Regiospecific Hydration of N-(Diphenylphosphinoyl)propargyl Amines: Synthesis of β-Amino Ketones by Au(III) Catalysis

Article abstract of DOI:10.1021/acs.joc.6b01111

A Au(III)-catalyzed regiospecific hydration of N-(diphenylphosphinoyl)propargyl amines has been developed to produce various β-amino ketones. These reactions are conducted in the presence of NaAuCl₄·2H₂O (10 mol %) in a mixed solvent of EtOH/H₂O/CH₂Cl₂ (4:1:1) at room temperature to give the products in 45-71% yield. The high enantiomeric purity of a chiral N-(diphenylphosphinoyl)propargyl amine (85% ee) is maintained after hydration, which makes this method useful for the asymmetric synthesis of chiral β-amino ketones. Reduction of a β-amino ketone product with Zn(BH₄)₂ gives a 1,3-amino alcohol with modest diastereoselectivity.

Full text of DOI:10.1021/acs.joc.6b01111

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Regiospecific Hydration of N‑(Diphenylphosphinoyl)propargyl
Amines: Synthesis of β‑Amino Ketones by Au(III) Catalysis
Jun Ying and Lin Pu*
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22904-4319, United States
S
* Supporting Information
ABSTRACT: A Au(III)-catalyzed regiospecific hydration of
N-(diphenylphosphinoyl)propargyl amines has been developed
to produce various β-amino ketones. These reactions are
conducted in the presence of NaAuCl4·2H2O (10 mol %) in a
mixed solvent of EtOH/H2O/CH2Cl2 (4:1:1) at room
temperature to give the products in 45−71% yield. The high
enantiomeric purity of a chiral N-(diphenylphosphinoyl)-
propargyl amine (85% ee) is maintained after hydration, which makes this method useful for the asymmetric synthesis of
chiral β-amino ketones. Reduction of a β-amino ketone product with Zn(BH4)2 gives a 1,3-amino alcohol with modest
diastereoselectivity.
can be readily synthesized from the reaction of N-(diphenyl-
phosphinoyl)imines with terminal alkynes, as shown in Scheme
2.6 In this reaction, the N-(diphenylphosphinoyl) group7 can
INTRODUCTION
■
Propargylic amines are versatile synthetic precursors to
nitrogen-containing pharmaceuticals, natural products, and
other biologically active compounds.1 For example, the alkyne
unit of a propargylic amine can be converted to a carbonyl
group by catalytic hydration.2 As shown in Scheme 1, hydration
Scheme 2. Synthesis of N-(Diphenylphosphinoyl)propargyl
Amines
Scheme 1. Hydration of the Propargylic Amine Triple Bond
not only increase the electrophilicity of the imine carbon but
also activate ZnMe2 to deprotonate the terminal alkynes for the
nucleophilic addition. Several chiral catalysts have also been
developed for this reaction for the asymmetric synthesis of
propargylic amines.8 The N-(diphenylphosphinoyl) group
employed in this reaction can be readily removed from the
product in the presence of aqueous hydrogen chloride at room
temperature. We propose to explore the use of the N-
(diphenylphosphinoyl) group of these propagylic amines to
direct the regioselective hydration of the alkyne unit. Herein,
we report the first example for the regiospecific hydration of N-
(diphenylphosphinoyl)propargyl amines to generate β-amino
ketones by using a Au(III) catalyst at room temperature. We
have also demonstrated that when an enantiomerically enriched
substrate is used, the high enantiomeric purity of the propargyl
amine is maintained in the hydration product.
of an internal alkyne unit of a propargylic amine in the presence
of a metal catalyst can generate both α- and β-amino ketones.
Although both α- and β-amino ketones are very useful for the
synthesis of many functional organic compounds, such as
amino alcohols and diamines, there are only limited reports on
the regioselective formation of these compounds from
hydration of propargylic amines. In several reports, Hg(II)
complexes were used, and the observed regioselective
formation of the β-amino ketones could be attributed to the
aryl group (R = aryl in Scheme 1) on the alkyne carbon of the
propargyl amines.3,4 There was one example on the hydration
of an alkyl-substituted propargyl amine (R = alkyl in Scheme 1)
catalyzed by using a mixture of AuClPPh3 and AgOTf as the
catalyst, which gave a β-amino ketone in good yield.5 The
propargyl amine used in this reaction contains an arylsulfonyl
group on the nitrogen.
Propargylic amines can be synthesized by nucleophilic
addition of alkynes to imines via deprotonation of terminal
alkynes.1 Among many propargylic amines investigated as
synthetic precursors, N-(diphenylphosphinoyl)propargyl
amines are particularly interesting. These types of compounds
Received: May 11, 2016
© XXXX American Chemical Society
A
DOI: 10.1021/acs.joc.6b01111
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Table 1. Screening of Catalysts and Reaction Conditions for the Hydration of 1a
a
entry
catalyst
AgNO3
solvent
temp (°C)
time (h)
yield (%)
1
2
MeOH/H2O (4:1)
rt
rt
20
20
20
20
20
12
20
20
20
20
20
20
nr
Cu(OAc)2
MeOH/H2O (4:1)
nr
3
Hg(OAc)2
CH3CN/H2O/DCM (4:1:1)
MeOH/H2O (3:1)
rt
trace
nr
4
Zeise’s dimer
Zeise’s dimer
Zeise’s dimer
NaAuCl4·2H2O
NaAuCl4·2H2O
NaAuCl4·2H2O
NaAuCl4·2H2O
Ph3PAuCl
rt
5
MeOH/H2O (3:1)
50
85
rt
complicated mixture
6
MeOH/H2O (3:1)
complicated mixture
7
EtOH/H2O (4:1)
50
62
54
10
nr
nr
8
EtOH/H2O/DCM (4:1:1)
EtOH/H2O/DCM (4:1:1)
EtOH/H2O/DCM (4:1:1)
EtOH/H2O/DCM (4:1:1)
EtOH/H2O/DCM (4:1:1)
rt
b
c
9
rt
10
11
12
rt
rt
Ph3PAuCl/AgSbF6
rt
a
b
Alkyne (0.1 mmol), EtOH/H2O/CH2Cl2 (4:1:1, 3 mL); 10 mol % of the catalyst was used unless indicated otherwise. 5 mol % of the catalyst was
c
used. 1 mol % of the catalyst was used.
RESULTS AND DISCUSSION
■
In order to conduct the hydration of the alkyne unit of N-
(diphenylphosphinoyl)propargyl amines, we investigated the
reaction of compound 1a with water in the presence of various
Lewis acid catalysts, and the results are summarized in Table 1.
In general, in order to maintain the N-(diphenylphosphinoyl)
group, we avoided the strongly acidic conditions often
employed in hydration. It shows that when AgNO3 or
Cu(OAc)2 was used, no reaction occurred (entries 1 and 2).
The reaction in the presence of Hg(OAc)2 at room
temperature gave only a trace amount of product (entry 3).
Previously, we reported that the Pt(II)-based Zeise’s dimer was
very effective for the regiospecific hydration of γ-hydroxy-α,β-
acetylenic esters.9 When 1a was treated with Zeise’s dimer at
room temperature, no reaction was observed (entry 4).
Increasing the temperature to 50 °C or refluxing at 85 °C led
to complicated product mixtures (entries 5 and 6). The gold
complex NaAuCl4 was previously reported to be effective for
the hydration of alkynes.10 We were delighted to find that this
gold complex also catalyzed the hydration of 1a to generate the
β-amino ketone product 2a in 50% yield at room temperature
in a mixed solvent of ethanol and water (4:1) (entry 7). The
yield in entry 5 was increased to 62% when methylene chloride
was added to improve the solubility of 1a (entry 8). In this
reaction, only the β-amino ketone product was obtained with
no observation of the α-amino ketone isomer. This conversion
represents the first example for the regiospecific hydration of N-
(diphenylphosphinoyl)propargyl amine to generate a β-amino
ketone. When the amount of NaAuCl4 was reduced to 5 or 1
mol %, the product yield was reduced (entries 9 and 10). We
also tested the use of a Au(I) catalyst, Ph3PAuCl, as well as its
combination with AgSbF6, but neither showed catalytic activity
under our reaction conditions (entries 11 and 12).11
Figure 1. N-(Diphenylphosphinoyl)propargyl amines 1a−1k prepared
from the reaction of alkynes with N-(diphenylphosphinoyl)imines.
summarized in Scheme 3. It shows that the electron-donating
Me-substituted propargylic amine 1b gives a yield higher than
that of compound 1c that contains an electron-withdrawing Br
substituent. The hydration of compounds 1d−1f containing a
linear alkyl group on the triple bond proceeds in good yields.
The reaction of the chlorine-substituted propargylic amine 1g
gave the desired product 2g in moderate yield (45%), which
could be attributed to side reactions of the alkyl chloride under
the reaction conditions. Compounds 1h−1j containing a
carbocycle on the triple bond and compound 1k containing a
vinyl group on the triple also gave good yields. We also tested
the hydration of a substrate with an aryl substituent on the
alkyne carbon (R1 = H and R2 = Ph), but no reaction was
observed.
We prepared a series of N-(diphenylphosphinoyl)amines,
1a−1k, as shown in Figure 1, using Bolm’s method6 from the
reaction of terminal alkynes with N-(diphenylphosphinoyl)-
imines in the presence of ZnMe2. These compounds were
subjected to the gold catalytic hydration conditions of entry 8
in Table 1 to generate β-amino ketones, and the results are
Previously, Hammond reported that 3-alkynoates such as 3
undergo a highly regioselective hydration in the presence of
NaAuCl4 to give the γ-ketone ester 4 in good yield (Scheme
4).10b,12 In this reaction, a Au(III)-promoted 5-endo-dig
cyclization intermediate 5 was proposed to account for the
observed regioselectivity.
B
DOI: 10.1021/acs.joc.6b01111
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Scheme 3. Gold-Catalyzed Hydration of N-
(Diphenylphosphinoyl)propargyl Amines 1a−1k
Scheme 5. Proposed Mechanism for the Gold-Catalyzed
Hydration of 1a
protonation and tautomerization gave the observed major
product, the β-amino ketone 2a. This mechanism indicates that
the phosphinoyl group of the propargylic amines can direct the
hydration to occur specifically at the 3-position of the starting
propargyl amine. An α,β-unsaturated ketone 8 was also
observed as the minor product (10−15% yield) from the
gold-catalyzed hydration. Formation of this compound could be
attributed to the result of the route b elimination from
intermediate 7.
Scheme 4. Regioselective Hydration of 3-Alkynoate 3
Although the mechanism proposed in Scheme 5 is
reasonable, we also cannot completely rule out another
pathway involving the formation of the 6-endo-dig cyclization
intermediate 9 and its subsequent hydrolysis, as shown in
Scheme 6. Additional study is necessary in order to distinguish
these two mechanisms.
In order to gain a better understanding of our Au(III)-
catalyzed reaction, we conducted the hydration of 1a in the
presence of H218O. The 13C and 31P NMR spectra of the
resulting product 2a demonstrate that the 18O was incorporated
into the ketone group but not in the phosphinoyl group, as an
upfield shift of the 13C NMR signal for the carbonyl carbon of
2a from δ 210.279 to δ 210.228 was observed, but with no shift
for the 31P NMR signal. The high-resolution mass spectrum of
the product isolated from the hydrolysis in the presence of
H218O gave the molecular ion for 2a + H+ at m/z = 408.1967
(calcd for C25H29NP16O18O + H+ 408.1978), indicating the
incorporation of one 18O atom. In the mass spectrum, the base
peak is observed for the fragment 2a − CH2C(18O)C4H9 at m/
z = 306.1042 (calcd for C19H17N16OP 306.1048) with
insignificant 18O incorporation. Thus, the mass spectroscopic
study confirms that observed by 31P and 13C NMR analyses,
and the carbonyl oxygen of the ketone product is derived from
water.
Scheme 6. Another Possible Pathway for the Gold-Catalyzed
Hydration of 1a
On the basis of the above experimental results, a mechanism
for the Au(III)-catalyzed hydration of 1a is proposed in Scheme
5. The chelate coordination of the phosphinoyl group and the
alkyne unit to the Au(III) center can generate the intermediate
6. Nucleophilic addition of water to the activated alkyne unit of
6 followed by an enol-keto tautomerization could give the
intermediate 7. In this step, the water attack at the C3 position
should be more favorable than that at the C2 position because
the resulting six-membered ring intermediate should be more
favorable than a seven-membered ring intermediate. Inter-
mediate 7 has two possible pathways, routes a and b, to
eliminate the Au(III) unit. The route a elimination followed by
The regiospecific hydration of the N-(diphenylphosphinoyl)-
propargyl amines prompted us to study the use of an optically
active substrate for this reaction. Recently, we developed an
asymmetric addition of aliphatic alkynes to N-(diphenylphos-
phinoyl)imines, affording the N-(diphenylphosphinoyl)-
propargyl amines with good enantioselectivity.13 As shown in
Scheme 6, (S)-1a was obtained with 85% ee at room
temperature from this asymmetric alkyne addition by using a
partially hydrogenated 1,1′-bi-2-naphthol-based catalyst in the
presence of ZnEt2 and Ti(OiPr)4. Applying the conditions for
the gold-catalyzed hydration to this optically active propargylic
amine led to the formation of the corresponding optically active
C
DOI: 10.1021/acs.joc.6b01111
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Scheme 7. Preparation of the Optically Active (S)-1a and Its Conversion to the β-Amino Ketone (R)-2a
β-amino ketone (R)-2a with 85% ee (Scheme 7). This result
demonstrates that the gold-catalyzed hydration of the
propargylic amines can maintain the enantiomeric purity of
the propargylic amine. Thus, this strategy provides an efficient
method for the asymmetric synthesis of chiral β-amino ketones.
We also tested the reduction of a β-amino ketone product
obtained from the hydration of a N-(diphenylphosphinoyl)-
propargyl amine to generate a 1,3-amino alcohol. As shown in
Scheme 8, when compound 2k was treated with Zn(BH4)2, in
EXPERIMENTAL SECTION
■
General Data. Reactions were carried out under nitrogen. All
commercial chemicals were used without further purification unless
otherwise noted. Zinc reagents and catalysts were purchased and
stored under dry nitrogen atmosphere. Toluene and tetrahydrofuran
were distilled over sodium and benzophenone under nitrogen.
Dichloromethane was dried by passing through activated alumina
columns under nitrogen. All the NMR spectra were obtained in CDCl3
unless indicated otherwise.
General Procedure for the Syntheses of the N-(Diphenyl-
phosphinoyl)propargyl Amines 1. Under nitrogen, an alkyne (2
equiv) was added into a dry 100 mL flask and dissolved in toluene (30
mL). Me2Zn (1.67 mL, 1.2 M in toluene, 2 equiv) was then added, and
the mixture was stirred at room temperature for 30 min. Then, a
solution of N-(diphenylphosphinoyl)imine (1 mmol, 1 equiv) in
toluene (5 mL) was added, and the reaction temperature was increased
to 70 °C and stirred for 18 h. The reaction was quenched with the
addition of water (20 mL) and extracted with dichloromethane (3 ×
20 mL). The organic phase was washed with brine (20 mL) and dried
with anhydrous Na2SO4, filtered, and concentrated by rotary
evaporation. The crude mixture was purified by flash column
chromatography on silica gel eluted with hexanes/ethyl acetate (1/
1) to give N-(diphenylphosphinoyl)propargyl amine products 1 in
70−90% yield.
Characterization of the Propargylic N-(Diphenylphos-
phinoyl)amines 1. P,P-Diphenyl-N-(1-phenylhept-2-yn-1-yl)-
phosphinic Amide, 1a: White solid, mp 116−118 °C, 329 mg
(prepared from 1 mmol imine), 85% yield; 1H NMR (600 MHz,
CDCl3) δ 8.03 (m, 2H), 7.82 (m, 2H), 7.60 (d, 2H, J = 7.8 Hz), 7.52
(t, 1H, J = 7.2 Hz), 7.46 (m, 3H), 7.37 (m, 2H), 7.32 (t, 2H, J = 7.2
Hz), 7.25 (t, 1H, J = 6.6 Hz), 5.13 (t, 1H, J = 10.2 Hz), 3.41 (t, 1H, J =
9 Hz), 2.21 (t, 2H, J = 7.2 Hz), 1.48 (m, 2H), 1.41 (m, 2H), 0.91 (t,
3H, J = 7.8 Hz); 13C{1H} NMR (150 MHz, CDCl3) δ 141.0 (d, J = 4.7
Hz), 132.7 (d, J = 9.8 Hz), 131.9, 131.8, 128.5, 128.4 (d, J = 11.9 Hz),
127.7, 127.2, 86.2, 79.7 (d, J = 6.2 Hz), 46.8, 30.7, 22.0, 18.5, 13.6.
These data are consistent with those reported.8d
P,P-Diphenyl-N-(1-(p-tolyl)hept-2-yn-1-yl)phosphinic Amide, 1b:
White solid, mp 138−140 °C, 153 mg (prepared from 0.44 mmol
imine), 87% yield; 1H NMR (600 MHz, CDCl3) δ 8.02 (m, 2H), 7.82
(m, 2H), 7.52 (m, 1H), 7.47 (m, 5H), 7.38 (m, 2H), 7.12 (d, 2H, J =
7.8 Hz), 5.09 (t, 1H, J = 9.6 Hz), 3.37 (t, 1H, J = 9 Hz), 2.31 (s, 3H),
2.19 (t, 2H, J = 7.2 Hz), 1.47 (m, 2H), 1.40 (m, 2H), 0.91 (t, 3H, J =
7.2 Hz); 13C{1H} NMR (150 MHz, CDCl3) δ 138.2 (d, J = 4.7 Hz),
137.4, 132.7 (d, J = 9.8 Hz), 131.9, 131.8, 129.1, 128.4 (d, J = 12.6
Hz), 127.1, 86.0, 79.8 (d, J = 6 Hz), 46.6, 30.7, 22.0, 21.1, 18.5, 13.6;
HRMS [ESI(TOF)] calcd for C26H29NOP [M + H+] 402.1987; found
402.1985.
Scheme 8. Reduction of the β-Amino Ketone 2k with
Zn(BH4)2
situ generated from the reaction of NaBH4 with ZnCl2,14 the
1,3-amino alcohol product 10 was obtained in 86% yield with a
2.3:1 diastereoselectivity. The modest diastereoselectivity of
this reaction can be attributed to the chelate interaction of the
carbonyl group and the phosphinoylamine groups of 2k with
the Zn(II) center of the reducing agent. When NaBH4 or
LiBH4 was used for the reduction of several of the β-N-
(diphenylphosphinoyl)amino ketones, only a 1:1 mixture of the
diastereomeric amino alcohol products was observed. The
reaction using Zn(BH4)2 indicates that it is possible to conduct
a diastereoselective reduction of β-amino ketones to generate
1,3-amino alcohols. Further enhancement of the diastereose-
lectivity of this conversion will be explored.
CONCLUSIONS
■
We have discovered that a simple Au(III) complex can catalyze
the regiospecific hydration of N-(diphenylphosphinoyl)-
propargyl amines to generate β-amino ketones under very
mild conditions. In this reaction, the N-diphenylphosphinoyl
group of the substrates should have directed the hydration to
occur at the specific alkyne carbon of the propargyl amines. We
have also demonstrated that the high enantiomeric purity of a
chiral N-(diphenylphosphinoyl)propargyl amine can be main-
tained during the hydration to generate the optically active β-
amino ketone. This strategy in combination with the
asymmetric alkyne addition to N-(diphenylphosphinoyl)imines
provides a very convenient way for the asymmetric synthesis of
chiral β-amino ketones that are useful in organic synthesis.
Reduction of a β-amino ketone with Zn(BH4)2 gives a 1,3-
amino alcohol with modest diastereoselectivity.
N-(1-(4-Bromophenyl)hept-2-yn-1-yl)-P,P-diphenylphosphinic
Amide, 1c: White solid, mp 140−143 °C, 145.4 mg (prepared from
0.39 mmol imine), 80% yield; 1H NMR (600 MHz, CDCl3) δ 8.01 (m,
2H), 7.79 (m, 2H), 7.53 (m, 1H), 7.48 (m, 5H), 7.43 (m, 2H), 7.38
(m, 2H), 5.08 (t, 1H, J = 9 Hz), 3.44 (t, 1H, J = 7.8 Hz), 2.21 (m, 2H),
1.48 (m, 2H), 1.40 (m, 2H), 0.91 (t, 3H, J = 7.2 Hz); 13C{1H} NMR
(150 MHz, CDCl3) δ 140.1 (d, J = 3.8 Hz), 132.6 (d, J = 9.9 Hz),
132.0 (d, J = 10.5 Hz), 131.7 (d, J = 9.8 Hz), 131.5, 129.1, 128.4 (d, J
= 12.9 Hz), 121.7, 86.6, 79.1 (d, J = 6.9 Hz), 46.4, 30.6, 22.0, 18.4,
13.6; HRMS [ESI(TOF)] calcd for C25H26NOPBr [M + H+]
466.0935; found 466.0932.
D
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P,P-Diphenyl-N-(1-phenyloct-2-yn-1-yl)phosphinic Amide, 1d:
White solid, mp 120−122 °C, 313 mg (prepared from 1 mmol
imine), 78% yield; 1H NMR (600 MHz, CDCl3) δ 8.03 (m, 2H), 7.82
(m, 2H), 7.60 (d, 2H, J = 7.8 Hz), 7.51 (m, 1H), 7.45 (m, 3H), 7.37
(m, 2H), 7.32 (t, 2H, J = 7.2 Hz), 7.24 (m, 1H), 5.13 (t, 1H, J = 9.6
Hz), 3.43 (t, 1H, J = 9 Hz), 2.20 (m, 2H), 1.50 (m, 2H), 1.35 (m, 4H),
0.90 (t, 3H, J = 6.6 Hz); 13C{1H} NMR (150 MHz, CDCl3) δ 141.0
(d, J = 4.5 Hz), 132.7 (d, J = 9.8 Hz), 131.9 (d, J = 7.5 Hz), 131.85 (d,
J = 9.8 Hz), 128.45 (d, J = 3.6 Hz), 128.4, 127.7, 127.2, 86.3, 79.7 (d, J
= 6.2 Hz), 46.8, 31.1, 28.3, 22.2, 18.8, 14.0; HRMS [ESI(TOF)] calcd
for C26H29NOP [M + H+] 402.1987; found 402.1971.
P,P-Diphenyl-N-(1-phenylnon-2-yn-1-yl)phosphinic Amide, 1e:
White solid, mp 110−112 °C, 332 mg (prepared from 1 mmol
imine), 80% yield; 1H NMR (600 MHz, CDCl3) δ 8.03 (m, 2H), 7.82
(m, 2H), 7.60 (d, 2H, J = 8.4 Hz), 7.52 (m, 1H), 7.46 (m, 3H), 7.37
(m, 2H), 7.32 (t, 2H, J = 7.2 Hz), 7.25 (m, 1H), 5.13 (t, 1H, J = 9.6
Hz), 3.41 (t, 1H, J = 9 Hz), 2.20 (m, 2H), 1.49 (m, 2H), 1.38 (m, 2H),
1.29 (m, 4H), 0.88 (t, 3H, J = 7.2 Hz); 13C{1H} NMR (150 MHz,
CDCl3) δ 141.0 (d, J = 4.7 Hz), 132.7 (d, J = 9.9 Hz), 131.9 (d, J = 7.4
Hz), 131.8 (d, J = 9.6 Hz), 128.5, 128.4 (d, J = 12.8 Hz), 127.7, 127.2,
86.3, 79.7 (d, J = 6.2 Hz), 46.8, 31.3, 28.6, 28.5, 22.5, 18.8, 14.0;
HRMS [ESI(TOF)] calcd for C27H31NOP [M + H+] 416.2143; found
416.2141.
N-(1,5-Diphenylpent-2-yn-1-yl)-P,P-diphenylphosphinic Amide,
1f: White solid, mp 148−150 °C, 326 mg (prepared from 1 mmol
imine), 75% yield; 1H NMR (600 MHz, CDCl3) δ 7.99 (m, 2H), 7.81
(m, 2H), 7.51 (m, 3H), 7.45 (m, 3H), 7.38 (m, 2H), 7.27 (m, 5H),
7.20 (m, 3H), 5.10 (t, 1H, J = 9.6 Hz), 3.39 (t, 1H, J = 9 Hz), 2.80 (m,
2H), 2.51 (m, 2H); 13C{1H} NMR (150 MHz, CDCl3) δ 140.8 (d, J =
4.8 Hz), 140.6, 132.6 (d, J = 9.8 Hz), 131.92 (d, J = 7.7 Hz), 131.88 (d,
J = 9.6 Hz), 128.5 (d, J = 1.7 Hz), 128.46, 128.38, 128.36, 127.7, 127.2,
126.3, 85.4, 80.5 (d, J = 6 Hz), 46.8, 34.8, 20.9; HRMS [ESI(TOF)]
calcd for C29H27NOP [M + H+] 436.1830; found 436.1818.
2H), 7.81 (m, 2H), 7.62 (d, 2H, J = 7.8 Hz), 7.52 (m, 1H), 7.47 (m,
3H), 7.38 (m, 2H), 7.32 (t, 2H, J = 7.2 Hz), 7.25 (m, 1H), 5.15 (t, 1H,
J = 9.6 Hz), 3.39 (t, 1H, J = 9 Hz), 2.42 (m, 1H), 1.79 (m, 2H), 1.70
(m, 2H), 1.51 (m, 1H), 1.43 (m, 2H), 1.31 (m, 3H); 13C{1H} NMR
(150 MHz, CDCl3) δ 141.0 (d, J = 4.2 Hz), 132.8 (d, J = 9.9 Hz),
131.9 (d, J = 10.1 Hz), 131.7 (d, J = 9.8 Hz), 128.4, 128.3, 127.6,
127.3, 90.3, 79.6 (d, J = 6.3 Hz), 46.8, 32.5, 29.1, 25.9, 24.8; HRMS
[ESI(TOF)] calcd for C27H29NOP [M + H+] 414.1987; found
414.1982.
N-(3-(Cyclohex-1-en-1-yl)-1-phenylprop-2-yn-1-yl)-P,P-diphenyl-
phosphinic Amide, 1k: White solid, mp 154−156 °C, 337 mg
(prepared from 1 mmol imine), 82% yield; 1H NMR (600 MHz,
CDCl3) δ 8.04 (m, 2H), 7.81 (m, 2H), 7.61 (d, 2H, J = 7.2 Hz), 7.52
(m, 1H), 7.46 (m, 3H), 7.37 (m, 2H), 7.32 (d, 2H, J = 7.8 Hz), 7.25
(m, 1H), 6.09 (s, 1H), 5.26 (t, 1H, J = 9.6 Hz), 3.46 (t, 1H, J = 9 Hz),
2.09 (d, 4H, J = 6 Hz), 1.62 (m, 4H); 13C{1H} NMR (150 MHz,
CDCl3) δ 140.7 (d, J = 4.4 Hz), 135.1, 132.8 (d, J = 9.8 Hz), 131.9 (d,
J = 7.8 Hz), 131.8 (d, J = 9.8 Hz), 128.5, 128.4 (d, J = 12.8 Hz), 127.8,
127.3, 120.2, 87.4, 86.0 (d, J = 6.3 Hz), 47.1, 29.1, 25.6, 22.2, 21.5;
HRMS [ESI(TOF)] calcd for C27H27NOP [M + H+] 412.1830; found
412.1829.
General Procedure for the Gold-Catalyzed Hydration of N-
(Diphenylphosphinoyl)propargyl Amines 1. Under nitrogen,
NaAuCl4·2H2O (10 mol %) was added to a flask. A solution of the
N-(diphenylphosphinoyl)propargyl amine 1 (1 equiv) in EtOH/H2O/
CH2Cl2 (4:1:1, 3 mL) was then added, and the reaction mixture was
stirred at room temperature for 20 h. Water (3 mL) was added, and
methylene chloride (3 × 5 mL) was used for extraction. The combined
organic layer was dried with anhydrous Na2SO4, filtered, and
concentrated by rotary evaporation. The crude mixture was purified
by flash column chromatography on silica gel eluted with hexanes/
ethyl acetate (1:1 to 1:5) to give the β-amino ketone products 2 in
45−71% yield.
Characterization of the Racemic β-Amino Ketone Products
2. N-(3-Oxo-1-phenylheptyl)-P,P-diphenylphosphinic Amide, 2a:
White solid, mp 155−157 °C, 116.3 mg (prepared from 0.465
N-(6-Chloro-1-phenylhex-2-yn-1-yl)-P,P-diphenylphosphinic
Amide, 1g: White solid, mp 107−109 °C, 366 mg (prepared from 1
1
mmol imine), 90% yield; H NMR (600 MHz, CDCl3) δ 8.00 (m,
1
mmol amine), 62% yield; H NMR (600 MHz, CDCl3) δ 7.80 (m,
2H), 7.82 (m, 2H), 7.56 (d, 2H, J = 7.8 Hz), 7.52 (m, 1H), 7.47 (m,
3H), 7.39 (m, 2H), 7.33 (t, 2H, J = 7.8 Hz), 7.26 (t, 1H, J = 7.2 Hz),
5.14 (t, 1H, J = 9.6 Hz), 3.61 (t, 2H, J = 6.6 Hz), 3.42 (t, 1H, J = 8.4
Hz), 2.39 (m, 2H), 1.92 (m, 2H); 13C{1H} NMR (150 MHz, CDCl3)
δ 140.7 (d, J = 4.8 Hz), 132.5 (d, J = 9.8 Hz), 132.0 (d, J = 6.9 Hz),
131.8 (d, J = 9.8 Hz), 128.6, 128.4 (d, J = 12.6 Hz), 127.9, 127.1, 84.1,
80.8 (d, J = 5.6 Hz), 46.7, 43.7, 31.2, 16.2; HRMS [ESI(TOF)] calcd
for C24H24NOPCl [M + H+] 408.1284; found 408.1280.
4H), 7.43 (m, 4H), 7.27 (m, 7H), 4.58 (m, 1H), 4.47 (s, 1H), 3.14 (m,
2H), 2.24 (m, 1H), 2.19 (m, 1H), 1.36 (m, 2H), 1.13 (m, 2H), 0.78 (t,
3H, J = 7.2 Hz); 13C{1H} NMR (150 MHz, CDCl3) δ 210.2, 142.4 (d,
J = 7.2 Hz), 132.5 (d, J = 9.6 Hz), 131.8 (dd, J = 6.3, 2.6 Hz), 131.6 (d,
J = 9.5 Hz), 128.5 (dd, J = 12.5, 9.3 Hz), 128.4, 127.1, 126.4, 51.8,
50.1, 43.5, 25.3, 22.0, 13.7; HRMS [ESI(TOF)] calcd for C25H29NO2P
[M + H+] 406.1936; found 406.1932.
N-(3-Oxo-1-(p-tolyl)heptyl)-P,P-diphenylphosphinic Amide, 2b:
White solid, mp 151−153 °C, 141 mg (prepared from 0.563 mmol
amine), 60% yield; 1H NMR (600 MHz, CDCl3) δ 7.81 (m, 4H), 7.43
(m, 4H), 7.34 (m, 2H), 7.15 (d, 2H, J = 7.8 Hz), 7.08 (d, 2H, J = 7.8
Hz), 4.55 (m, 1H), 4.31 (m, 1H), 3.13 (d, 2H, J = 5.4 Hz), 2.30 (s,
3H), 2.25 (m, 1H), 2.18 (m, 1H), 1.37 (m, 2H), 1.14 (m, 2H), 0.79 (t,
3H, J = 7.2 Hz); 13C{1H} NMR (150 MHz, CDCl3) δ 210.2, 139.4 (d,
J = 7.4 Hz), 136.7, 132.5 (d, J = 9.5 Hz), 131.8 (dd, J = 4.4, 2.6 Hz),
131.6 (d, J = 9.5 Hz), 129.1, 128.4 (dd, J = 12.6, 5.3 Hz), 126.2, 51.5,
50.2 (d, J = 2 Hz), 43.5, 25.3, 22.1, 21.0, 13.7; HRMS [ESI(TOF)]
calcd for C26H31NO2P [M + H+] 420.2092; found 420.2086.
N-(1-(4-Bromophenyl)-3-oxoheptyl)-P,P-diphenylphosphinic
Amide, 2c: White solid, mp 163−165 °C, 114 mg (prepared from
N-(3-Cyclopropyl-1-phenylprop-2-yn-1-yl)-P,P-diphenylphos-
phinic Amide, 1h: White solid, mp 178−180 °C, 260 mg (prepared
from 1 mmol imine), 70% yield; 1H NMR (600 MHz, CDCl3) δ 8.01
(m, 2H), 7.80 (m, 2H), 7.56 (d, 2H, J = 7.8 Hz), 7.53 (t, 1H, J = 7.2
Hz), 7.47 (m, 3H), 7.38 (m, 2H), 7.31 (t, 2H, J = 7.8 Hz), 7.25 (t, 1H,
J = 5.4 Hz), 5.10 (t, 1H, J = 9.6 Hz), 3.38 (t, 1H, J = 8.4 Hz), 1.24 (m,
1H), 0.74 (m, 2H), 0.63 (m, 2H); 13C{1H} NMR (150 MHz, CDCl3)
δ 140.9 (d, J = 4.7 Hz), 132.7 (d, J = 9.8 Hz), 131.9 (d, J = 8.7 Hz),
131.8 (d, J = 9.8 Hz), 128.5, 128.4 (d, J = 12.6 Hz), 127.7, 127.2, 89.2,
74.8 (d, J = 6 Hz), 46.8, 8.1, −0.5. These data are consistent with those
reported.8d
N-(3-Cyclopentyl-1-phenylprop-2-yn-1-yl)-P,P-diphenylphos-
phinic Amide, 1i: White solid, mp 128−130 °C, 287 mg (prepared
from 1 mmol imine), 72% yield; 1H NMR (600 MHz, CDCl3) δ 8.04
(m, 2H), 7.80 (m, 2H), 7.60 (d, 2H, J = 7.8 Hz), 7.52 (m, 1H), 7.45
(m, 3H), 7.37 (m, 2H), 7.32 (t, 2H, J = 7.2 Hz), 7.24 (m, 1H), 5.15 (t,
1H, J = 9.6 Hz), 3.42 (t, 1H, J = 9 Hz), 2.64 (m, 1H), 1.88 (m, 2H),
1.71 (m, 2H), 1.57 (m, 4H); 13C{1H} NMR (150 MHz, CDCl3) δ
141.0 (d, J = 4.4 Hz), 132.7 (d, J = 9.9 Hz), 131.9 (d, J = 9.8 Hz),
131.7 (d, J = 9.9 Hz), 128.4, 128.3 (d, J = 11.9 Hz), 127.6, 127.3, 90.4,
79.2 (d, J = 6 Hz), 46.8, 33.7 (d, J = 1.2 Hz), 30.2, 24.9; HRMS
[ESI(TOF)] calcd for C26H27NOP [M + H+] 400.1830; found
400.1828.
1
0.491 mmol amine), 48% yield; H NMR (600 MHz, CDCl3) δ 7.81
(m, 2H), 7.75 (m, 2H), 7.43 (m, 6H), 7.34 (m, 2H), 7.15 (d, 2H, J =
8.4 Hz), 4.51 (m, 1H), 4.46 (m, 1H), 3.12 (m, 2H), 2.27 (m, 1H),
2.19 (m, 1H), 1.38 (m, 2H), 1.15 (m, 2H), 0.80 (t, 3H, J = 7.2 Hz);
13C{1H} NMR (150 MHz, CDCl3) δ 210.1, 141.5 (d, J = 6.9 Hz),
132.3 (d, J = 9.6 Hz), 131.9 (dd, J = 5.6, 2.7 Hz), 131.6 (d, J = 9.5 Hz),
131.5, 128.5 (dd, J = 12.6, 7.5 Hz), 128.2, 121.0, 51.2, 49.7 (d, J = 2.3
Hz), 43.5, 25.3, 22.1, 13.7; HRMS [ESI(TOF)] calcd for
C25H28NO2PBr [M + H+] 484.1041; found 484.1028.
N-(3-Oxo-1-phenyloctyl)-P,P-diphenylphosphinic Amide, 2d:
White solid, mp 157−158 °C, 158 mg (prepared from 0.581 mmol
amine), 65% yield; 1H NMR (600 MHz, CDCl3) δ 7.83 (m, 2H), 7.78
(m, 2H), 7.46 (m, 1H), 7.40 (m, 3H), 7.32 (m, 2H), 7.27 (d, 4H, J =
N-(3-Cyclohexyl-1-phenylprop-2-yn-1-yl)-P,P-diphenylphosphinic
Amide, 1j: White solid, mp 155−157 °C, 310 mg (prepared from 1
1
mmol imine), 75% yield; H NMR (600 MHz, CDCl3) δ 8.05 (m,
E
DOI: 10.1021/acs.joc.6b01111
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The Journal of Organic Chemistry
Featured Article
4.8 Hz), 7.20 (m, 1H), 4.58 (m, 1H), 4.45 (m, 1H), 3.13 (d, 2H, J =
5.4 Hz), 2.24 (m, 1H), 2.16 (m, 1H), 1.38 (m, 2H), 1.17 (m, 2H),
1.07 (m, 2H), 0.79 (t, 3H, J = 7.2 Hz); 13C{1H} NMR (150 MHz,
CDCl3) δ 210.3, 142.4 (d, J = 7.2 Hz), 132.5 (d, J = 9.5 Hz), 131.8
(dd, J = 6.3, 2.6 Hz), 131.6 (d, J = 9.5 Hz), 128.5 (dd, J = 12.5, 9 Hz),
128.4, 127.1, 126.4, 51.7, 50.0 (d, J = 2.1 Hz), 43.8, 31.1, 22.9, 22.3,
13.8; HRMS [ESI(TOF)] calcd for C26H31NO2P [M + H+] 420.2092;
found 420.2087.
N-(3-Oxo-1-phenylnonyl)-P,P-diphenylphosphinic Amide, 2e:
White solid, mp 143−145 °C, 140.3 mg (prepared from 0.54 mmol
amine), 60% yield; 1H NMR (600 MHz, CDCl3) δ 7.83 (m, 2H), 7.78
(m, 2H), 7.46 (m, 1H), 7.40 (m, 3H), 7.33 (m, 2H), 7.26 (d, 4H, J =
4.2 Hz), 7.20 (m, 1H), 4.57 (m, 1H), 4.48 (s, 1H), 3.13 (d, 2H, J = 5.4
Hz), 2.23 (m, 1H), 2.18 (m, 1H), 1.37 (m, 2H), 1.19 (m, 2H), 1.11
(m, 4H), 0.81 (t, 3H, J = 7.2 Hz); 13C{1H} NMR (150 MHz, CDCl3)
δ 210.3, 142.4 (d, J = 7.2 Hz), 132.5 (d, J = 9.6 Hz), 131.8 (dd, J = 6.3,
2.6 Hz), 131.6 (d, J = 9.5 Hz), 128.5 (dd, J = 12.3, 9.2 Hz), 128.4,
127.1, 126.4, 51.8, 50.1 (d, J = 2.1 Hz), 43.8, 31.5, 28.6, 23.2, 22.4,
14.0; HRMS [ESI(TOF)] calcd for C27H33NO2P [M + H+] 434.2249;
found 434.2250.
N-(3-Oxo-1,5-diphenylpentyl)-P,P-diphenylphosphinic Amide, 2f:
White solid, mp 147−149 °C, 149 mg (prepared from 0.568 mmol
amine), 58% yield; 1H NMR (600 MHz, CDCl3) δ 7.82 (m, 4H), 7.48
(t, 1H, J = 7.2 Hz), 7.41 (m, 3H), 7.34 (m, 2H), 7.23 (m, 7H), 7.14 (t,
1H, J = 7.2 Hz), 7.02 (d, 2H, J = 7.8 Hz), 4.59 (m, 1H), 4.38 (s, 1H),
3.15 (d, 2H, J = 4.8 Hz), 2.73 (t, 2H, J = 7.2 Hz), 2.61 (m, 1H), 2.52
(m, 1H); 13C{1H} NMR (150 MHz, CDCl3) δ 208.9, 142.3 (d, J = 7.1
Hz), 140.6, 132.5 (d, J = 9.5 Hz), 131.9 (dd, J = 5.9, 2.6 Hz), 131.6 (d,
J = 9.5 Hz), 128.56 (d, J = 12.5 Hz), 128.50, 128.4, 128.2, 127.2, 126.4,
126.0, 51.7, 50.4, 45.2, 29.2; HRMS [ESI(TOF)] calcd for
C29H29NO2P [M + H+] 454.1936; found 454.1925.
NMR (150 MHz, CDCl3) δ 213.2, 142.5 (d, J = 7.1 Hz), 132.5 (d, J =
9.6 Hz), 131.8 (dd, J = 6.2, 2.7 Hz), 131.6 (d, J = 9.6 Hz), 128.5 (dd, J
= 12.5, 9 Hz), 128.3, 127.0, 126.4, 51.8, 51.4, 48.0, 27.7 (d, J = 10.2
Hz), 25.7, 25.4; HRMS [ESI(TOF)] calcd for C27H31NO2P [M + H+]
432.2092; found 432.2089.
N-(3-(Cyclohex-1-en-1-yl)-3-oxo-1-phenylpropyl)-P,P-diphenyl-
phosphinic Amide, 2k: White solid, mp 115−118 °C, 172 mg
1
(prepared from 0.616 mmol amine), 65% yield; H NMR (600 MHz,
CDCl3) δ 7.84 (m, 2H), 7.80 (m, 2H), 7.45 (m, 1H), 7.39 (m, 3H),
7.32 (m, 2H), 7.28 (m, 2H), 7.26 (m, 2H), 7.18 (t, 1H, J = 7.2 Hz),
6.77 (s, 1H), 4.62 (m, 1H), 4.54 (m, 1H), 3.43 (dd, 1H, J = 16.8, 4.2
Hz), 3.34 (dd, 1H, J = 15.6, 6 Hz), 2.12 (m, 2H), 2.04 (m, 2H), 1.50
(m, 4H); 13C{1H} NMR (150 MHz, CDCl3) δ 199.7, 142.7 (d, J = 6.9
Hz), 141.1, 139.3, 132.4 (d, J = 9.5 Hz), 131.8 (d, J = 2.7 Hz), 131.7
(d, J = 9.6 Hz), 128.4 (dd, J = 12.5, 6.8 Hz), 128.3, 126.9, 126.5, 52.3,
44.7 (d, J = 2.3 Hz), 26.0, 22.7, 21.7, 21.3; HRMS [ESI(TOF)] calcd
for C27H29NO2P [M + H+] 430.1936; found 430.1938.
Characterization of the Chiral β-Amino Ketone Products (R)-
2a. (R)-N-(3-Oxo-1-phenylheptyl)-P,P-diphenylphosphinic Amide,
(R)-2a: White solid, mp 155−157 °C, 125.6 mg (prepared from
0.517 mmol amine), 60% yield; 85% ee determined by HPLC analysis,
CHIRALCEL OD-H column, 90:10 hexanes/iPrOH, flow rate = 1.0
mL/min, λ = 230 nm; retention time, tmajor = 7.9 min, tminor = 14.4
min; [α]D23 = −66.8 (c = 1.45, CHCl3); 1H NMR (600 MHz, CDCl3)
δ 7.80 (m, 4H), 7.43 (m, 4H), 7.27 (m, 7H), 4.58 (m, 1H), 4.47 (s,
1H), 3.14 (m, 2H), 2.24 (m, 1H), 2.19 (m, 1H), 1.36 (m, 2H), 1.13
(m, 2H), 0.78 (t, 3H, J = 7.2 Hz); 13C{1H} NMR (150 MHz, CDCl3)
δ 210.2, 142.4 (d, J = 7.2 Hz), 132.5 (d, J = 9.6 Hz), 131.8 (dd, J = 6.3,
2.6 Hz), 131.6 (d, J = 9.5 Hz), 128.5 (dd, J = 12.5, 9.3 Hz), 128.4,
127.1, 126.4, 51.8, 50.1, 43.5, 25.3, 22.0, 13.7; HRMS [ESI(TOF)]
calcd for C25H29NO2P [M + H+] 406.1936; found 406.1932.
Reduction of the β-Amino Ketone 2k with Zn(BH4)2. Under
nitrogen, the β-amino ketone 2k (0.152 mmol, 65.1 mg, 1 equiv) was
dissolved in THF (2.0 mL) and cooled to −40 °C. Zn(BH4)2 (0.76
mmol, 0.3 M in THF, 2.5 mL, 5 equiv) was added dropwise, and the
reaction mixture was stirred for 1 h at −40 °C. Then, the reaction
mixture was warmed to 0 °C and stirred for another hour. Water (2.0
mL) was added to quench the reaction at 0 °C, and methylene
chloride (3 × 4 mL) was then used for extraction. The organic phase
was dried with anhydrous Na2SO4, filtered, and concentrated by rotary
evaporation. The crude mixture was purified by flash column
chromatography on silica gel eluted with hexanes/ethyl acetate (1:1)
to give the 1,3-amino alcohol 10 as a colorless oil in 86% yield (56.3
mg). 1H NMR analysis showed a 2.3:1 diastereomeric ratio: 1H NMR
(600 MHz, CDCl3) δ 7.85 (m, 2H), 7.70 (m, 2H), 7.50 (t, 1H, J = 7.8
Hz), 7.42 (m, 3H), 7.27 (m, 5H), 7.13 (d, 2H, J = 7.2 Hz), 5.67 (s,
1H), 4.42 (m, 1H), 4.33 (d, 1H, J = 10.2 Hz), 3.45 (t, 1H, J = 9.6 Hz),
1.97 (m, 5H), 1.77 (m, 1H), 1.53 (m, 5H); 13C{1H} NMR (150 MHz,
CDCl3) δ 144.3 (d, J = 6.2 Hz), 139.5, 132.8 (d, J = 9.9 Hz), 132.0
(dd, J = 30.2, 2.4 Hz), 131.5 (d, J = 9.8 Hz), 128.5, 128.4 (dd, J = 52.1,
12.5 Hz), 126.9, 126.0, 121.7, 70.8, 52.3, 45.5, 24.9, 24.6, 22.7, 22.6;
HRMS [ESI(TOF)] calcd for C27H30NO2PNa [M + Na+] 454.1912;
found 454.1906.
N-(6-Chloro-3-oxo-1-phenylhexyl)-P,P-diphenylphosphinic
Amide, 2g: White solid, mp 137−140 °C, 172 mg (prepared from
1
0.744 mmol amine), 45% yield; H NMR (600 MHz, CDCl3) δ 7.82
(m, 2H), 7.78 (m, 2H), 7.43 (m, 4H), 7.34 (m, 2H), 7.27 (m, 4H),
7.22 (m, 1H), 4.59 (m, 1H), 4.31 (s, 1H), 3.39 (dt, 2H, J = 6.0, 1.8
Hz), 3.16 (d, 2H, J = 6.0 Hz), 2.47 (m, 1H), 2.39 (m, 1H), 1.87 (m,
2H); 13C{1H} NMR (150 MHz, CDCl3) δ 208.5, 142.2 (d, J = 7.1
Hz), 132.5 (d, J = 9.6 Hz), 131.9 (dd, J = 6.5, 2.6 Hz), 131.6 (d, J = 9.3
Hz), 128.55, 128.51 (dd, J = 8.9, 3.8 Hz), 127.3, 126.3, 51.7, 50.5 (d, J
= 2.1 Hz), 44.1, 40.4, 25.9; HRMS [ESI(TOF)] calcd for
C24H26NO2PCl [M + H+] 426.1390; found 426.1388.
N-(3-Cyclopropyl-3-oxo-1-phenylpropyl)-P,P-diphenylphosphinic
Amide, 2h: White solid, mp 174−176 °C, 163 mg (prepared from 0.59
1
mmol amine), 71% yield; H NMR (600 MHz, CDCl3) δ 7.83 (m,
2H), 7.78 (m, 2H), 7.46 (m, 1H), 7.40 (m, 3H), 7.32 (m, 2H), 7.27
(m, 4H), 7.20 (m, 1H), 4.60 (m, 1H), 4.45 (s, 1H), 3.30 (d, 2H, J =
5.4 Hz), 1.76 (m, 1H), 0.89 (m, 1H), 0.76 (m, 3H); 13C{1H} NMR
(150 MHz, CDCl3) δ 209.6, 142.5 (d, J = 6.9 Hz), 132.4 (d, J = 9.6
Hz), 131.8 (dd, J = 7.5, 2.7 Hz), 131.6 (d, J = 9.5 Hz), 128.5 (d, J = 11
Hz), 128.4, 127.1, 126.4, 51.8, 50.7 (d, J = 2.1 Hz), 21.5, 11.0; HRMS
[ESI(TOF)] calcd for C24H25NO2P [M + H+] 390.1623; found
390.1623 (identical to the calcd).
N-(3-Cyclopentyl-3-oxo-1-phenylpropyl)-P,P-diphenylphosphinic
ASSOCIATED CONTENT
Amide, 2i: White solid, mp 174−177 °C, 114 mg (prepared from
■
1
0.549 mmol amine), 50% yield; H NMR (600 MHz, CDCl3) δ 7.84
S
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.joc.6b01111.
(m, 2H), 7.78 (m, 2H), 7.47 (m, 1H), 7.41 (m, 3H), 7.33 (m, 2H),
7.27 (d, 4H, J = 4.2 Hz), 7.20 (m, 1H), 4.59 (m, 2H), 3.18 (m, 2H),
2.66 (m, 1H), 1.51 (m, 8H); 13C{1H} NMR (150 MHz, CDCl3) δ
212.3, 142.5 (d, J = 7.2 Hz), 132.5 (d, J = 9.6 Hz), 131.8 (dd, J = 6.6,
2.6 Hz), 131.6 (d, J = 9.5 Hz), 128.5 (dd, J = 12.5, 9.3 Hz), 128.4,
127.1, 126.3, 52.1, 51.9, 49.1, 28.1 (d, J = 17.4 Hz), 25.8 (d, J = 11.7
Hz); HRMS [ESI(TOF)] calcd for C26H29NO2P [M + H+] 418.1936;
found 418.1937.
NMR spectra and HPLC plots of the compounds and
details of the 18O labeling experiment (PDF)
AUTHOR INFORMATION
■
N-(3-Cyclohexyl-3-oxo-1-phenylpropyl)-P,P-diphenylphosphinic
Amide, 2j: White solid, mp 159−162 °C, 141 mg (prepared from
Corresponding Author
*E-mail: lp6n@virginia.edu.
1
0.617 mmol amine), 53% yield; H NMR (600 MHz, CDCl3) δ 7.83
(m, 2H), 7.78 (m, 2H), 7.46 (m, 1H), 7.41 (m, 3H), 7.32 (m, 2H),
7.26 (d, 4H, J = 4.8 Hz), 7.19 (m, 1H), 4.56 (m, 2H), 3.18 (m, 2H),
2.10 (m, 1H), 1.65 (m, 3H), 1.56 (m, 2H), 1.10 (m, 5H); 13C{1H}
Notes
The authors declare no competing financial interest.
F
DOI: 10.1021/acs.joc.6b01111
J. Org. Chem. XXXX, XXX, XXX−XXX

The Journal of Organic Chemistry
Featured Article
ACKNOWLEDGMENTS
■
Partial support of this work from the donors of the Petroleum
Research Fund, administered by the American Chemical
Society, and the U.S. National Science Foundation (CHE-
1565627) is gratefully acknowledged.
REFERENCES
■
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DOI: 10.1021/acs.joc.6b01111
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