Synthesis of phosphaguanidines by hydrophosphination of carbodiimides with phosphine boranes

Article abstract of DOI:10.1021/jo501841s

The direct addition of anionic secondary phosphine boranes to carbodiimides yields both chiral and achiral phosphaguanidine boranes under ambient temperature conditions. An analogous preparation of menthol-derived phosphinite boranes is also described. These products can be deborinated to give the corresponding phosphines, and subsequently oxidized to give phosphine oxides. The robustness of this method was further demonstrated in the synthesis of structurally novel cyclic phosphaguanidines. (Chemical Equation Presented).

Full text of DOI:10.1021/jo501841s

Note
pubs.acs.org/joc
Synthesis of Phosphaguanidines by Hydrophosphination of
Carbodiimides with Phosphine Boranes
Carl A. Busacca,*,† John A. Milligan,§ Eakkaphon Rattanangkool,§ Cyrus Ramavarapu,†,§ Anji Chen,‡
Anjan K. Saha,† Zhibin Li,† Heewon Lee,† Steven J. Geib,§ Guijun Wang,‡ Chris H. Senanayake,†
and Peter Wipf*,§
†Chemical Development, Boehringer-Ingelheim Pharmaceuticals, Inc., 900 Ridgebury Road, Ridgefield, Connecticut 06877, United
States
‡Department of Chemistry and Biochemistry, Old Dominion University, 4541 Hampton Boulevard, Norfolk, Virginia 23529, United
States
§Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States
S
* Supporting Information
ABSTRACT: The direct addition of anionic secondary
phosphine boranes to carbodiimides yields both chiral and
achiral phosphaguanidine boranes under ambient temperature
conditions. An analogous preparation of menthol-derived
phosphinite boranes is also described. These products can be
deborinated to give the corresponding phosphines, and
subsequently oxidized to give phosphine oxides. The robust-
ness of this method was further demonstrated in the synthesis of structurally novel cyclic phosphaguanidines.
raphy on SiO2 afforded the desired phosphaguanidine boranes
he preparation of novel phosphines has been facilitated by
Tan increasing number of methods for the hydro- (Figure 1.)
phosphonation of carbon−carbon multiple bonds.1 While
many hydrophosphinations exhibit high levels of efficiency
and selectivity, most use secondary phosphines that are prone
to oxidation or spontaneous combustion. Our research team
has taken interest in using phosphine boranes as air-stable,
robust alternatives to secondary phosphines in hydrophosphi-
nations.2 Although other catalytic and thermal stoichiometric
hydrophosphinations with phosphine boranes have been
reported,3 we have found that a secondary phosphine borane
undergoes a base-mediated hydrophosphination with unac-
tivated alkynes, allenyl phosphine oxides, propargylic alcohols,
and propargylic amines.4 These findings prompted us to further
investigate the scope of this straightforward hydrophosphina-
tion procedure, and we now report that N-alkyl and N-aryl
carbodiimides, including strained medium ring derivatives, are
also competent substrates for this reaction. The resulting
phosphaguanidines are of considerable interest as ligands for
transition metals and as precursors for metallacycles.5
Despite the fact that substoichiometric amounts of alkali-
metal bases can effect hydrophosphinations of carbodiimides
with secondary phosphines,5 we opted to utilize our previously
optimized conditions for alkyne hydrophosphinations on
account of method generality. Accordingly, a dimethylaceta-
mide solution of phosphine borane and carbodiimide (1.2:1
ratio) was sparged with argon to guard against oxidative
formation of a phosphinous acid-borane. Treatment of this
solution with NaH dispersion, followed by air oxidation of the
excess borane phosphide, aqueous workup, and chromatog-
The reaction was general with regard to carbodiimide
substitution, as both aryl and alkyl substituents are tolerated
(including commercially available DCC). Electron-rich aryl,
electron-poor aryl, and alkyl phosphine boranes are all suitable
substrates (1−8). In addition, both aliphatic and aromatic
phosphine boranes can be used for the hydrophosphination
(9−15). For the P-dicyclohexyl derivates, a mixture of Esyn and
Zsyn conformers was observed, as previously described for
phosphaguanidines.6 The structures of 4 and 5 were confirmed
by X-ray crystal structure analysis. In the solid state, both 4 and
5 assumed the Zsyn conformation, as expected.6 To the best of
our knowledge, this is the first general hydrophosphination of
carbodiimides with phosphine boranes and represents a
versatile alternative to catalytic hydrophosphinations of
carbodiimides with secondary phosphines.7
After these encouraging preliminary results, we were
interested to explore the use of chiral carbodiimides as a
means to prepare enantiomerically enriched phosphaguanidines
for potential future use of these products as ligands in
asymmetric catalysis. Thus, commercially available (R)-2-
aminoethylbenzene was used to prepare a chiral carbodiimide
via the corresponding thiourea. The yields for the subsequent
hydrophosphinations were generally comparable to other
examples (Figure 1, 9−12, 15), and since the stereogenic
carbons on the amine substituents are unaffected by the
Received: August 8, 2014
Published: September 19, 2014
© 2014 American Chemical Society
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Figure 1. Phosphaguanidine boranes prepared by NaH-mediated hydrophosphination of carbodiimides.
hydrophosphinations, the resulting phosphaguanidine boranes
are stereochemically pure.
decomplexation at mildly elevated temperature under retention
of configuration.8 These conditions performed well on aromatic
phosphine boranes to give phosphaguanidines 19 and 20
(Scheme 2). While the NMR spectra of 19 and 20 were slightly
Another approach toward chiral phosphaguanidines is the
use of a chiral phosphine or phosphinite derivative as the
hydrophosphination reagent. Menthol-derived phosphinites
have previously been used for similar purposes,8 and 16 was
prepared from menthol and PhPCl2, followed by boron
complexation (BH3/THF) and LiBH4 reduction according to
a literature procedure.8
Scheme 2. P-Deprotection of Phosphine Boranes 13 and 14
to Phosphaguanidines 19 and 20
Repeated recrystallizations of a 52:48 RP:SP mixture of
diastereomers of 16 obtained in 28% yield afforded the RP
diastereomer of 16 as a white crystalline solid.8 While the
carbodiimide hydrophosphination of this substrate with NaH
led to significant decomposition, using n-BuLi as the base
provided 17 and 18 in low to moderate yields (Scheme 1). The
hydrophosphination with 16 proceeds with retention of
configuration at the phosphorus center.1g,8,9
With a general route to both chiral and achiral
phosphaguanidines established, we investigated protocols for
removing the borane to generate more nucleophilic phosphine
reagents and hence potentially more active catalysts. Toward
this end, 1,4-diazabicyclo[2.2.2]octane (DABCO) was used for
Scheme 1. Chiral Phosphinite Boranes Prepared by n-BuLi-
Mediated Hydrophosphination of Carbodiimides
broadened, only one major diastereomer was visible, and in
accordance to the literaure data, these compounds were
assigned as the Esyn isomers.6 Alcoholysis10 of phosphane
boranes represents an alternative deprotection procedure, but
the DABCO method proved to be more general in our hands.
We also explored Denmark and Werner’s modification of
Netherton and Fu’s protocol to convert the more sensitive
phosphine boranes to their tetrafluoroborate salts.11 Surpris-
ingly, treatment of 1 with HBF4 did not cleave the phosphine
borane, and the reaction stopped at the N-protonated
phosphaguanidine tetrafluoroborate salt 21 (Scheme 3). The
structure of 21 was secured by X-ray analysis and showed one
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of the cyclohexyl groups positioned syn and the second anti to
the phosphorus atom of the phosphazene.12
Scheme 5. Synthesis and P-Deprotection of Cyclic
Phosphaguanidines
Scheme 3. Conversion of Phosphaguanidine Borane 1 to the
Tetrafluoroborate salt 21
For a proof-of-principle study, conversion of phosphaguani-
dine 19 to the phosphine oxide 22 was accomplished in nearly
quantitative yield by treatment with hydrogen peroxide, while
previously reported oxidants such as t-butyl hydrogen peroxide
and mCPBA resulted in the formation of multiple oxidation
products (Scheme 4).12
Scheme 4. Formation of Phosphaguanidine Oxide 22
Since some of the phosphaguanidines demonstrated geo-
metric Esyn/Zsyn isomerism, we sought to restrict the flexibility
of the amidine substructure by embedding it into a medium
ring system. We also surmised that, in a cyclic phosphaguani-
dine, the phosphorus atom would be less sterically encumbered
and thus more conducive for transition metal or nucleophilic
catalysis. Although the requisite cyclic carbodiimides are
relatively rare, we were pleased to find that Molina et al. had
reported an expedient synthesis of carbodiimide 23 in three
steps from a commercially available dianiline (Scheme 5).13
Hydrophosphination of 23 under standard conditions resulted
in phosphaguanidine boranes 24−27 in 67−86% yield.
Deprotection of 25−27 with DABCO provided the corre-
sponding phosphaguanidines 28−30 in 65−94% yield, and 29
was further oxidized to phosphine oxide 31 in good yield. A
single-crystal X-ray analysis of 24 showed a nearly coplanar
alignment of C−N bonds leading to the aromatic rings, with a
distance of only 3.04 Å between the two phenyl carbon atoms
attached to the phosphaguanidine (Figure 2). Similarly, the
ethylene bridge was in an eclipsed conformation with a dihedral
angle of 22.0°, forming a compact boatlike nine-membered ring
with the guanidine bridge. The juxtaposition of the benzene
rings in 24 is reminiscent of a paracyclophane; the distances
between opposing carbon atoms vary from 2.8 to 5.1 Å, with an
average of 4.0 Å (Figure 2). In comparison, the inter-ring
distances in [2,2]paracyclophane and graphite are 3.1 and 3.4
Å, respectively.14
Figure 2. Structure of 24 with selected bond distances and dihedral
angles; only the heteroatom−hydrogen bonds are shown.
cleaved to afford phosphaguanidines, and in order to
demonstrate the feasibility for this transformation, we also
generated two phosphaguanidine oxides by oxidation with
hydrogen peroxide. Phosphaguanidines and the corresponding
P-oxides are of potential utility as ligands in transition metal
catalysis and organocatalysis.15
In summary, we have developed a straightforward general
method for the direct hydrophosphination of carbodiimides
with secondary phosphine boranes to afford air-stable
phosphaguanidine boranes. For the first time, cyclic phospha-
guanidines were prepared by hydrophosphination of a nine-
membered cyclic carbodiimide. The borane complexes can be
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plug of SiO2 eluting with CH2Cl2. The filtrate was concentrated under
reduced pressure and purified by chromatography on SiO2 (hexanes)
under N2 pressure to afford S5 (0.700 g, 3.58 mmol, 82%) as an oil:
1H NMR (500 MHz, CDCl3) δ 7.35−7.30 (m, 4 H), 7.20−7.15 (m, 6
H); 13C NMR (125 MHz, CDCl3) δ 138.5 (s), 135.3 (s), 129.5 (d),
125.6 (d), 124.2 (d); HRMS m/z calcd for C13H11N2 [M + H]+
195.0917, found 195.0903.
N-Phenyl,N′-cyclohexylcarbodiimide (S6). Prepared according to
General Procedure C from N-phenyl,N-cyclohexylthiourea (3.00 g,
12.8 mmol, 1.00 equiv), DMAP (0.064 g, 0.52 mmol, 4.0 mol %), and
Et3N (5.4 mL, 38.4 mmol, 3.00 equiv) in CH2Cl2 (45 mL) and
purified by chromatography on SiO2 under N2 pressure (20:1
hexanes/EtOAc) to give S6 (1.21 g, 6.02 mmol, 47%) as a pale
yellow oil: 1H NMR (500 MHz, CDCl3) δ 7.32−7.27 (m, 2 H), 7.14−
7.11 (m, 3 H), 3.53−3.45 (m, 1 H), 2.07−2.03 (m, 2 H), 1.83−1.76
(m, 2 H), 1.64−1.25 (m, 6 H); 13C NMR (125 MHz, CDCl3) δ 140.9
(s), 136.1 (s), 129.3 (d), 124.5 (d), 123.3 (d), 56.6 (d), 34.9 (t), 26.9
(t), 25.3 (t), 24.3 (t); HRMS m/z calcd for C13H17N2 [M + H]+
201.1321, found 201.1340.
N-(3,5-Bistrifluoromethyl)phenyl N′-Cyclohexylcarbodiimide (S7).
Prepared according to General Procedure C from thiourea S1 (0.26 g,
0.71 mmol), triethylamine (0.30 mL, 1.4 mmol, 2.0 equiv), mesyl
chloride (0.10 mL, 1.4 mmol, 2.0 equiv), and DMAP (0.004 g, 0.03
mmol, 5 mol %) in CH2Cl2 (5 mL) and purified by chromatography
on SiO2 (5% EtOAc/hexanes) to afford S7 (0.197 g, 0.585 mmol,
77%) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ 7.56 (s, 1 H),
7.46 (s, 2 H), 3.63−3.58 (m, 1 H), 2.03−2.00 (m, 2 H), 1.77 (dd, 2 H,
J = 9.6, 4.0 Hz), 1.60−1.49 (m, 3 H), 1.43−1.40 (m, 3 H); 13C NMR
(100 MHz, CDCl3) δ 143.8, 133.2, 132.9, 132.5, 132.3, 132.2, 123.4
(q, 1JCF = 271 Hz), 123.2, 117.6 (q, J = 40 Hz), 56.8, 34.7, 25.2, 24.1;
HRMS m/z calcd for C15H15N2F6 [M + H]+ 337.1139, found
337.1141.
EXPERIMENTAL SECTION
■
General Methods. All reagents were used as received unless stated
otherwise. The phosphine boranes utilized herein as well as
phenylcyclohexyl thiourea were purchased and used as received.
Caution! All free secondary phosphines are pyrophoric and they should be
handled with care. All of the deprotonations with NaH described below
cause gas evolution (H2) and foaming to various degrees. It is, therefore,
best to use a large flask or reactor to contain the foams that are generated.
Accurate mass measurements were performed on a Time-of-Flight
mass spectrometer (LC/MSD TOF) operating in a positive
electrospray ionization mode with the capillary voltage of 3 kV. The
mass spectrometer was tuned and calibrated using a tuning mix prior
to sample analysis. Samples were introduced to the mass spectrometer
by flow injection using an HPLC system.
General Procedure A: Synthesis of Thioureas from Iso-
thiocyanates. N-(3,5-Bistrifluoromethyl)phenyl N′-Cyclohexyl-
thiourea (S1).16 A solution of 3,5-trifluoromethylphenyl isothiocya-
nate (0.18 mL, 1.0 mmol, 1.0 equiv) and cyclohexylamine (0.12 mL,
1.1 mmol, 1.1 equiv) in CH2Cl2 (5 mL) was stirred at rt overnight,
resulting in a cloudy solution. The mixture was concentrated and the
crude residue was purified by chromatography on SiO2 (1% MeOH in
CH2Cl2) to afford S1 (0.327 g, 0.883 mmol, 88%) as a colorless solid:
mp 164.1−165.8 °C; 1H NMR (300 MHz, acetone-d6) δ 8.34 (s, 2 H),
7.71 (s, 1 H), 4.31−4.27 (m, 1 H), 1.85−1.20 (m, 10 H).
N-4-Methoxyphenyl N′-Phenylthiourea (S2).17 Prepared according
to General Procedure A from phenyl isothiocyanate (1.128 g, 8.34
mmol) and p-anisidine (1.02 g, 8.34 mmol) in CH2Cl2 and purified by
recrystallization from EtOH/acetone (1:1) to afford S2 (1.63 g, 6.31
1
mmol, 76%) as a colorless solid: mp 155.3−156.9 °C; H NMR (300
MHz, acetone-d6) δ 8.94−8.83 (br s, 1 H), 7.58−7.53 (m, 2 H), 7.42−
7.32 (m, 4 H), 7.35−7.32 (m, 1 H), 6.94 (t, 2 H, J = 8.7 Hz), 3.82 (s, 3
H).
N-4-Methoxyphenyl N′-Phenylcarbodiimide (S8).18 Prepared
according to General Procedure C from thiourea S2 (1.63 g, 6.31
mmol), triethylamine (2.66 mL, 18.9 mmol, 3.00 equiv), mesyl
chloride (0.97 mL, 13 mmol, 2.0 equiv), and DMAP (0.039 g, 0.32
mmol, 5 mol %) in CH2Cl2 (60 mL) and purified by chromatography
on SiO2 (5% EtOAc/hexanes) to afford S8 (1.23 g, 5.49 mmol, 87%)
as a colorless oil: 1H NMR (300 MHz, CDCl3) δ 7.35−7.30 (m, 2 H),
7.19−7.13 (m, 5 H), 6.85 (dd, 2 H, J = 6.9, 2.4 Hz), 3.80 (s, 3 H).
N,N′-(R)-(+)-Methylbenzylcarbodiimide (S9). Prepared according
to General Procedure C from thiourea S3 (2.00 g, 7.03 mmol), DMAP
(0.040 g, 0.32 mmol, 5.0 mol %), triethylamine (2.94 mL 21.1 mmol,
3.00 equiv), and mesyl chloride (1.09 mL, 14.1 mmol, 2.00 equiv), in
dry CH2Cl2 (55 mL) and purified by chromatography on SiO2 (10%
EtOAc/Hex) under N2 pressure to afford S9 (1.20 g, 4.78 mmol, 68%,
General Procedure B: Synthesis of Thiourea Starting
Materials from Carbon Disulfide. N,N′-(R)-(+)-Methylbenzylth-
iourea (S3). Caution! STENCH. To a 500 mL three-neck round-
bottom flask were added carbon disulfide (6.62 mL, 110 mmol, 1.00
equiv), EtOH (300 mL), and (R)-methylbenzylamine (28 mL, 220
mmol, 2 equiv). The reaction mixture was allowed to stir under reflux
(∼88 °C) for 24 h and cooled to ∼5 °C, and the resultant voluminous
precipitate was filtered (Caution! STENCH). The flilter cake was
slurried in 100 mL of hexanes and then refiltered, and the solids were
air-dried on the frit for 30 min to afford S3 (23.1 g, 81.3 mmol, 74%)
as colorless needles: mp 200 °C; 1H NMR (400 MHz, CDCl3) δ 7.22
(s, 6 H), 7.13−6.87 (bs, 4 H), 6.07−5.87 (bs, 1 H), 5.12−4.88 (bs, 1
H), 1.47 (d, J = 6.4 Hz, 6 H); 13C NMR (100 MHz, CDCl3) δ 180.1
(s), 142.3 (s), 128.9 (d), 127.6 (d), 125.7 (d), 54.1 (d), 23.1 (q);
HRMS m/z calcd for C17H21N2S [M + H]+ 285.1420, found 285.1406.
The filtrates were deodorized with bleach before disposal.
1
yield adjusted to reflect residual cyclohexane) as a pale yellow oil: H
NMR (500 MHz, CDCl3) δ 7.32−7.29 (m, 4 H), 7.26−7.22 (m, 6 H),
4.54 (q, 2 H, J = 7.0 Hz), 1.45 (d, 6 H, J = 6.6 Hz); 13C NMR (125
MHz, CDCl3) δ 143.6 (s), 140.3 (s), 128.5 (d), 127.3 (d), 125.9 (d),
56.7 (d), 26.9 (t, C6H12), 24.6 (q); HRMS m/z calcd for C17H19N2 [M
+ H]+ 251.1543, found 251.1547.
N,N′-(R)-(−)-1-Cyclohexylethylthiourea (S4). Prepared according
to General Procedure B from carbon disulfide (3.5 mL, 59 mmol, 1.0
equiv), (R)-(−)-1-cyclohexylethylamine (15.0 g, 118 mmol, 2.00
equiv), and abs. EtOH (215 mL). The crude material was thoroughly
washed with hexanes and subsequently air-dried on the frit for ca. 1 h
to give S4 (9.10 g, 30.7 mmol, 52%) as a colorless, crystalline solid: mp
N,N′-(R)-(−)-1-Cyclohexylethylcarbodiimide (S10). Prepared ac-
cording to General Procedure C from thiourea S4 (5.00 g, 16.9
mmol), DMAP (0.089 g, 0.73 mmol, 4 mol %), triethylamine (7.0 mL,
51, mmol, 3.0 equiv), and mesyl chloride (2.60 mL, 33.8 mmol, 2.0
equiv) in CH2Cl2 (175 mL), and purified by chromatography on SiO2
(20:1 hexanes/EtOAc) to give S10 (2.13 g, 8.09 mmol, 49%, yield
adjusted to reflect residual cyclohexane) as a pale yellow oil: 1H NMR
(500 MHz, CDCl3) δ 3.21 (pent, 2 H, J = 6 Hz), 1.85−1.79 (m, 2 H),
1.77−1.74 (m, 4 H), 1.69−1.62 (m, 4 H), 1.32−0.93 (m, 12 H), 1.20
(d, 6 H, J = 6 Hz); 13C NMR (125 MHz, CDCl3) δ 139.7 (s), 58.3
(d), 44.4 (d), 29.4 (t), 28.9 (t), 26.4 (t), 26.2 (t), 26.1 (t), 19.7 (q);
HRMS m/z calcd for C17H31N2 [M + H]+ 263.2482, found 263.2464.
General Procedure D: Hydrophosphination of Carbodii-
mides. (N,N′-Dicyclohexylcarbamimidoyl)-dicyclohexylphosphine
Borane (1). A 100 mL three-neck flask equipped with a direct Ar
line, inert gas valve, and septum was charged with DCC (1.00 g, 4.85
mmol), dicyclohexylphosphine borane (1.03 g, 4.85 mmol, 1.00
equiv), and dry dimethylacetamide (12 mL), in that order. Argon was
1
181 °C; H NMR (500 MHz, CDCl3) δ 5.55 (bs, 1 H), 3.92 (br s, 1
H), 1.81−1.76 (m, 5 H), 1.72−1.65 (m, 4 H), 1.49−1.41 (m, 2 H),
1.29−0.95 (m, 8 H), 1.16 (d, J = 6.5 Hz, 6 H); 13C NMR (125 MHz,
CDCl3) δ 180.0 (s), 54.6 (d), 43.2 (d), 29.4 (t), 28.9 (t), 26.4 (t), 26.2
(t), 26.1 (t), 17.5 (q); HRMS m/z calcd for C17H33N2S [M + H]+
297.2359, found 297.2344. The filtrates were deodorized with bleach
before disposal.
General Procedure C: Preparation of Carbodiimides from
Thioureas. N,N′-Diphenylcarbodiimide (S5). To a 100 mL three-
neck flask equipped with an inert gas valve were added diphenyl
thiourea (1.00 g, 4.38 mmol, 1.00 equiv), Et3N (1.83 mL, 13.1 mmol,
3.00 equiv), DMAP (0.025 g), and CH2Cl2 (45 mL), in the order
given. The reaction mixture was cooled to 0 °C, and MsCl (0.678 mL,
114 mmol, 2.00 equiv) was added via syringe over 5 min. The solution
was allowed to stir at room temperature for 1 h and concentrated
under reduced pressure, and the crude material was filtered through a
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sparged through the reaction mixture for 10 min, and then the flask
was placed in an ice bath and cooled to ca. 2 °C. NaH dispersion
(0.193 g, 4.85 mmol, 1.00 equiv, 60%) was added, causing immediate
gas evolution and foaming, and giving a colorless solution. After 15
min, the ice bath was removed and the mixture was allowed to warm
to rt for 35 min. The reaction mixture was then poured into 5 M
NH4Cl (50 mL) and extracted with methyl t-butyl ether (2 × 50 mL).
The combined organic extracts were washed with H2O (1 × 100 mL)
and dried (MgSO4), and the solvents were removed in vacuo to give a
colorless solid that was recrystallized from EtOAc (3 mL) to give 1
(1.67 g, 3.98 mmol, 71%) as a colorless ca. 1:2 mixture of Esyn and Zsyn
conformers: mp 131 °C; 1H NMR (500 MHz, C6D6) δ 5.86 (br s, 0.3
H), 5.65−5.60 (m, 0.7 H), 4.07 (br s, 0.3 H), 3.59−3.50 (m, 1 H),
3.47−3.38 (m, 0.7 H), 2.22−2.12 (m, 2 H), 2.02−0.95 (m, 45 H),
0.6−0.15 (m, 2 H); 13C NMR (125 MHz, C6D6) δ 145.9 (s, 1JCP = 83
Hz), 143.1 (s, 1JCP = 24 Hz), 59.4 (d, 3JCP = 8 Hz), 57.6 (d, 3JCP = 12
DMAc (5 mL) and purified by trituration with cyclohexane to afford 5
(0.650 g, 1.58 mmol, 63%) as a colorless solid: mp 93 °C; H NMR
1
(500 MHz, CDCl3) δ 7.29−7.24 (m, 2 H), 7.00 (t, J = 7 Hz, 1 H),
6.81 (d, J = 7 Hz, 2 H), 5.69 (br s, 1 H), 3.01 (br s, 1 H), 2.20−2.10
(m, 2 H), 1.91−1.76 (m, 8 H), 1.78−1.38 (m, 11 H), 1.34−1.20 (m, 6
1
H), 1.09−0.95 (m, 3 H), 0.93−0.80 (m, 2 H), 0.46 (br q, JHB = 67
3
Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ 150.6 (s, JCP = 14 Hz),
1
146.7 (s, JCP = 70 Hz), 128.6 (d), 122.1 (d), 120.3 (d), 51.7 (d),
33.24 (d), 32.1 (d, 1JCP = 34 Hz), 26.9, 26.73, 26.70, 26.64, 26.61, 26.5,
26.02, 26.01, 25.3, 24.3; 31P NMR (202 MHz, CDCl3) δ 39.2; HRMS
m/z calcd for C25H43BN2P [M + H]+ 413.3251, found 413.3231. A
single crystal suitable for X-ray analysis was grown from cyclohexane.
The X-ray crystal structure data for this compound have been
deposited (CCDC No. 997592).
(N-Cyclohexyl,N′-phenylcarbamimidoyl)-di-tert-butylphosphine
Borane (6). Prepared according to General Procedure D from S6
(0.380 g, 1.89 mmol), di-t-butyl phosphine borane (0.363 g, 2.27
mmol, 1.20 equiv), and NaH (0.091 g, 3.00 mmol, 1.59 equiv, 60%) in
DMAc (5 mL) and purified by chromatography on SiO2 (hexanes) to
afford 6 (0.432 g, 1.20 mmol, 58%) as a yellow oil that crystallized on
standing: mp 99 °C; 1H NMR (500 MHz, CDCl3) δ 7.22 (t, J = 8 Hz,
2 H), 6.94 (t, J = 7 Hz, 1 H), 6.80 (d, J = 7.5 Hz, 2 H), 6.04 (br s, 1
H), 2.89−2.80 (m, 1 H), 1.65−1.25 (m, 22 H), 1.10−0.95 (m, 3 H),
3
3
Hz), 54.5 (d, JCP = 7 Hz), 50.3 (d, JCP = 6 Hz), 36.4 (t), 36.0 (d),
35.7 (d), 35.7 (t), 35.2 (t), 33.2 (d), 32.9 (d), 32.6, 29.2, 28.8, 27.6,
27.55, 27.53, 27.52, 27.49, 27.46, 27.44, 27.4, 27.02, 27.00, 26.87,
26.86, 26.8, 26.7, 26.6, 26.32, 26.31, 26.0, 25.4, 25.1; 31P NMR (202
MHz, C6D6) δ 50.9; HRMS m/z calcd for C25H49BN2P [M + H]+
419.3721, found 419.3707.
(N,N′-Dicyclohexylcarbamimidoyl)-di-tert-butylphosphine Bor-
ane (2). Prepared according to General Procedure D from DCC
(1.00 g, 4.84 mmol), di-t-butyl phosphine borane (0.931 g, 5.82 mmol,
1.20 equiv), and NaH (0.233 g, 5.82 mmol, 1.20 equiv, 60%) in DMAc
1
0.90−0.75 (m, 3 H), 0.58 (br q, JHB = 80 Hz, 3 H); 13C NMR (125
MHz, CDCl3) δ 150.5 (s, 3JCP = 13 Hz), 147.3 (s, 1JCP = 77 Hz), 128.5
4
3
(d), 121.7 (d), 119.8 (d, JCP = 1 Hz), 52.0 (d, JCP = 6 Hz), 33.8 (d,
1JCP = 26 Hz), 33.3, 31.6, 30.9, 28.9 (JCP = 2 Hz), 28.3 (q, JCP = 2
2
1
(12 mL) to afford 2 (1.02 g, 2.77 mmol, 58%) as a yellow oil: H
Hz), 28.2 (JCP = 2 Hz), 26.9, 25.3, 24.3, 22.7, 14.1; 31P NMR (202
MHz, CDCl3) δ 51.4 (1JPB = 40 Hz); HRMS m/z calcd for
C21H39BN2P [M + H]+ 361.2938, found 361.2920.
NMR (500 MHz, CDCl3) δ 5.65−5.60 (m, 1 H), 3.53−3.47 (m, 1 H),
3.39−3.30 (m, 1 H), 1.93−1.85 (m, 2 H), 1.80−1.70 (m, 6 H), 1.65−
1.50 (m, 3 H), 1.40−1.20 (m, 27 H), 0.90−0.20 (m, 3 H); 13C NMR
(125 MHz, CDCl3) δ 145.4 (s, 1JCP = 83 Hz), 57.6 (d, 3JCP = 12 Hz),
54.0 (d, 3JCP = 8 Hz), 34.9 (t), 34.6 (t), 33.5 (s, 1JCP = 27 Hz), 28.3 (q,
2JCP = 2 Hz), 26.9 (t), 26.0 (t), 25.5 (t), 24.8 (t), 24.6 (t); 31P NMR
(N-Cyclohexyl,N′-(3,5-trifluoromethyl)phenylcarbamimidoyl)-
dicyclohexylphosphine Borane (7). Prepared according to General
Procedure D from S7 (0.106 g, 0.315 mmol), dicyclohexyl phosphine
borane (0.080 g, 0.38 mmol, 1.20 equiv), and NaH (0.015 g, 0.38
mmol, 1.21 equiv, 60%) in DMAc (1.5 mL) and purified by
chromatography on SiO2 (5% EtOAc/hexanes) to afford 7 (0.095 g,
0.17 mmol, 55%) as a clear oil that solidified to a colorless solid on
standing: mp 97.5−98.9 °C; 1H NMR (400 MHz, CDCl3) δ 6.43 (t, 1
H, J = 9.2 Hz), 6.30 (d, 2 H, J = 6.8 Hz), 5.84 (br s, 1 H), 3.07 (br s, 1
H), 2.10−2.00 (m, 2 H), 1.90−0.75 (m, 36 H); 13C NMR (100 MHz,
CDCl3, CF3 not resolved) δ 164.5, 164.3, 162.0, 161.9, 153.2, 147.9 (d,
(202 MHz, CDCl3) δ 49.6; HRMS m/z calcd for C21H45BN2P [M +
H]+ 367.3408, found 367.3411.
(N,N′-Diphenylcarbamimidoyl)-di-tert-butylphosphine Borane
(3). Prepared according to General Procedure D from S5 (0.380 g,
1.96 mmol), di-t-butyl phosphine borane (0.376 g, 2.35 mmol, 1.20
equiv), and NaH (0.094 g, 2.4 mmol, 1.2 equiv, 60%) in DMAc (5
mL) and purified by recrystallization from cyclohexane to afford 3
1
(0.530 g, 1.49 mmol, 77%) as a colorless solid: mp 94 °C; H NMR
3
3
1JCP = 68 Hz), 103.5 (d, JCP = 25 Hz), 97.2 (t, JCP = 27 Hz), 52.0,
(500 MHz, CDCl3) δ 8.00 (br s, 1 H), 6.95 (q, J = 8 Hz, 4 H), 6.84 (t,
J = 7 Hz, 1 H), 6.74 (t, J = 7 Hz, 1 H), 6.64−6.61 (m, 4 H), 1.56 (s, 9
33.1, 32.3, 31.9, 26.9, 26.7, 26.7, 25.9, 25.2, 24.2; 31P NMR (162 MHz,
CDCl3) δ 41.1; 11B NMR (128 MHz, CDCl3) δ −44; HRMS m/z
calcd for C27H38F6N2P [M + H − BH3]+ 535.2677, found 535.2661.
(N-Phenyl,N′-4-methoxyphenylcarbamimidoyl)-dicyclohexyl-
phosphine Borane (8). Prepared according to General Procedure D
from S8 (0.200 g, 0.892 mmol), dicyclohexyl phosphine borane (0.227
g, 1.07 mmol, 1.20 equiv), and NaH (0.043 g, 1.1 mmol, 1.20 equiv,
60%) in DMAc (2 mL) and purified by chromatography on SiO2 (5%
EtOAc/hexanes) to afford 8 (0.275 g, 0.630 mmol, 71%) as an oily ca.
1:2 mixture of Esyn and Zsyn conformers: 1H NMR (400 MHz, CDCl3)
δ 7.65−7.48 (m, 1 H), 7.00−6.50 (m, 9 H), 3.67 (s, 3 H), 2.30−2.10
(m, 2 H), 1.95−1.20 (m, 20 H), 0.90−0.20 (m, 3 H); 13C NMR (100
MHz, CDCl3) 156.5 (s), 155.5 (s), 148.5 (s, JCP = 9 Hz), 145.2 (s, 1JCP
= 70 Hz), 144.6 (s, 1JCP = 38 Hz), 141.7 (JCP = 11 Hz), 131.3 (JCP = 6
Hz), 128.1, 123.9, 123.8, 122.3, 121.6, 120.5, 113.6, 113.4, 55.6 (q),
55.5 (q), 34.7, 34.5, 32.6, 32.2, 31.6, 29.1, 27.0, 26.8, 26.7, 26.62, 26.58,
26.0, 25.3, 22.7, 20.7, 14.1, 11.5; 31P NMR (162 MHz, CDCl3) δ 38.5;
11B NMR (128 MHz, CDCl3) δ −43; HRMS m/z calcd for
1
H), 1.54 (s, 9 H), 0.76 (br q, JHB = 85 Hz, 3 H); 13C NMR (125
MHz, CDCl3) δ 148.0 (s, 3JCP = 12 Hz), 146.1 (s, 1JCP = 76 Hz), 137.7
3
(s, JCP = 8 Hz), 128.00 (d), 127.96 (d), 123.9 (d), 122.4 (d), 121.9
(d), 120.3 (d), 34.2 (s, 1JCP = 26 Hz), 28.4 (q, 2JCP = 2 Hz); 31P NMR
(202 MHz, CDCl3) δ 52.0; HRMS m/z calcd for C21H33BN2P [M +
H]+ 355.2469, found 355.2465.
(N,N′-Diphenylcarbamimidoyl)-dicyclohexylphosphine Borane
(4). Prepared according to General Procedure D from S5 (0.300 g,
1.60 mmol), dicyclohexyl phosphine borane (0.395 g, 1.90 mmol, 1.19
equiv), and NaH (0.124 g, 1.90 mmol, 1.19 equiv, 60%) in DMAc
(3.86 mL) and purified by recrystallization from hexanes to afford 4
(0.45 g, 1.1 mmol, 69%) as a colorless solid: mp 99 °C; 1H NMR (500
MHz, CDCl3) δ 7.63 (s, 1 H), 7.10−6.70 (m, 8 H), 6.62 (d, J = 7.5
Hz, 2 H), 2.25−2.10 (m, 2 H), 1.95−1.60 (12 H), 1.55−1.40 (m, 3
1
H), 1.40−1.20 (m, 5 H), 0.60 (br q, JHB = 85 Hz, 3 H); 13C NMR
(125 MHz, CDCl3) δ 148.4 (d, 3JCP = 10 Hz), 145.1 (d, 1JCP = 67 Hz),
138.1 (s), 128.2 (d, JCP = 6 Hz), 124.0 (s), 122.6 (d), 121.6 (d), 120.4
1
1
C26H36N2OP [M + H − BH3]+ 423.2565, found 423.2534.
(d), 34.5 (d, JCP = 38 Hz), 32.4 (d, JCP = 31 Hz), 27.0, 26.8, 26.62,
26.58, 26.53, 26.46, 26.40, 26.36, 26.32, 25.88, 25.87, 25.65, 25.64,
24.76, 24.73; 31P NMR (202 MHz, CDCl3) δ 40.7. A single crystal
suitable for X-ray analysis was grown from cyclohexane. The X-ray
crystal structure data for this compound have been deposited (CCDC
No. 997591).
(N,N′-(R)-(+)-Methylbenzylcarbamimidoyl)-dicyclohexyl-
phosphine Borane (9). Prepared according to General Procedure D
from S9 (0.500 g, 2.00 mmol), dicyclohexyl phosphine borane (0.445
g, 2.10 mmol, 1.05 equiv), and NaH (0.084 g, 2.1 mmol, 1.1 equiv,
60%) in DMAc (5 mL) and purified by chromatography on SiO2 (5%
EtOAc/hexanes) to afford 9 (0.587 g, 1.27 mmol, 63%) as an an oily
ca. 1:1 mixture of Esyn and Zsyn conformers that partially crystallized on
standing: [α]D +53.2 (c 0.172, CH2Cl2); 1H NMR (500 MHz, CDCl3)
δ 7.40−7.19 (m, 8 H), 7.05−7.00 (m, 1.5 H), 6.79−6.75 (m, 1 H),
(N-Cyclohexyl,N′-phenylcarbamimidoyl)-dicyclohexylphosphine
Borane (5). Prepared according to General Procedure D from S6
(0.500 g, 2.50 mmol), dicyclohexyl phosphine borane (0.637 g, 3.00
mmol, 1.20 equiv), and NaH (0.120 g, 3.00 mmol, 1.20 equiv, 60%) in
9882
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The Journal of Organic Chemistry
Note
6.07−6.02 (m, 0.5 H), 5.70−5.63 (m, 0.5 H), 5.04 (pent, J = 7 Hz, 0.5
H), 4.75−4.63 (m, 1.5 H), 2.32−0.86 (m, 22 H), 1.46 (d, J = 7 Hz, 1.5
H), 1.36 (d, J = 6 Hz, 1.5 H), 1.31 (d, J = 7 Hz, 1.5 H), 1.04 (d, J = 6
Hz, 1.5 H), 0.9−0.2 (m, 3 H); 13C NMR (125 MHz, CDCl3) δ 147.5
(s, JCP = 1 Hz), 146.8 (s, JCP = 1 Hz), 145.8 (s, 1JCP = 84 Hz), 145.4 (s,
1JCP = 90 Hz), 143.3 (s), 143.1 (s), 128.7 (d), 128.3 (d), 128.2 (d),
127.9 (d), 127.1 (d), 126.44 (d), 126.39 (d), 126.2 (d), 126.0 (d),
(N-Cyclohexyl,N′-phenylcarbamimidoyl)-di(3,5-dimethyl-4-
methoxy)phenylphosphine Borane (13). Prepared according to
General Procedure D from S6 (0.070 g, 0.35 mmol), bis-3,5-
dimethyl-4-methoxyphenyl phosphine borane (0.132 g, 0.42 mmol,
1.2 equiv), and NaH (0.010 g, 0.42 mmol, 1.2 equiv, 60%) in
dimethylacetamide (5 mL) and purified by chromatography on SiO2
(10% EtOAc/hexanes) to afford 13 (0.153 g, 0.295 mmol, 85%) as a
1
3
3
clear oil: H NMR (300 MHz, CDCl3) δ 7.37−7.27 (m, 4 H), 7.05−
125.9 (d), 125.5 (d), 125.3 (d), 58.5 (d, JCP = 7 Hz), 57.1 (d, JCP
=
12 Hz), 54.8 (d, 3JCP = 8 Hz), 51.8 (d, 3JCP = 6 Hz), 34.9 (d, 1JCP = 28
Hz), 34.5 (d, 1JCP = 29 Hz), 32.5 (d, 1JCP = 23 Hz), 32.2 (d, 1JCP = 28
Hz), 28.7 (t), 28.1 (t), 28.0 (t), 27.8 (q), 27.4 (t), 26.89 (t), 26.85 (t),
26.80 (t), 26.78 (t), 26.75 (t), 26.71 (t), 26.69 (t), 26.66 (t), 26.61 (t),
26.6 (t), 26.5 (t), 26.32 (t), 26.31 (t), 26.20 (t), 26.18 (t), 26.14 (t),
26.10 (t), 26.02 (q), 25.97 (t), 25.95 (t), 25.67 (t), 25.65 (t), 25.4 (t),
25.3 (t), 25.25 (t), 25.24 (t), 23.0 (q); 31P NMR (202 MHz, CDCl3) δ
37.9, 36.9; HRMS m/z calcd for C29H45BN2P [M + H]+ 463.3408,
found 463.3441.
6.93 (br s, 2 H), 6.82−6.73 (t, 1 H, J = 7.2 Hz), 6.56 (br d, 2 H, J = 7.2
Hz), 5.62−5.50 (m, 1 H), 3.74 (s, 6 H), 3.6−3.4 (br, 1 H), 2.29 (s, 3
H), 2.25 (s, 9 H), 1.90−1.80 (m, 2 H), 1.60−0.85 (m, 11 H); 13C
NMR (100 MHz, CDCl3) δ 160.1 (JCP = 3 Hz), 159.9 (JCP = 3 Hz),
158.3, 134.9, 134.7, 134.0, 133.8, 133.6, 133.5, 132.3, 132.2, 131.6,
131.5, 131.44, 131.37, 128.1, 122.0, 121.1, 59.8, 32.7, 25.7, 24.4, 16.3;
31P NMR (162 MHz, CDCl3) δ 20.9; 11B NMR (128 MHz, CDCl3) δ
−37; HRMS m/z calcd for C31H40N2O2P [M + H − BH3]+ 503.2827,
found 503.2817.
(N-Cyclohexyl,N′-phenylcarbamimidoyl)-di-p-tolylphosphine
Borane (14). Prepared according to General Procedure D from S6
(0.160 g, 0.799 mmol), di-tolyl phosphine borane (0.219 g, 0.960
mmol, 1.20 equiv), and NaH (0.038 g, 0.96 mmol, 1.2 equiv, 60%) in
DMAc (5 mL) and purified by chromatography on SiO2 (2% EtOAc/
(N,N′-(R)-(−)-1-Cyclohexylethylcarbamimidoyl)-dicyclohexyl-
phosphine Borane (10). Prepared according to General Procedure D
from S10 (0.800 g, 3.04 mmol), dicyclohexyl phosphine borane (0.776
g, 3.66 mmol, 1.20 equiv), and NaH (0.146 g, 3.66 mmol, 1.20 equiv,
60%) in dimethylacetamide (7 mL) and purified by chromatography
on SiO2 (hexanes) to afford 10 (1.33 g, 2.80 mmol, 92%) as a yellow
oily ca. 1:1 mixture of Esyn and Zsyn conformers that formed a
crystalline solid on standing: [α]D −59.6 (c 0.225, CH2Cl2); mp 82
1
hexanes) to afford 14 (0.175 g, 0.410 mmol, 51%) as a clear oil: H
NMR (400 MHz, CDCl3) δ 7.73−7.50 (br s, 4 H), 7.20 (d, J = 6.8 Hz,
4 H), 7.10−6.96 (br s, 2 H), 6.88−6.80 (br s, 1 H), 6.70−6.51 (br s, 2
H), 5.65−5.48 (br s, 1 H), 3.6−3.1 (br, 1 H), 2.38 (s, 6 H), 1.76−0.80
(m, 13 H); 13C NMR (100 MHz, CDCl3) δ 155.9, 141.8 (4JCP = 2
Hz), 138.0, 131.0 (1JCP = 67 Hz), 131.0 (3JCP = 12 Hz), 129.6, 129.3
(3JCP = 12 Hz), 124.9, 122.7, 49.4, 33.6, 25.6, 24.9, 21.7; 31P NMR
(162 MHz, CDCl3) δ 20.9; 11B NMR (128 MHz, CDCl3) δ −38;
HRMS m/z calcd for C27H32N2P [M + H − BH3]+ 415.2303, found
415.2298.
(N,N′-(R)-(+)-Methylbenzylcarbamimidoyl)-di(3,5-methyl-4-
methoxy)phenylphosphine Borane (15). Prepared according to
General Procedure D from S9 (0.210 g, 0.840 mmol), di-3,5-
dimethyl-4-methoxyphenyl phosphine borane (0.279 g, 0.882 mmol,
1.20 equiv), and NaH (0.212 g, 0.882 mmol, 1.20 equiv, 60%) in
DMAc (3 mL) and purified by chromatography on SiO2 (15% EtOAc/
hexanes) to afford 15 (0.218 g, 0.384 mmol, 44%, adjusted for residual
solvent) as a clear oil: 1H NMR (400 MHz, CDCl3) δ 7.31−7.26 (m, 5
H), 7.14 (d, 2 H, J = 10.8 Hz), 7.09 (d, 2 H, J = 11.2 Hz), 6.96−6.86
(m, 3 H), 6.48 (d, J = 7.2 Hz, 2 H), 5.12 (p, J = 6.6 Hz, 1 H), 4.89 (d, J
= 4.0 Hz, 1 H), 4.62 (q, J = 6.2 Hz, 1 H), 3.70 (s, 3 H), 3.65 (s, 3 H),
2.16 (s, 6 H), 2.05 (s, 6 H), 1.4−0.9 (m, 3 H), 1.36 (d, J = 6.8 Hz, 3
H), 1.13 (d, J = 6.0 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 159.9
1
°C; H NMR (500 MHz, CDCl3) δ 5.20−5.13 (m, 1 H), 3.48−3.36
(m, 2 H), 2.17−1.50 (m, 28 H), 1.37−1.09 (m, 16 H), 1.06 (d, J = 6
Hz, 3 H), 1.01 (d, J = 6 Hz, 3H), 0.38 (br q, 1JHB = 78 Hz, 3 H); 13
C
NMR (125 MHz, CDCl3) δ 144.7 (s, 1JCP = 88 Hz), 57.4 (d, 3JCP = 13
Hz), 55.0 (d, 3JCP = 8 Hz), 45.5 (d), 43.9 (d), 32.4 (d, 1JCP = 35 Hz),
1
32.1 (d, JCP = 35 Hz), 30.2, 29.2, 29.0 (JCP = 4 Hz), 26.9, 26.8, 26.7,
26.6, 26.5, 26.4, 26.3, 26.2, 26.1, 25.9, 19.8 (q), 18.68 (q), 18.67 (q);
31P NMR (202 MHz, CDCl3) δ 37.4; HRMS m/z calcd for
C29H57BN2P [M + H]+ 475.4347, found 475.4324.
(N,N′-(R)-(+)-Methylbenzylcarbamimidoyl)-di-tert-butyl-
phosphine Borane (11). Prepared according to General Procedure D
from S9 (0.500 g, 2.00 mmol), di-tert-butyl phosphine borane (0.384
g, 2.40 mmol, 1.20 equiv), and NaH (0.096 g, 2.4 mmol) in DMAc
(5.0 mL) and purified by chromatography on SiO2 (5% EtOAc/
hexanes) to afford 11 (0.361 g, 0.880 mmol, 44%) as a clear oil: [α]D
+227 (c 0.120, CH2Cl2); 1H NMR (500 MHz, CDCl3) δ 7.38 (t, J = 8
Hz, 2 H), 7.34−7.26 (m, 7 H), 7.22 (tt, J = 1.5, 7 Hz, 1 H), 6.17 (br s,
1 H), 4.76 (q, J = 6 Hz, 1 H), 4.70 (pent, J = 7 Hz, 1 H), 1.45−1.25
(m, 21 H), 1.09 (d, J = 7 Hz, 3 H), 0.66 (br q, 1JHB = 79 Hz, 3 H); 13
NMR (125 MHz, CDCl3) δ 147.5 (s, JCP = 0.9 Hz), 147.0 (s, JCP
C
=
4
1
(4JCP = 3 Hz), 159.7 (4JCP = 3 Hz), 146.1 (1JCP = 92 Hz), 144.4 (1JCP
=
32 Hz), 133.8, 133.7, 133.2, 133.1, 132.2, 132.1 (3JCP = 12 Hz), 128.3,
127.3, 126.7, 126.0, 125.7, 125.4, 121.8, 121.3, 121.0, 120.4, 60.4, 59.7,
59.4, 59.3, 51.8, 51.7, 26.7, 23.0, 21.0, 16.1, 15.9, 14.2; 31P NMR (162
MHz, CDCl3) δ 13.0 (s); 11B NMR (128 MHz, CDCl3) δ −36;
HRMS m/z calcd for C35H42N2O2P [M + H − BH3]+ 553.2984, found
553.2980.
80 Hz), 145.1 (s), 128.7 (d), 128.4 (d), 127.2 (d), 126.4 (d), 126.1
3
3
(d), 125.5 (d), 58.3 (d, JCP = 12 Hz), 55.1 (d, JCP = 8 Hz), 34.0 (s,
1
2
1JCP = 18 Hz), 33.8 (s, JCP = 19 Hz), 28.5 (q, JCP = 2 Hz), 28.4 (q,
2JCP = 2 Hz), 26.9 (C6H12), 26.7 (q), 26.0 (q); 31P NMR (202 MHz,
CDCl3) δ 51.9; HRMS m/z calcd for C25H40BN2P [M + H]+
411.3095, found 411.3119.
(RP,1R,2S,5R)-Menthyl)phenylphosphinite Borane (16).8 A ffour-
neck 3 L flask equipped with a graduated 1 L addition funnel, inert gas
valve, and septum with thermocouple was charged with menthol (176
g, 1.13 mol). The flask was then twice backfilled with Ar, and
anhydrous THF (1.00 L) was charged via canula under N2 pressure.
An endotherm to 6 °C was observed. The resulting colorless solution
was cooled to 2 °C in an ice bath, and n-BuLi (683 mL, 1.64 M, 1.12
mol, 0.99 equiv) was then charged to the addition funnel and added
dropwise to the cold menthol solution. It was necessary to stop the
addition several times and allow the internal temperature to fall again
to ∼6 °C before resuming the addition. The entire addition required
1.5 h, and the internal temperature rose to a maximum of 14 °C.
A separate four-neck 5 L flask equipped with a mechanical stirrer,
inert gas valve, and septa with a thermocouple was charged with
PhPCl2 (152.0 mL, 1.120 mol, 1.000 equiv). The flask was then
evacuated and backfilled with Ar, and MTBE (0.500 L) was charged
via cannula under N2 pressure. The resulting solution was cooled to
−78 °C under Ar. The cold (∼3 °C) menthoxide solution from above
(N,N′-(R)-(−)-1-Cyclohexylethylcarbamimidoyl)-di-tert-butyl-
phosphine Borane (12). Prepared according to General Procedure D
from S10 (1.00 g, 3.81 mmol), di-tert-butyl phosphine borane (0.731
g, 4.57 mmol, 1.20 equiv), and NaH (0.146 g, 4.57 mmol, 1.20 equiv,
60%) in DMAc (10 mL) and purified by chromatography on SiO2
(hexanes) to afford 12 (0.571 g, 1.35 mmol, 35%) as a yellow oil that
formed a crystalline solid on standing: mp 84 °C; [α]D −66.3 (c 0.310,
1
CH2Cl2); H NMR (500 MHz, CDCl3) δ 5.73 (m, 1 H), 3.49−3.43
(m, 1 H), 3.41−3.34 (m, 1 H), 1.85 (t, J = 15 Hz, 2 H), 1.80−1.62 (m,
8 H), 1.40−1.00 (m, 30 H), 1.06 (d, J = 6.5 Hz, 3 H), 1.02 (d, J = 6.5
Hz, 3 H), 0.52 (br q, JHB = 69 Hz, 3 H); 13C NMR (125 MHz, CDCl3)
δ 146.2 (s, 1JCP = 83 Hz), 58.1 (d, 3JCP = 13 Hz), 55.2 (d, 3JCP = 8 Hz),
45.6 (d), 43.9 (d), 33.9 (s, 1JCP = 27 Hz), 33.3 (s, 1JCP = 27 Hz), 30.1
(t), 29.5 (t), 29.3 (t), 29.0 (t), 28.5 (q, 2JCP = 2 Hz), 28.3 (q, 2JCP = 2
4
Hz), 26.8 (t), 26.7 (t), 26.6 (t), 26.4 (t), 26.3 (t, JCP = 1 Hz), 19.8
(q), 17.9 (q, 4JCP = 1 Hz); 31P NMR (202 MHz, CDCl3) δ 49.6 (1JPB
=
46 Hz); HRMS m/z calcd for C25H53BN2P [M + H]+ 423.4034, found
423.4023.
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Note
was transferred via cannula under N2 pressure to the MTBE solution
over 1.5 h while maintaining an internal temperature below −50 °C.
The cold bath was removed, and the reaction mixture was stirred at
room temperature for 1.5 h, giving a nearly colorless fine slurry. This
mixture was cooled again to −78 °C, and 95% LiBH4 (29.3 g, 1.34
mol, 1.2 equiv, weighed in a glovebox) was added at once by quickly
removing a septum while flowing an external source of N2 through the
flask. An exotherm to −45 °C was observed. The external N2 source
was removed, and the reaction mixture was warmed to room
temperature overnight.
equiv) in THF (6 mL) and purified by chromatography on SiO2 (15%
EtOAc/hexanes) to afford 18 (0.024 g, 0.050 mmol, 20% accounting
for solvent impurity) as a sticky clear oil: [α]D −9.8 (c 0.8, CH2Cl2);
1H NMR (500 MHz, CDCl3) δ 7.82−7.77 (m, 2 H), 7.52−7.42 (m, 3
H), 5.35 (br s, 1 H), 4.39−4.31 (m, 1 H), 3.90−3.71 (m, 1 H), 3.40−
3.32 (m, 1 H), 2.11−2.03 (m, 3 H), 1.80−0.60 (m, 38 H); 13C NMR
(125 MHz, CDCl3) δ 147.0, 134.2, 133.7, 131.9, 131.0, 130.8, 128.6,
128.5, 80.6 (2JCP = 6 Hz), 57.9 (JCP = 17 Hz), 49.1 (JCP = 6 Hz), 43.3,
34.5, 34.0, 33.9, 32.3, 32.2, 31.4, 26.1, 26.0, 25.6, 24.8, 24.6, 24.5, 22.7,
21.9, 21.1, 15.8; 31P NMR (202 MHz, CDCl3) δ 94.0; 11B NMR (160
MHz, CDCl3) δ −39.5; HRMS m/z calcd for C29H48N2OP [M + H −
BH3]+ 471.3504, found 471.3498.
A separate three-neck 5 L flask equipped with a mechanical stirrer
was charged with ice (500 g), H2O (500 mL), and conc. HCl (230
mL). The reaction mixture from above was slowly added in small
portions over 30 min. The resulting mixture was stirred for 15 min and
then poured into a 5 L separatory funnel, and the phases were
separated. The lower, aqueous layer was then extracted with MTBE (2
× 1 L). The solvents from the combined organic extracts were
removed under reduced pressure, giving a viscous, nearly colorless oil.
This oil was then washed through a wide column of 750 g of SiO2 that
had been prewetted with hexanes:MTBE (1:1). The product
containing fractions were combined, and the solvents were removed
in vacuo to give a viscous oil (175 g). A seed crystal of the product
phosphinite borane was added, causing a slow crystallization of the
batch, which, upon filtration, afforded 16 (88.0 g, 28% overall yield) as
a colorless, crystalline solid 52:48 RP:SP mixture of diastereomers. A
portion of this solid (20.0 g) was recrystallized twice (hexanes),
ultimately affording 16 (3.50 g, 12.6 mmol, ca. 5% overall yield, >15:1
RP:SP) as colorless needles: mp 96 °C; [α]D −113.1 (c 1.0, CH2Cl2);
1H NMR (500 MHz, CDCl3) δ 7.81−7.76 (m, 2 H), 7.59−7.56 (m, 1
H), 7.53−7.48 (m, 2 H), 7.16 (dq, 1JHP = 396 Hz, 2JHB = 5.7 Hz, 1 H),
3.89 (dq, 1 H, J = 10 Hz, 4 Hz), 2.07−2.01 (m, 2 H), 1.65−1.49 (m, 2
H), 1.41−1.35 (m, 2 H), 1.24−0.68 (m, 6 H), 0.88 (d, J = 6 Hz, 6 H),
0.63 (d, J = 7 Hz, 3 H); 13C NMR (125 MHz, CDCl3) δ 132.6 (d, 2JCP
General Procedure F: Deprotection of Phosphine Boranes to
Afford Phosphine Oxides. (N-Cyclohexyl,N′-phenylcarbam-
imidoyl)-di(3,5-dimethyl-4-methoxy)phenylphosphine (19). A sol-
ution of 13 (0.095 g, 0.18 mmol) in toluene (3 mL) was treated with
DABCO (0.404 g, 0.736 mmol, 4.00 equiv) and stirred at 65 °C for 1.5
h under N2. The reaction mixture was directly added on top of a SiO2
column and purified by chromatography on SiO2 (10% EtOAc/
hexanes) to afford 19 (0.067 g, 0.13 mmol, 72%) as a colorless sticky
1
oil: H NMR (400 MHz, CDCl3) δ 7.06−7.01 (m, 6 H), 6.86 (t, J =
7.2 Hz, 1 H), 6.64 (d, J = 7.6 Hz, 1 H), 4.42 (d, J = 7.2 Hz, 1 H), 4.01
(br s, 1 H), 3.75 (s, 6 H), 2.27 (s, 12 H), 1.92 (br d, 2 H, J = 8.0 Hz),
1.52−1.11 (m, 9 H), 1.00−0.88 (m, 1 H); 13C NMR (100 MHz,
CDCl3) δ 158.3, 157.9 (1JCP = 37 Hz), 151.3 (3JCP = 12 Hz), 134.8
(2JCP = 21 Hz), 131.4 (3JCP = 8 Hz), 129.1, 129.0, 128.0, 123.1, 121.8,
59.8, 49.0, 32.3, 25.9, 24.1, 16.2; 31P NMR (162 MHz, CDCl3) δ
−15.5; HRMS m/z calcd for C31H40N2O2P [M + H]+ 503.2827, found
503.2826.
(N-Cyclohexyl,N′-phenylcarbamimidoyl)-di-p-tolylphosphine
(20). Prepared according to General Procedure F from 14 (0.122 g,
0.285 mmol) and DABCO (0.132 g, 1.14 mmol, 4.00 equiv) in toluene
(5 mL) and purified by chromatography on SiO2 (10% EtOAc/
1
1
hexanes) to afford 20 (0.094 g, 0.23 mmol, 80%) as a yellow oil: H
= 2.3 Hz), 132.1 (d), 132.0 (d), 129.5 (s, JCP = 63 Hz), 128.9 (d),
2
3
NMR (400 MHz, CDCl3) δ 7.23 (t, J = 8.0 Hz, 4 H), 7.15 (d, J = 8.0
Hz, 4 H), 7.04 (d, J = 8.0 Hz, 2 H), 6.85 (br s, 1 H), 6.65 (br s, 2 H),
4.35−4.23 (br s, 1 H), 4.02−3.89 (br s, 1 H), 2.36 (s, 6 H), 2.00−1.90
(m, 2 H), 1.53−1.51 (m, 3 H), 1.38−1.36 (m, 2 H), 1.18−1.13 (m, 3
H); 13C NMR (100 MHz, CDCl3) δ 150.2 (1JCP = 46 Hz), 149.8 (1JCP
= 67 Hz), 142.4, 132.2 (3JCP = 9 Hz), 129.1 (3JCP = 13 Hz), 128.6,
128.3, 127.5, 122.0, 120.6, 51.6, 33.4, 25.3, 24.7, 21.6; 31P NMR (162
MHz, CDCl3) δ −16.2 (s); HRMS m/z calcd for C27H32N2P [M +
H]+ 415.2303, found 415.2298.
128.8 (d), 80.1 (d, JCP = 7 Hz), 48.8 (d, JCP = 5 Hz), 42.3 (t, JCP
=
1.5 Hz), 34.0 (t), 31.5 (d, JCP = 3 Hz), 25.6 (d), 23.0 (t), 22.0 (q), 20.9
(q), 15.8 (q); 31P NMR (202 MHz, CDCl3) δ 91.9 (1JPH = 389 Hz,
1JPB = 63 Hz).
General Procedure E: Preparation of Phosphinite Boranes.
(1R,2S,5R-Menthyl)(N,N′-(R)-(+)-methylbenzylcarbamimidoyl)-
phenylphosphinite Borane (17). A 15 mL three-neck, round-bottom
flask equipped with a direct Ar line, inert gas valve, and septum with
thermocouple was charged with 16 (0.300 g 1.05 mmol, 1 equiv), S9
(0.319 g, 1.26 mmol, 1.2 equiv), and dry THF (3.0 mL). The solution
was sparged with Ar for 15 min and cooled to −78 °C, and n-BuLi
(0.66 mL, 1.05 mmol, 1 equiv, 1.6 M in hexane) was added dropwise
via syringe, giving a yellow reaction mixture. The cold bath was
removed, and the mixture was allowed to warm to rt for 30 min. The
reaction mixture was applied directly to a silica gel cartridge (40 g) and
purified by chromatography on SiO2 (20:1, hexanes:EtOAc) to afford
17 (0.290 g, 0.549 mmol, 52%) as a clear, colorless oil: [α]D −2.5 (c
0.028, CH2Cl2); 1H NMR (500 MHz, CDCl3) δ 7.63−7.60 (m, 2 H),
7.39−7.24 (m, 10 H), 6.94−6.86 (m, 3 H), 6.55 (d, J = 7 Hz, 2 H),
5.87 (d, J = 5 Hz, 1 H), 5.14 (pent, J = 7 Hz, 1 H), 4.70 (q, J = 6 Hz, 1
H), 4.35−4.25 (m, 1 H), 1.79−1.72 (m, 2 H), 1.59−1.54 (m, 4 H),
1.56 (d, J = 7 Hz, 3 H), 1.27−0.61 (m, 3 H), 0.98 (d, J = 6 Hz, 3 H),
0.95−0.85 (m, 3 H), 0.77 (t, J = 6 Hz, 6 H), 0.58 (d, J = 7 Hz, 3 H);
13C NMR (125 MHz, CDCl3) δ 146.9 (s, 1JCP = 46 Hz), 146.6 (s, 4JCP
(N,N′-Dicyclohexylcarbamimidoylium)-dicyclohexylphosphine
Borane Tetrafluoroborate (21). A solution of phosphine borane 1
(0.077 g, 0.18 mmol) in CH2Cl2 (1.5 mL) was cooled to 0 °C under
Ar and treated with HBF4 diethyl ether complex (0.37 mL, 2.8 mmol,
15 equiv). After 30 min at 0 °C, the reaction mixture was warmed to rt
over 30 min. The solution was then left open to air, treated with an
equal volume of HBF4 (conc. aq.), and stirred for 30 min more. The
solution was then diluted with water (5 mL) and extracted with
CH2Cl2 (2 × 15 mL). The combined organic extracts were washed
with brine, dried (Na2SO4), and concentrated to afford 21 (0.075 g,
0.15 mmol, 81%) as a colorless crystalline solid: mp 259−261 °C; 1H
NMR (400 MHz, CDCl3) δ 7.46−7.34 (br s, 1 H), 4.75−4.65 (m, 1
H), 3.62−3.38 (m, 2 H), 2.40−2.25 (m, 2 H), 1.95−1.10 (m, 38 H),
0.9−0.1 (m, 3 H); 13C NMR (100 MHz, CDCl3,) δ 158.1 (1JCP = 30
Hz), 156.2 (1JCP = 27 Hz), 58.6, 53.3 (3JCP = 3 Hz), 34.9, 34.7, 32.8,
32.6, 32.1, 31.8, 31.2, 28.3, 27.8, 27.7, 27.2, 26.42, 26.38, 26.3, 26.0,
25.9, 25.8, 25.7, 25.42, 25.40, 25.1, 25.0, 24.4, 24.2, 23.2; 31P NMR
(162 MHz, CDCl3) δ 60.0, 56.9; 11B NMR (128 MHz, CDCl3,
measured without lock) δ −0.9, −45.4. These spectra exhibit a mixture
of Esyn + Zsyn conformers. A single crystal suitable for X-ray analysis
was grown from hexanes/acetone (1:1). The X-ray crystal structure
data for the compound has been deposited, with CCDC No. 997593.
N-Cyclohexyl,N′-phenylcarbamimidoyl)-di(3,5-dimethyl-4-
methoxyphenyl)phosphine Oxide (22). A solution of phosphine 19
(0.052 g, 0.10 mmol) in acetone (1 mL) was treated with hydrogen
peroxide (0.12 mL, 0.11 mmol, 3% aq. solution). The reaction mixture
was stirred for 1 h at rt; TLC analysis (10% EtOAc/hexanes) showed a
= 0.8 Hz), 145.2 (s), 143.7 (s), 132.6 (s, 1JCP = 58 Hz), 131.8 (s, 4JCP
=
3 Hz), 130.6 (d), 130.5 (d), 128.63 (d), 128.54 (d), 128.4 (d), 127.3
(d), 126.7 (d), 126.3 (d), 126.0 (d), 125.7 (d), 125.4 (d), 81.2 (d, 2JCP
= 5 Hz), 57.6 (d, 3JCP = 14 Hz), 51.2 (d, JCP = 5 Hz), 48.7 (d, 3JCP = 58
Hz), 43.4 (t, JCP = 0.5 Hz), 33.9 (t), 31.4 (d), 26.9 (t, C6H12), 26.2
(q), 25.8 (d), 24.6 (q), 22.60 (d), 22.57 (t), 22.0 (q), 20.8 (q), 15.6
(q); 31P NMR (202 MHz, CDCl3) δ 96.1; HRMS m/z calcd for
C33H47BN2OP [M + H]+ 529.3514, found 529.3535.
(1R,2S,5R-Menthyl)(N,N′-dicyclohexylcarbamimidoyl)phenyl-
phosphinite Borane (18). Prepared according to General Procedure E
from 16 (0.080 g, 0.29 mmol, 1.2 equiv), DCC (0.050 g, 0.24 mmol,
1.0 equiv), and n-BuLi (0.18 mL, 0.29 mmol, 1.6 M in hexane, 1.2
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The Journal of Organic Chemistry
Note
clean and quantitative oxidation. The solution was extracted with Et2O
(2 × 10 mL). The combined organic extracts were washed with water
(10 mL) and brine (10 mL), dried (Na2SO4), and concentrated to
afford phosphine oxide 22 (0.053 g, 0.10 mmol, 99%) as a sticky
(5 mL) was sparged with Ar for 10 min and then cooled to 0 °C and
treated with NaH (0.022 g, 0.54 mmol, 60% dispersion). The reaction
mixture turned yellow and was stirred for 20 min at 0 °C, warmed to rt
for 20 min, exposed to air, quenched with sat. aq. NH4Cl solution, and
extracted with diethyl ether (3 × 30 mL). The combined organic
extracts were washed with H2O (50 mL) and brine (50 mL), dried
(Na2SO4), and concentrated to give a crude residue that was purified
by chromatography on SiO2 (10% EtOAc/hexanes) to afford
phosphine borane 25 (0.319 g, 0.712 mmol, 78%) as a colorless
crystalline solid: mp 189.7−191.5 °C; 1H NMR (400 MHz, CDCl3) δ
8.01 (d, 1 H, J = 8.0 Hz), 7.98 (d, 1 H, J = 8.4 Hz), 7.85 (d, 1 H, J =
8.0 Hz), 7.82 (d, 1 H, J = 8.4 Hz), 7.42 (s, 1 H), 7.31 (td, 4 H, J = 6.4,
2.0 Hz), 6.86−6.80 (m, 3 H), 6.79−6.72 (m, 2 H), 6.63−6.54 (m, 2
H), 6.42 (d, 1 H, J = 7.6 Hz), 3.23−3.15 (m, 1 H), 2.97−2.86 (m, 1
H), 2.78−2.66 (m, 2 H), 2.43 (s, 3 H), 2.41 (s, 3 H); 13C NMR (100
MHz, CDCl3) δ 148.7 (1JCP = 91 Hz), 148.0 (3JCP = 13 Hz), 142.7
(4JCP = 2 Hz), 142.1 (4JCP = 2 Hz), 137.3 (3JCP = 10 Hz), 136.9, 133.6
(2JCP = 10 Hz), 133.2 (2JCP = 10 Hz), 130.7, 130.4, 129.6 (3JCP = 11
Hz), 128.4, 126.6, 126.5, 125.4, 124.2 (1JCP = 64 Hz), 123.3 (1JCP = 61
Hz), 122.6, 119.6, 31.1, 29.2, 21.7, 21.6; 31P NMR (162 MHz, CDCl3)
δ 19.4; 11B NMR (128 MHz, CDCl3) δ −40.4; IR (ATR) 3340, 3026,
2378, 1637, 1486, 1356, 1128, 1045, 908, 802, 734 cm-1; HRMS m/z
calcd for C29H28N2P [M + H − BH3]+ 435.1990, found 435.1975.
6-(Di-(3,5-dimethyl-4-methoxy)phenylphosphanyl)-12,13-dihy-
dro-5H-dibenzo[d,h][1,3]diazonine Borane (26). A solution of
carbodiimide 23 (0.084 g, 0.38 mmol) and di-(3,5-dimethyl-4-
methoxy)phosphine borane (0.133 g, 0.545 mmol) in DMAc (3
mL) was sparged with Ar for 10 min, cooled to 0 °C, and treated with
NaH (0.018 g, 0.458 mmol, 60% dispersion). The reaction mixture
turned yellow and was stirred for 20 min at 0 °C, warmed to rt for 20
min, exposed to air for 30 min, quenched with sat. aq. NH4Cl (3 mL),
and extracted with diethyl ether (3 × 30 mL). The combined organic
extracts were washed with H2O (50 mL) and brine (50 mL), dried
(Na2SO4), and concentrated to give a crude residue that was purified
by chromatography on SiO2 (10% EtOAc/hexanes) to afford
phosphine borane 26 (0.176 g, 0.328 mmol, 86%) as a colorless
foam: 1H NMR (400 MHz, CDCl3) δ 7.79 (d, 2 H, J = 10.8 Hz), 7.54
(d, 2 H, J = 11.2 Hz), 7.43 (s, 1 H), 6.89−6.83 (m, 3 H), 6.80−6.74
(m, 2 H), 6.63−6.55 (m, 2 H), 6.44 (d, 1 H, J = 7.6 Hz), 3.79 (s, 3 H),
3.76 (s, 3 H), 3.27−3.18 (m, 1 H), 2.92−2.81 (m, 1 H), 2.79−2.68
(m, 2 H), 2.36 (s, 6 H), 2.33 (s, 6 H); 13C NMR (125 MHz, CDCl3) δ
160.5 (4JCP = 2 Hz), 159.9 (4JCP = 2 Hz), 149.2 (1JCP = 91 Hz), 148.0
(3JCP = 13 Hz), 137.3 (3JCP = 10 Hz), 136.6, 134.3 (2JCP = 11 Hz),
133.8 (2JCP = 10 Hz), 131.8 (3JCP = 24 Hz), 131.8, 130.6 (3JCP = 17
Hz), 128.4, 126.7, 126.5, 126.4, 125.1, 122.6, 122.0 (1JCP = 65 Hz),
120.9 (1JCP = 60 Hz), 119.4, 59.8, 59.7, 31.2, 28.8, 16.4, 16.3; 31P NMR
(162 MHz, CDCl3) δ 19.8; 11B NMR (128 MHz, CDCl3) δ −38.3; IR
(ATR) 3345, 2934, 2378, 1637, 1480, 1278, 1114, 917, 734 cm−1;
HRMS m/z calcd for C33H36N2O2P [M + H − BH3]+ 523.2514, found
523.2494.
1
colorless gum: H NMR (400 MHz, CDCl3) δ 7.60−7.41 (m, 3 H),
7.22−6.60 (m, 5 H), 6.30−6.20 (br s, 1 H), 3.74 (s, 6 H), 2.28 (s, 12
H), 1.78−0.95 (m, 11 H); 13C NMR (100 MHz, CDCl3) δ 160.4 (s),
132.9, 132.8, 131.3, 131.2, 128.2, 126.3, 125.3, 122.0, 120.8, 59.6, 33.3,
25.4, 24.7, 16.2; 31P NMR (162 MHz, CDCl3) δ 20.0; HRMS m/z
calcd for C31H40N2O3P [M + H]+ 519.2777, found 519.2764.
5,6-Didehydro-12,13-dihydro-5H-dibenzo[d,h][1,3]diazonine
(23).13 A solution of dianiline (3.50 g, 16.4 mmol) in 2 M HCl (60
mL) was cooled to 0 °C and treated dropwise with a solution of
sodium nitrite (4.60 g, 66.8 mmol) in H2O (30 mL). The reaction
mixture turned yellow and was left to stir for 1 h at 0 °C and then was
treated dropwise with a solution of sodium azide (4.45 g, 68.4 mmol)
in H2O (35 mL). The mixture was allowed to warm to rt for 14 h, and
a tan precipitate formed. After addition of CH2Cl2 (75 mL) and H2O
(10 mL), the organic layer was dried (Na2SO4) and concentrated in
vacuo to afford the bis-azide (2.86 g, 10.8 mmol, 66%) as a tan solid
that was used without further purification: 1H NMR (400 MHz,
CDCl3) δ 7.35- 7.04 (m, 8 H), 2.85 (s, 4 H); IR (ATR) 3085, 2993,
2115, 1485, 1286, 1163, 751 cm−1.
A solution of bis-azide (0.749 g, 2.83 mmol) in ether (10 mL) was
treated at rt with triphenylphosphine (1.49 g, 5.67 mmol). The opaque
reaction mixture was stirred at rt for 14 h and concentrated to afford
the bis-iminophosphorane (1.852 g, 2.52 mmol, 89%) as a brown solid
that was used without further purification: 1H NMR (400 MHz,
CDCl3) δ 7.85−7.23 (m, 32 H), 7.12−7.01 (d, 3 H, J = 6.6 Hz), 6.80−
6.45 (m, 6 H), 3.23−3.05 (s, 4 H); IR (ATR) 3026, 1594, 1479, 1450,
1340, 1103, 726, 691 cm−1.
A suspension of bis-iminophosphorane (7.55 g, 10.3 mmol) in
CH2Cl2 (300 mL) was treated at rt with Boc-anhydride (4.49 g, 20.6
mmol) and DMAP (1.26 g, 10.3 mmol). The reaction mixture was
allowed to stir for 12 h under N2 and became a transparent brown
solution. Evaporation of the solvent led to a dark residue that was
purified by chromatography on SiO2 (15% EtOAc/hexanes) to
provide a crude product that was recrystallized (hexanes) to afford
carbodiimide 23 (1.17 g, 2.27 mmol, 52%) as a brown flaky solid: mp
141.9−142.8 °C; 1H NMR (400 MHz, CDCl3) δ 7.37−7.20 (m, 4 H),
7.16−7.01 (m, 4 H), 3.41−3.27 (m, 2 H), 3.12−2.97 (m, 2 H); IR
(ATR) 2974, 2104, 2091, 1737, 1595, 1450, 1140, 734 cm−1. This
material contained ca. 10% of dimeric bis-carbodiimide that was readily
removed in subsequent tranformations.
6-(Di-tert-butylphosphanyl)-12,13-dihydro-5H-dibenzo[d,h][1,3]-
diazonine Borane (24). A solution of carbodiimide 23 (0.065 g, 0.30
mmol) and di-t-butyl phosphine borane (0.057 g, 0.35 mmol) in
DMAc (1.2 mL) was sparged with Ar for 10 min, cooled to 0 °C, and
treated with NaH (0.014 g, 0.35 mmol, 60% dispersion). The reaction
mixture was stirred for 10 min at 0 °C, warmed to rt over 20 min,
exposed to air, stirred for 30 min, and quenched with sat. aq. NH4Cl.
The mixture was extracted with diethyl ether (3 × 30 mL), and the
combined organic extracts were washed with H2O (50 mL) and brine
(50 mL), dried (Na2SO4), and concentrated to provide a crude residue
that was purified by chromatography on SiO2 (5% EtOAc/hexanes) to
afford 24 (0.075 g, 0.20 mmol, 67%) as a colorless crystalline solid: mp
174−177 °C; 1H NMR (400 MHz, CDCl3) δ 7.61 (s, 1 H), 6.92−6.73
(m, 5 H), 6.69 (d, 1 H, J = 7.2 Hz), 6.63 (t, 1 H, J = 7.2 Hz), 6.49 (d, 1
H, J = 7.6 Hz), 3.45−3.26 (m, 2 H), 2.97−2.83 (m, 2 H), 1.58 (s, 9
H), 1.54 (s, 9 H); 13C NMR (100 MHz, CDCl3) δ 147.9 (3JCP = 11
Hz), 146.3 (1JCP = 75 Hz), 137.7, 137.5 (3JCP = 8 Hz), 130.9, 130.2,
128.4, 127.0, 126.7, 126.6, 126.5, 122.3, 120.3, 34.3 (1JCP = 27 Hz),
33.6 (1JCP = 26 Hz), 30.4 (2JCP = 7 Hz), 28.8, 28.2; 31P NMR (162
MHz, CDCl3) δ 52.6; 11B NMR (128 MHz, CDCl3) δ −42; HRMS
m/z calcd for C23H34N2PB [M + H]+ 381.2631, found 381.2622. The
X-ray crystal structure data for this compound have been deposited
(CCDC No. 1008171).
6-(Cyclohexylphenylphosphanyl)-12,13-dihydro-5H-dibenzo-
[d,h][1,3]diazonine Borane (27). A solution of carbodiimide 23
(0.100 g, 0.454 mmol) and phenylcyclohexyl phosphine borane (0.112
g, 0.545 mmol) in DMAc (2 mL) was sparged with Ar for 10 min,
cooled to 0 °C, and treated with NaH (0.022 g, 0.55 mmol, 60%
dispersion). The reaction mixture turned yellow and was stirred for 20
min at 0 °C, warmed to rt for 20 min, exposed to air for 30 min,
quenched with sat. aq. NH4Cl (2 mL) solution, and extracted with
diethyl ether (3 × 30 mL). The combined organic extracts were
washed with H2O (50 mL) and brine (50 mL), dried (Na2SO4), and
concentrated to give a crude residue that was purified by
chromatography on SiO2 (hexanes) to afford phosphine borane 27
(0.134 g, 0.314 mmol, 69%) as a colorless solid that exists as an
equilibrating mixture of diastereomers in solution: mp 164−166 °C;
1H NMR (400 MHz, CDCl3) δ 8.18−8.09 (m, 2 H), 7.63−7.48 (m, 3
H), 7.28 (s, 0.7 H), 7.13 (s, 0.3 H), 6.93−6.74 (m, 4 H), 6.69 (d, 1 H,
J = 7.6 Hz), 6.65−6.54 (m, 2 H), 6.49 (d, 1 H, J = 7.6 Hz), 3.20−3.09
(m, 0.5 H), 3.10 (dd, 1 H, J = 9.6, 2.4 Hz), 3.04−2.71 (m, 1.5 H),
2.69−2.60 (m, 1 H), 2.58−2.43 (m, 1.5 Hz), 2.30−2.15 (m, 1 H),
1.97−1.86 (m, 1 H), 1.80−1.65 (m, 3 H), 1.48−1.17 (m, 6 H), 1.1−
6-(Di-tolylphosphanyl)-12,13-dihydro-5H-dibenzo[d,h][1,3]-
diazonine Borane (25). A solution of carbodiimide 23 (0.200 g, 0.907
mmol) and di-tolyl phosphine borane (0.249 g, 1.09 mmol) in DMAc
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The Journal of Organic Chemistry
Note
0.4 (br, 3 H); 13C NMR (100 MHz, CDCl3) δ 148.1, 148.0, 147.4
(1JCP = 57 Hz), 137.2, 137.1, 133.0, 132.9, 132.1, 130.7, 130.5, 130.4,
128.8, 128.7, 128.7, 128.6, 128.5, 127.1, 126.8, 126.5, 126.4, 126.3,
125.5, 124.9, 122.6, 119.9, 119.8, 33.5, 33.2, 33.1, 31.1, 30.7, 30.2, 28.4,
26.7, 26.5, 26.4, 25.9, 25.2; 31P NMR (162 MHz, CDCl3) δ 27.1, 25.3;
11B NMR (128 MHz, CDCl3) δ −44.3; IR (ATR) 3353, 2934, 2385,
31.0, 29.0, 16.3, 16.2; 31P NMR (162 MHz, CDCl3) 18.5; IR (ATR)
3202, 2934, 1627, 1480, 1286, 1215, 1163, 1115, 994, 758 cm−1;
HRMS m/z calcd for C33H36N2PO3 [M + H]+ 539.2464, found
539.2443.
ASSOCIATED CONTENT
* Supporting Information
■
1644, 1474, 1435, 1260, 726, 692 cm−1; HRMS m/z calcd for
C27H33N2PB [M + H]+ 427.2474, found 427.2466.
S
Spectral data for all new compounds as well as CIF files and
ORTEP plots for compounds 4, 5, 21, and 24. This material is
available free of charge via the Internet at http://pubs.acs.org.
6-(Di-tolylphosphanyl)-12,13-dihydro-5H-dibenzo[d,h][1,3]-
diazonine (28). A solution of phosphine borane 25 (0.071 g, 0.16
mmol) in toluene (2 mL) was treated under an Ar atmosphere with
DABCO (0.025 g, 0.22 mmol) and stirred at 60 °C for 90 min. After
cooling to rt, the reaction mixture was purified by chromatography on
SiO2 (5% EtOAc/hexanes) to afford phosphine 28 (0.056 g, 0.13
mmol, 81%) as sticky clear oil: 1H NMR (400 MHz, CDCl3) δ 7.72−
7.48 (m, 4 H), 7.25−7.19 (m, 2 H), 6.88−6.76 (m, 2 H), 6.76−6.59
(m, 3 H), 6.54 (d, 2 H, J = 7.6 Hz), 3.38 (d, 2 H, J = 8.8 Hz), 2.83 (d,
2 H, J = 9.2 Hz), 2.38 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ 156.5,
AUTHOR INFORMATION
Corresponding Authors
*E-mail: pwipf@pitt.edu (P.W.).
■
*E-mail: carl.busacca@boehringer-ingelheim.com (C.A.B.).
Notes
The authors declare no competing financial interest.
3
3
139.9, 134.3 (d, JCP = 19 Hz), 131.3 (d, JCP = 11 Hz), 130.4, 129.9,
129.8, 126.3, 30.5, 21.4; 31P NMR (162 MHz, CDCl3) δ −3.7; HRMS
m/z calcd for C29H28N2P [M + H]+ 435.1990, found 435.1991.
6-(Di-(3,5-dimethyl-4-methoxy)phenylphosphanyl)-12,13-dihy-
dro-5H-dibenzo[d,h][1,3]diazonine (29). A solution of phosphine
borane 26 (0.176 g, 0.328 mmol) in toluene (2 mL) was treated under
an Ar atmosphere with DABCO (0.147 g, 1.31 mmol) and stirred at
60 °C for 90 min. After cooling to rt, the reaction mixture was purified
by chromatography on SiO2 (5% EtOAc/hexanes) to afford phosphine
ACKNOWLEDGMENTS
■
J.A.M., E.R., and P.W. thank Drs. Steven Geib and Bhaskar
Godugu (University of Pittsburgh) for X-ray and HRMS
analyses, respectively. J.A.M. acknowledges financial support
from the University of Pittsburgh in the form of an Arts and
Sciences Fellowship. E.R. thanks the Chulalongkorn University
Dutsadi Phiphat Scholarship for financial support.
1
29 (0.112 g, 0.214 mmol, 65%) as a sticky oil: H NMR (400 MHz,
CDCl3) δ 7.60−7.29 (br m, 4 H), 6.89−6.50 (br m, 8 H), 6.25−6.10
(br s, 1 H), 3.80 (s, 6 H), 3.65−3.15 (br m, 2 H), 3.00−2.68 (br m, 2
H), 2.35 (s, 12 H); 13C NMR (100 MHz, CDCl3) δ 158.5, 156.7,
156.6, 135.2, 135.0, 131.7, 130.5, 129.5, 129.4, 126.3, 59.7, 31.4, 29.5,
16.3; 31P NMR (162 MHz, CDCl3) δ −3.2; HRMS m/z calcd for
C33H36N2O2P [M + H]+ 523.2514, found 523.2494.
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