2-yn-1-yl)benzamide (95 mg,
0.4 mmol). The reaction mixture was heated to 458C for six days without
stirring giving a pale yellow solution. Evaporation of the solvent afforded
small colourless needles of the product. Removal of the remaining sol-
vent by pipette followed by washing with pentane (3ꢃ3 mL) and drying
in vacuo afforded the pure product (154 mg, 51%, 0.21 mmol). 1H NMR
(400 MHz, [D8]THF, 298 K): d=11.76 (s, br., 1H, NH), 7.96–7.90 (m,
4H, Ar-H), 6.51 (s, 1H, -C=CH), 4.27 ppm (s, 2H, CH2), residual toluene
solvent was also observed; 11B NMR (128 MHz, [D8]THF, 298 K): d=
ꢀ16.7 ppm (s); 19F NMR (377 MHz, [D8]THF, 298 K): d=ꢀ132.8 (d, 2F,
Synthesis of 3l, (method b): B
in toluene (4 mL) and was added to 4-methyl-N-(prop-2-yn-1-yl)benz-
amide (68 mg, 0.4 mmol). The reaction mixture was left at room tempera-
ACHTNUGTERN(NGNU C6F5)3 (200 mg, 0.4 mmol) was dissolved
ACHTUNGTRENNUNG
ture for seven days without stirring to give a pale yellow solution. Evapo-
ration of the toluene solvent afforded small colourless crystals of the
product. The remaining solvent was removed and the product washed
with pentane (2ꢃ3 mL) and dried in vacuo to yield the pure product as a
white solid (117 mg, 43%, 0.17 mmol). 1H NMR (400 MHz, CD2Cl2,
298 K): d=8.09 (s, br.), 7.85 (d, 3JHH =8.3 Hz, 2H, Ar-H), 7.50 (d, J=
8.3 Hz, 2H, Ar-H), 6.65 (s, br., C=CH), 4.29 (s, br., 2H, CH2), 2.53 (s,
3H, CH3), ca. 0.5 equiv toluene was observed at 7.25 (m) and 7.16 ppm
(m); 11B NMR (128 MHz, CD2Cl2, 298 K): ꢀ16.9 ppm (s); 19F NMR
(377 MHz, CD2Cl2, 298 K): d=ꢀ133.1 (d, 2F, JFF =22.0 Hz, o-F), ꢀ162.0
J
FF =21.4 Hz, o-F), ꢀ163.6 (t, 1F, JFF =20.2 Hz, p-F), ꢀ167.2 ppm (m, 2F,
m-F); 13C{1H} NMR (100 MHz, [D8]THF, 298 K): d=171.6 (s), 149.3 (m,
1JCF =241 Hz), 146.0 (m), 139.5 (m, 1JCF =245 Hz), 138.6 (s, toluene),
137.8 (m, 1JCF =243 Hz), 134.2 (s), 133.1 (s), 131.9 (s), 129.8 (s, toluene),
129.1 (s, toluene), 126.2 (s, toluene), 120.7 (s), 47.3 (s), 21.6 ppm (s, tol-
uene), the signals due to the carbon atoms bonded to boron could not be
observed; Elemental analysis calcd (%) for C28H8NOBF15Br·toluene: C
49.91, H 1.91, N 1.66; found: C 49.36, H 2.20, N 1.66; ESI+ MS, m/z:
749.0, 751.0 (calcd for [M]+: 749.0, 751.0), 512.0 (calcd for [(B
ACHTUNGTRENNUNG(C6F5)3)+
(t, 1F,
J
FF =20.1 Hz, p-F), ꢀ166.1 ppm (m, 2F, m-F); 13C{1H} NMR
H]+: 512.0).
1
(100 MHz, CD2Cl2, 298 K): d=171.8 (s), 151.7 (s), 148.8 (m, JCF
=
235 Hz), 144.4 (m), 139.0 (m, 1JCF =246 Hz), 138.6 (s, tol), 137.3 (m,
1JCF =246 Hz), 131.7 (s), 130.1 (s), 129.5 (s, tol), 128.7 (s, tol), 125.8 (s,
tol), 116.0 (s), 46.3 (s, br.), 22.7 (s), 21.7 ppm (s, tol), B-bound carbon
atoms were not be observed; elemental analysis calcd (%) for
C29H11NOBF15·0.5 toluene: C 53.38, H 2.07, N 1.92; found: C 53.58, H
2.26, N 1.93; DART MS, m/z: 686.1 (calcd for [M+H]+: 686.1), 174.1
Synthesis of 3n: BACTHUNGTERNU(NG C6F5)3 (205 mg, 0.4 mmol) was dissolved in toluene
(8 mL) and was added to 4-nitro-N-(prop-2-yn-1-yl)benzamide (82 mg,
0.4 mmol) immediately giving a yellow solution and precipitate. The reac-
tion mixture was heated to 458C for one day without stirring. Removal
of the solvent by pipette followed by washing the remaining solid with
pentane (3ꢃ3 mL) and drying in vacuo afforded the pure product
(242 mg, 85%, 0.34 mmol). 1H NMR (400 MHz, [D8]THF, 298 K): d=
(calcd for [MꢀB
ACHTUNGTRENNUNG
3
3
8.52 (d, JHH =9.0 Hz, 2H, m-H), 8.28 (d, JHH =9.0 Hz, 2H, o-H), 6.56 (s,
1H, -C=CH), 4.34 (s, 2H, CH2), 2.31 ppm (s, 3H, CH3), residual toluene
solvent was also observed; 11B NMR (128 MHz, [D8]THF, 298 K): d=
ꢀ16.7 ppm (s); 19F NMR (377 MHz, [D8]THF, 298 K): d=ꢀ132.9 (d, 2F,
Synthesis of 4l, (method a): BAHCNUTGTRENNUNG
toluene (3 mL) and was added to 4-methyl-N-(prop-2-yn-1-yl)benzamide
(69 mg, 0.4 mmol). The reaction mixture was heated to 458C for four
days without stirring. Slow evaporation of the toluene solvent afforded
colourless crystals of the product (163 mg, 0.24 mmol, 60%). 1H NMR
(400 MHz, [D8]toluene, 298 K): d=7.08 (d, 3JHH =8.1 Hz, 2H, o-H), 6.83
(s, br., 1H, C-H oxazole), 6.56 (d, 3JHH =8.1 Hz, 2H, m-H), 1.86 (s, 3H,
CH3), 1.54 (s, 3H, CH3); 1H NMR (400 MHz, CD2Cl2, 298 K): 7.30 (d,
3JHH =8.3 Hz, 2H, o-H), 7.13 (d, 3JHH =8.1 Hz, 2H, m-H), 7.10 (s, br.,
1H, C-H oxazole), 2.48 (d, 4JHH =1.0 Hz, 3H, CH3), 2.35 ppm (s, 3H,
CH3); 11B NMR (128 MHz, [D8]toluene, 298 K): d=ꢀ6.7 ppm (s, br.);
11B NMR (128 MHz, CD2Cl2, 298 K): d=ꢀ7.1 ppm (s); 19F NMR
(377 MHz, [D8]toluene, 298 K): d=ꢀ129.5 (s, br., 1F, o-F), ꢀ131.6 (s, br.,
1F, o-F), ꢀ132.8 (s, br., 4F, o-F), ꢀ155.3 (t, 3JFF =19.5 Hz, 1F, p-F),
J
FF =21.5 Hz, o-F), ꢀ163.5 (t, 1F, JFF =20.2 Hz, p-F), ꢀ167.2 ppm (m, 2F,
m-F); 13C{1H} NMR (100 MHz, [D8]THF, 298 K): d=171.1 (s), 153.3 (s),
149.4 (m, 1JCF =237 Hz), 146.6 (m), 139.6 (m, 1JCF =246 Hz), 138.6 (s, tol-
uene), 137.6 (m, 1JCF =244 Hz), 129.8 (s, toluene), 129.1 (s, toluene),
126.9 (s), 126.2 (s, toluene), 125.5 (s), 47.6 (s), 21.6 ppm (s, toluene), the
signals due to the carbon atoms bonded to boron could not be observed;
elemental analysis calcd (%) for C28H8N2O3BF15·toluene: C 52.07, H 1.87,
N 3.47; found: C 51.90, H 2.13, N 3.50; DART MS, m/z: 757.0 (calcd for
[M+K]+: 757.0), 739.0 (calcd for [M+Na]+: 739.0), 734.1 (calcd for
[M+NH4]+: 734.1), 205.1 (calcd for [(MꢀB
Synthesis of 3o: BACTHUNGTERNU(NG C6F5)3 (255 mg, 0.5 mmol) was dissolved in toluene
(C6F5)3)+H]+: 205.2).
ACHTUNGTRENNUNG
3
3
ꢀ156.9 (t, JFF =20.9 Hz, 2F, p-F), ꢀ162.1 (t, br., JFF =19.7 Hz, 1F, m-F),-
163.3 (t, br., 3JFF =20.3 Hz, 1F, m-F), ꢀ164.4 ppm (t, br., 3JFF =20.9 Hz,
4F, m-F) (the C6F5 groups are not equivalent); 19F NMR (377 MHz,
CD2Cl2, 298 K): d=ꢀ129.2 (m, 1F, o-F), ꢀ132.7 (m, 1F, o-F), ꢀ133.2 (s,
br., 4F, o-F), ꢀ157.1 (t, 3JFF =19.3 Hz, 1F, p-F), ꢀ158.1 (t, 3JFF =20.3 Hz,
2F, p-F), ꢀ163.5 (m, br., 1F, m-F),-163.9 (m, br., 1F, m-F), ꢀ165.3 ppm
(m, 4F, m-F) (the C6F5 groups are not equivalent); 13C{1H} NMR
(100 MHz, CD2Cl2, 298 K): d=164.1 (s), 150.8 (s), 148.7 (m), 144.6 (s),
140.7 (m), 137.4 (m), 129.5 (s), 129.4 (s), 123.0 (s, br.), 121.0 (s), 21.7 (s),
11.4 ppm (s), the carbon atoms bonded to boron could not be observed;
elemental analysis calcd (%) for C29H11NOBF15·0.5 toluene: C 52.99, H
2.08, N 1.93; found: C 52.83, H 2.35, N 1.90; DART MS, m/z: 174.1
(5 mL) and was added to N-(prop-2-yn-1-yl)adamantane-1-carboxamide
(109 mg, 0.5 mmol) affording an orange solution. The reaction mixture
was heated to 458C for 2 h to give colourless needles of the product
(3o), which were washed with pentane (2ꢃ3 mL) and dried in vacuo
(203 mg, 56%, 0.28 mmol). 1H NMR (400 MHz, [D8]THF, 298 K): d=
11.16 (s, br., 1H, NH), 6.40 (s, br., 1H, C=CH), 4.01 (d, 4JHH =2.8 Hz,
2H, CH2), 2.09 (s, br., 3H, Ad), 2.00 (m, br., 6H, Ad), 1.80 ppm (m, br.,
6H, Ad); 11B NMR (128 MHz, [D8]THF, 298 K): d=ꢀ16.6 ppm (s);
19F NMR (377 MHz, [D8]THF, 298 K): d=ꢀ132.7 (d, 2F, JFF =21.5 Hz, o-
F), ꢀ163.5 (t, 3JFF =29.9 Hz, 1F, p-F), ꢀ167.2 ppm (m, br., 2F, m-F);
1
13C{1H} NMR (100 MHz, [D8]THF, 298 K): d=183.9 (s), 149.3 (m, JCF
=
1
1
(calcd for [(MꢀB
U
244 Hz), 146.2 (m), 139.5 (m, JCF =242 Hz), 137.6 (m, JCF =244 Hz), 46.6
(s), 38.5 (s), 37.6 (s), 36.7 (s), 28.5 ppm (s), the carbon atoms bonded to
boron could not be observed; elemental analysis calcd (%) for
C32H19NOBF15·0.5 toluene: C 54.99, H 3.00, N 1.92; found: C 54.52, H
3.34, N 1.83; DART MS, m/z: 730.1 (calcd for [(M+H]+: 730.1), 218.2
toluene (2 mL) and was added to 5-methyl-2-(p-tolyl)oxazole (17 mg,
0.1 mmol). The reaction mixture was left for 1 h without stirring. Slow
evaporation of the toluene solvent afforded colourless crystals of the
product (51 mg, 0.07 mmol, 74%). 1H NMR (400 MHz, [D8]toluene,
298 K): d=7.08 (d, 3JHH =8.4 Hz, 2H, o-H), 6.80 (m, br., 1H, C-H oxa-
zole), 6.54 (d, 3JHH =8.4 Hz, 2H, m-H), 1.85 (s, 3H, CH3), 1.51 ppm (s,
br., 3H, CH3); 19F NMR (377 MHz, [D8]toluene, 298 K): d=ꢀ129.6 (s,
(calcd for [(MꢀB
ACHTUNGTRENNUNG
Synthesis of 3p: B
AHCTUNGTRENNUNG
(4 mL) and was added to 2-phenyl-N-(prop-2-yn-1-yl)acetamide (69 mg,
0.4 mmol). The reaction mixture was heated to 458C for six days without
11936
www.chemeurj.org
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2013, 19, 11928 – 11938

Reactions of BACHTUNGTRENNUNG(C6F5)3 with Propargyl Amides
FULL PAPER
stirring. Removal of the solvent in vacuo afforded an oil that could be re-
crystallised from toluene/pentane. Removal of the remaining solvent by
pipette followed by washing with pentane (3ꢃ3 mL) and drying in vacuo
afforded the pure product (170 mg, 62%, 0.25 mmol). 1H NMR
(400 MHz, CD2Cl2, 298 K): d=7.87 (s, br., 1H, NH), 7.48 (m, 3H, Ar-H),
7.30 (m, 3H, Ar-H), 6.56 (s, 1H, -C=CH), 4.10 (s, 4H, CH2); 11B NMR
(128 MHz, CD2Cl2, 298 K): d=ꢀ17.0 ppm (s); 19F NMR (377 MHz,
out stirring. Removal of the solvent in vacuo afforded a yellow oil, which
was recrystallised from the layering of a hot, saturated solution with pen-
tane. The crystals were washed with pentane (3ꢃ3 mL) and dried in
vacuo to afford the pure product (104 mg, 0.15 mmol, 37%). 1H NMR
(500 MHz, CD2Cl2, 298 K): d=7.75 (m, 3JHH =7.9 Hz, 2H, o-H), 7.73 (tt,
3JHH =7.5 Hz, 4JHH =1.2 Hz, 1H, p-H), 7.56 (m, 2H, m-H), 7.53 (s, br.,
1H, NH), 6.14 (s, 1H, C=CH), 1.73 (s, 6H, CH3); 11B NMR (128 MHz,
CD2Cl2, 298 K): d=1.4 (s, br.); 19F NMR (377 MHz, CD2Cl2, 298 K): d=
CD2Cl2, 298 K): ꢀ133.2 (d, 2F, JFF =22.1 Hz, o-F), ꢀ161.9 (t, 1F, JFF
=
3
19.6 Hz, p-F), ꢀ166.1 ppm (m, 2F, m-F); 13C{1H} NMR (100 MHz,
CD2Cl2, 298 K): d=179.6 (s), 148.7 (m, 1JCF =240 Hz), 145.0 (m), 139.3
(m, 1JCF =249 Hz), 137.1 (m, 1JCF =251 Hz), 130.9 (s), 130.6 (s), 130.2 (s),
127.8 (s), 122.6 (m), 46.3 (s), 35.0 ppm (s), the signals due to the carbon
atoms bonded to boron in the C6F5 rings could not be observed; elemen-
tal analysis calcd (%) for C29H11NOBF15: C 50.83, H 1.62, N 2.04; found:
C 49.36, H 1.86, N 2.00; DART MS, m/z: 724.0 (calcd for [M+K]+:
724.0), 708.1 (calcd for [M+Na]+: 708.1), 703.1 (calcd for [M+NH4]+:
703.1), 686.1 ppm (calcd for [M+Na]+: 686.1).
ꢀ132.5 (m, 4F, o-F B
G
=
20 Hz, 2F, p-F B
(C6F5)2), ꢀ158.8 (t, 3JFF =21 Hz, 1F, p-F C6F5), ꢀ164.6
(m, 2F, m-F C6F5), ꢀ165.1 ppm (m, 4F, m-F C6F5); 13C{1H} NMR
(125 MHz, CD2Cl2, 298 K) partial: d=170.8 (s), 148.6 (m, 1JCF =248 Hz),
144.5 (m, 1JCF =248 Hz), 142.7 (s), 140.6 (m), 140.33 (m, 1JCF =248 Hz),
138.9–138.3 (m), 136.8–136.5 (m), 135.6 (s), 130.4 (s), 130.1 (s), 128.6 (s),
59.6 (s), 59.6 ppm (s); elemental analysis calcd (%) for C30H13NOBF15: C
51.53, H 1.87, N 2.00; found: C 51.35, H 2.17, N 2.05; DART MS, m/z:
700.1 (calcd for [(M+H]+: 700.1), 188.1 (calcd for [(MꢀB
(C6F5)3)+H]+:
ACHTUNGTRENNUNG
188.1).
Synthesis of 3q: BACHTUNGTRENNUNG(C6F5)3 (205 mg, 0.4 mmol) was dissolved in toluene
X-ray crystallography: Crystals were coated in paratone oil and mounted
in a cryoloop. Data were collected on Nonius Kappa CCD or Bruker
APEX2 X-ray diffractometers using graphite-monochromated MoKa radi-
ation (0.71073 ꢂ). The temperature was maintained at 150(2) K using an
Oxford cryostream cooler for both initial indexing and full data collec-
tion. Data were collected by using Bruker APEX-2 software and process-
ed using SAINT and an absorption correction applied using multi-scan
within the APEX-2 program.[23] The structures were solved by direct
methods within the SHELXTL package. All structures were refined
against F2 using the SHELXTL package.[24] Unit cell parameters and re-
finement statistics are presented in the Supporting Information.
(4 mL) and was added to N-(prop-2-yn-1-yl)pentanamide (56 mg,
0.4 mmol). The reaction mixture was heated to 458C for six days without
stirring, resulting in a pale yellow/orange solution. Removal of the sol-
vent in vacuo followed by recrystallisation from toluene/THF/pentane af-
forded colourless crystals of the product. Removal of the remaining sol-
vent by pipette followed by washing with pentane (3ꢃ3 mL) and drying
in vacuo afforded the pure product (142 mg, 54%, 0.22 mmol). 1H NMR
(400 MHz, CD2Cl2, 298 K): d=10.47 (s, br., 1H, NH), 6.47 (s, 1H,
3
-C=CH), 4.07 (s, br., 4H, CH2), 2.67 (t, JHH =7.8 Hz, 2H, CH2), 1.73 (m,
2H, CH2), 1.45 (m, 2H, CH2), 0.96 (t, 3JHH =7.3 Hz, 3H, CH3), one equiv-
alent of THF was also observed at 3.69 and 1.89 ppm; 11B NMR
(128 MHz, CD2Cl2, 298 K): d=ꢀ16.9 (s); 19F NMR (377 MHz, CD2Cl2,
298 K): ꢀ133.2 (d, 2F, JFF =22.5 Hz, o-F), ꢀ162.2 (t, 1F, JFF =20.6 Hz, p-
F), ꢀ166.3 ppm (m, 2F, m-F); 13C{1H} NMR (100 MHz, CD2Cl2, 298 K):
CCDC-939515, CCDC-939516, CCDC-939517, CCDC-939518, CCDC-
939519, CCDC-939520, CCDC-939521, CCDC-939522, CCDC-939523,
CCDC-939524, CCDC-939525 and CCDC-939526 contain the supplemen-
tary crystallographic data for this paper. These data can be obtained free
of charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
1
1
d=179.8 (s), 148.8 (m, JCF =239 Hz), 144.8 (m), 139.1 (m, JCF =248 Hz),
1
138.6 (s, toluene), 137.3 (m, JCF =246 Hz), 129.6 (s, toluene), 128.7 (s, tol-
uene), 125.8 (s, toluene), 121.0 (m), 68.7 (s, THF), 46.2 (s), 28.1 (s), 27.0
(s), 26.0 (s, THF), 22. (s), 21.7 (s, toluene), 13.6 ppm (s), the signals due
to the carbon atoms bonded to boron in the C6F5 rings could not be ob-
served; elemental analysis calcd (%) for C26H13NOBF15.tol: C 51.72, H
3.33, N 1.84; found: C 49.82, H 2.93, N 1.94; ESI+ MS, m/z: 690.0 (calcd
for [M+K]+: 690.0), 669.1 (calcd for [M+NH4]+: 669.1).
Acknowledgements
Synthesis of 5-methyl-2-(p-tolyl)oxazole, 5l: 4-Methyl-N-(prop-2-yn-1-yl)-
benzamide (407 mg, 2.35 mmol) was dissolved in CH2Cl2 (8 mL) and
5 mol% AuCl3 added (36 mg, 0.2 mmol, 0.05 equiv). The resulting solu-
tion was stirred at room temperature for 6 h. The crude product was puri-
fied by column chromatography (hexanes:EtOAc=9:1 to 4:1) to give the
pure oxazole as a colourless liquid (290 mg, 1.67 mmol, 71%). Rf =0.34
(hexanes:EtOAc=4:1) whose NMR spectra were comparable to those
reported previously.[7] 1H NMR (400 MHz, CDCl3, 298 K): d=7.89 (d,
3JHH =8.1 Hz, 2H, o-H), 7.24 (d, 3JHH =8.1 Hz, 2H, m-H), 6.81 (s, br.,
2H, C-H oxazole), 2.39 (s, 3H, CH3), 2.38 ppm (s, br., 3H, CH3);
1H NMR (400 MHz, [D8]toluene, 298 K): d=7.89 (d, 3JHH =8.2 Hz, 2H,
o-H), 6.94 (d, 3JHH =8.2 Hz, 2H, m-H), 6.64 (m, br., 2H, C-H oxazole),
NSERC of Canada is thanked for financial support. D.W.S. is grateful for
the award of a Canada Research Chair. M.M.H. is grateful to the Fonds
der chemischen Industrie for a Chemiefonds scholarship and the Studien-
stiftung des deutschen Volkes. We would also like to acknowledge Profes-
sor Mark Lautens for support of M.M.H. at the University of Toronto.
[1] a) Y. Kato, N. Fusetani, S. Matsunaga, K. Hashimoto, S. Fujita, T.
Furuya, J. Am. Chem. Soc. 1986, 108, 2780–2781; b) S. Carmeli,
R. E. Moore, G. M. L. Patterson, T. H. Corbett, F. A. Valeriote, J.
Am. Chem. Soc. 1990, 112, 8195–8197; c) G. Pattenden, J. Hetero-
cycl. Chem. 1992, 29, 607–618; d) P. Brown, D. J. Best, N. J. P.
Broom, R. Cassels, P. J. OꢄHanlon, T. J. Mitchell, N. F. Osborne,
J. M. Wilson, J. Med. Chem. 1997, 40, 2563–2570; e) D. K. Dalvie,
A. S. Kalgutkar, S. C. Khojasteh-Bakht, R. S. Obach, J. P. OꢄDonnell,
Chem. Res. Toxicol. 2002, 15, 269–299.
[2] a) R. Lakhan, B. Ternai, Adv. Heterocycl. Chem. 1974, 17, 99–211;
b) S. Lang-Fugmann, Methoden der Organischen Chemie (Ed.: E.
Schaumann), Houben-Weyl, Thieme, Stuttgart, Germany, 1993;
c) D. C. Palmer, S. Venkatraman, The Chemistry of Heterocyclic
Compounds, A Series of Monographs, Oxazoles: Synthesis Reactions
and Spectroscopy, Part A (Ed.: D. C. Palmer), Wiley, New York,
2003.
4
2.04 (s, 3H, CH3), 1.89 ppm (d, JHH =1.2 Hz, 3H, CH3).
Synthesis of 2-(adamantan-1-yl)-5-methyloxazole (5o): BACHTUNRGTNEUNG(C6F5)3 (25 mg,
0.05 mmol) was dissolved in toluene (10 mL) and was added to N-(prop-
2-yn-1-yl)adamantane-1-carboxamide (109 mg, 0.5 mmol). The reaction
mixture was heated to 1008C for 10 days without stirring. The product
was purified by column chromatography (80:20 hexanes:EtOAc) to give
1
the pure product as an off-white oil (90.6 mg, 0.42 mmol, 83%) whose H
and 13C NMR shifts were comparable to those reported previously.[7b] Rf
(hexanes:EtOAc=80:20)=0.33; 1H NMR (400 MHz, CDCl3, 298 K): d=
6.58 (d, 4JHH =1.2 Hz, 1H, oxazole -H), 2.27 (d, 4JHH =1.2 Hz, 3H, CH3),
2.06 (br. s, 3H, Ad-H), 2.01 (m, 6H, Ad-H), 1.76 ppm (br. s, 6H, Ad-H);
13C{1H} NMR (100 MHz, CDCl3, 298 K): d=170.0 (s), 147.7 (s), 122.1 (s),
40.6 (s), 36.7 (s), 35.6 (s), 20.2 (s), 11.0 ppm (s).
[3] a) H. Nishiyama, H. Sakaguchi, T. Nakamura, M. Horihata, M.
Kondo, K. Itoh, Organometallics 1989, 8, 846–848; b) H. Nishiyama,
S.-B. Park, K. Itoh, Tetrahedron: Asymmetry 1992, 3, 1029–1034;
c) A. Gissibl, M. G. Finn, O. Reiser, Org. Lett. 2005, 7, 2325–2328.
[4] H. Vorbrꢅggen, K. Krolikiewicz, Tetrahedron 1993, 49, 9353–9372.
Synthesis of 7r: BACHTUNGTRENNUNG(C6F5)3 (205 mg, 0.4 mmol) was dissolved in toluene
(3 mL) and was added to N-(2-methylbut-3-yn-2-yl)benzamide (75 mg,
0.4 mmol). The reaction mixture was heated to 458C for four days with-
Chem. Eur. J. 2013, 19, 11928 – 11938
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
11937

D. W. Stephan et al.
[5] a) A. Arcadi, S. Cacchi, L. Cascia, G. Fabrizi, F. Marinelli, Org. Lett.
2001, 3, 2501–2504; b) A. Bacchi, M. Costa, B. Gabriele, G. Pelizzi,
G. Salerno, J. Org. Chem. 2002, 67, 4450–4457; c) A. Bacchi, M.
Costa, N. Della Ca, B. Gabriele, G. Salerno, S. Cassoni, J. Org.
Chem. 2005, 70, 4971–4979; d) E. M. Beccalli, E. Borsini, G. Broggi-
ni, G. Palmisano, S. Sottocornola, J. Org. Chem. 2008, 73, 4746–
4749; e) A. Saito, K. Iimura, Y. Hanzawa, Tetrahedron Lett. 2010,
51, 1471–1474; f) N. T. Patil, ChemCatChem 2011, 3, 1121–1125;
g) N. T. Patil, R. D. Kavthe, V. S. Shinde, Tetrahedron 2012, 68,
8079–8146.
Frçhlich, B. Schirmer, S. Grimme, G. Erker, Angew. Chem. 2010,
122, 2464–2467; Angew. Chem. Int. Ed. 2010, 49, 2414–2427; d) C.
Chen, F. Eweiner, B. Wibbeling, R. Frçhlich, S. Senda, Y. Ohki, K.
Tatsumi, S. Grimme, G. Kehr, G. Erker, Chem. Asian J. 2010, 5,
2199–2208; e) M. A. Dureen, C. C. Brown, D. W. Stephan, Organo-
metallics 2010, 29, 6594–6607; f) D. Winkelhaus, B. Neumann, H.-G.
Stammler, N. W. Mitzel, Dalton Trans. 2012, 41, 9143–9150.
[12] T. Voss, C. Chen, G. Kehr, E. Nauha, G. Erker, D. W. Stephan,
Chem. Eur. J. 2010, 16, 3005–3008.
[13] For 1,1-carboboration reactions see: a) C. Chen, G. Kehr, R. Frçh-
lich, G. Erker, J. Am. Chem. Soc. 2010, 132, 13594–13595; b) O.
Ekkert, G. Kehr, R. Frçhlich, G. Erker, J. Am. Chem. Soc. 2011,
133, 4610–4616; c) C. Chen, T. Voss, R. Frçhlich, G. Kehr, G. Erker,
Org. Lett. 2011, 13, 62–65; d) J. Mçbus, Q. Bonnin, K. Ueda, R.
Frçhlich, K. Itami, G. Kehr, G. Erker, Angew. Chem. Int. Ed. 2012,
124, 1990–1993; Angew. Chem. Int. Ed. 2012, 51, 1954–1957; e) G.
Kehr, G. Erker, Chem. Commun. 2012, 48, 1839–1850, and referen-
ces therein; f) C. Eller, G. Kehr, C. G. Daniliuc, R. Frçhlich, G.
Erker, Organometallics 2013, 32, 384–386.
[6] M. Harmata, C. Huang, Synlett 2008, 1399–1401.
[7] a) A. S. K. Hashmi, J. P. Weyrauch, W. Frey, J. W. Bats, Org. Lett.
2004, 6, 4391–4394; b) M. D. Milton, Y. Inada, Y. Nishibayashi, S.
Uemura, Chem. Commun. 2004, 2712–2713; c) A. S. K. Hashmi, M.
Rudolph, S. Schymura, J. Visus, W. Frey, Eur. J. Org. Chem. 2006,
4905–4909; d) D. Aguilar, M. Contel, R. Navarro, T. Soler, E. P. Ur-
riolabeitia, J. Organomet. Chem. 2009, 694, 486–493; e) A. S. K.
Hashmi, A. M. Schuster, F. Rominger, Angew. Chem. 2009, 121,
8396–8398; Angew. Chem. Int. Ed. 2009, 48, 8247–8249; f) J. P.
Weyrauch, A. S. K. Hashmi, A. Schuster, T. Hengst, S. Schetter, A.
Littmann, M. Rudolph, M. Hamzic, J. Visus, F. Rominger, W. Frey,
J. W. Bats, Chem. Eur. J. 2010, 16, 956–963; g) A. S. K. Hashmi, L.
Molinari, F. Rominger, T. Oeser, Eur. J. Org. Chem. 2011, 2256–
2264; h) A. S. K. Hashmi, A. M. Schuster, M. Schmuck, F. Roming-
er, Eur. J. Org. Chem. 2011, 4595–4602; i) O. A. Egorova, H. Seo, Y.
Kim, D. Moon, Y. M. Rhee, K. H. Ahn, Angew. Chem. 2011, 123,
11648–11652; Angew. Chem. Int. Ed. 2011, 50, 11446–11450.
[8] a) H. C. Brown, Organic Synthesis via Boranes, Wiley, New York,
1975; b) B. M. Mikhailov, Y. N. Bubnov, Organoboron Compounds
in Organic Synthesis, Harwood Academic, New York, 1984; c) A.
Pelter, K. Smith, H. C. Brown, Borane Reagents, Academic Press
Limited, London, 1988; d) D. G. Hall, Boronic Acids, 2.ed. Wiley-
VCH, Weinheim, 2011.
[14] For the use of electrophilic halogen reagents in the intramolecular
cyclisation reactions of amides and alkynes, see: S. Mehta, T. Yao,
R. C. Larock, J. Org. Chem. 2012, 77, 10938–10944; C. Schlemmer,
L. Andernach, D. Schollmeyer, B. F. Straub, T. Opatz, J. Org. Chem.
2012, 77, 10118–10124.
[15] See also the Supporting Information.
[16] S. Punna, S. Meunier, M. G. Finn, Org. Lett. 2004, 6, 2777–2779.
[17] K. Jayaprakash, C. S. Venkatachalam, K. K. Balasubramanian, Tetra-
hedron Lett. 1999, 40, 6493–6496.
[18] C. L. Allen, B. N. Atkinson, J. M. J. Williams, Angew. Chem. 2012,
124, 1412–1415; Angew. Chem. Int. Ed. 2012, 51, 1383–1386.
[19] X. Meng, S. Kim, Org. Biomol. Chem. 2011, 9, 4429–4431.
[20] G. C. Senadi, W.-P. Hu, J.-S. Hsiao, J. K. Vandavasi, C.-Y. Chen, J.-J.
Wang, Org. Lett. 2012, 14, 4478–4481.
[9] G. C. Welch, R. R. San Juan, J. D. Masuda, D. W. Stephan, Science
2006, 314, 1124–1126.
[21] S. Yasuhara, M. Sasa, T. Kusakabe, H. Takayama, M. Kimura, T.
Mochida, K. Kato, Angew. Chem. 2011, 123, 3998–4001; Angew.
Chem. Int. Ed. 2011, 50, 3912–3915.
[22] J. Deng, J. Tabei, M. Shiotsuki, F. Sanda, T. Masuda, Macromole-
cules 2004, 37, 1891–1896.
[23] APEX2 and SAINT software; Bruker AXS Inc., Madison, Wiscon-
sin, USA.
[24] SHELXTL, Bruker AXS Inc., Madison, Wisconsin, USA.
[10] For recent reviews see: a) D. W. Stephan, Org. Biomol. Chem. 2008,
6, 1535–1539; b) D. W. Stephan, Dalton Trans. 2009, 3129–3136;
c) D. W. Stephan, Chem. Commun. 2010, 46, 8526–8533; d) D. W.
Stephan, G. Erker, Angew. Chem. 2010, 122, 50–81; Angew. Chem.
Int. Ed. 2010, 49, 46–76; e) D. W. Stephan, Org. Biomol. Chem.
2012, 10, 5740–5746.
[11] a) M. A. Dureen, D. W. Stephan, J. Am. Chem. Soc. 2009, 131,
8396–8397; b) C. Jiang, O. Blacque, H. Berke, Organometallics
2010, 29, 125–133; c) C. M. Mçmming, G. Kehr, B. Wibbeling, R.
Received: May 16, 2013
Published online: August 6, 2013
11938
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Chem. Eur. J. 2013, 19, 11928 – 11938