A versatile synthesis of chiral β-aminophosphines

Article abstract of DOI:10.1039/c5ob02439k

A method for the preparation of chiral β-aminophosphines having substituted P-aryl groups is described. Ring-opening of cyclic sulfamidates with metal diarylphosphinites yields β-aminophosphine oxides, which are then reduced to the corresponding phosphines. Effects of the diarylphosphinite countercation on the regioselectivity of the ring-opening reaction (P- versus O-alkylation) are discussed. This method enables the introduction of electron-deficient, electron-rich and sterically hindered diarylphosphino groups, as demonstrated by the synthesis of a series of novel, P-aryl-substituted β-aminophosphines derived from tert-leucinol, valinol and phenylglycinol. Access to these derivatives will create new opportunities for steric and electronic tuning of β-aminophosphine-derived chiral ligands and organocatalysts.

Full text of DOI:10.1039/c5ob02439k

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A versatile synthesis of chiral β-aminophosphines†
Hsin Y. Su, Yixiong Song and Mark S. Taylor*
Cite this: DOI: 10.1039/c5ob02439k
A method for the preparation of chiral β-aminophosphines having substituted P-aryl groups is described.
Ring-opening of cyclic sulfamidates with metal diarylphosphinites yields β-aminophosphine oxides,
which are then reduced to the corresponding phosphines. Effects of the diarylphosphinite countercation
on the regioselectivity of the ring-opening reaction (P- versus O-alkylation) are discussed. This method
enables the introduction of electron-deficient, electron-rich and sterically hindered diarylphosphino
groups, as demonstrated by the synthesis of a series of novel, P-aryl-substituted β-aminophosphines
derived from tert-leucinol, valinol and phenylglycinol. Access to these derivatives will create new oppor-
tunities for steric and electronic tuning of β-aminophosphine-derived chiral ligands and organocatalysts.
Received 27th November 2015,
Accepted 18th December 2015
DOI: 10.1039/c5ob02439k
www.rsc.org/obc
on the enantioselectivity of the derived catalysts. In contrast,
modification of the phosphorus-bearing substituents R2 has
Introduction
Enantioenriched β-aminophosphines are versatile building largely been ignored in catalyst structure–activity relationships,
blocks that have been employed in modular syntheses of chiral despite the significant electronic and steric effects that could
ligands and organocatalysts. Transition metal complexes of be anticipated. Herein, we describe a protocol for the synthesis
chiral β-aminophosphine-based ligands are useful for enantio- of chiral, amino acid-derived β-aminophosphines that is com-
selective cross-couplings,1 hydrosilylations,2 hydrogenations,3 patible with the introduction of a range of phosphorus substi-
allylic substitutions4 and conjugate additions,5,6 while bifunc- tuents R2. The scope of this protocol is demonstrated through
tional, β-aminophosphine-derived organocatalysts have been the preparation of several novel derivatives having electron-
applied in enantioselective aldol,7 Morita–Baylis–Hillman8 and deficient, electron-rich and sterically hindered diarylphos-
related reactions.9,10 An advantage of β-aminophosphines in phino groups.
these applications is their straightforward synthesis from
readily available, chiral β-aminoalcohols, including those
derived from amino acids. This enables variation of the substi-
tuent R1 on the amine-bearing chirality center (Scheme 1,
eqn (1)), the identity of which often has a significant influence
Results and discussion
Several approaches to the synthesis of enantioenriched
β-aminophosphine derivatives have been explored, including sub-
stitution and aziridine ring-opening reactions using phosphorus-
centered nucleophiles,1,4,11,12 reductions of phosphonium-substi-
tuted enamines13 and conjugate additions of amines to phos-
phorus-substituted alkenes.14 For the class of β-aminoalcohol-
derived phosphines shown in Scheme 1, the most commonly
employed synthetic method involves the ring-opening of a cyclic
sulfamidate by a metal phosphide (eqn (2)).15
The preparation of derivatives having substituted diarylphos-
phino groups has not been reported, and we encountered
challenges in our attempts to make this extension. Whereas
potassium diphenylphosphide is commercially available,
accessing substituted diarylphosphides is less straightforward,
as it generally requires the synthesis and handling of air-sensi-
tive secondary diarylphosphines. For example, we prepared
potassium bis(4-(trifluoromethyl)phenyl)phosphide by a three-
step route consisting of: (i) synthesis of the corresponding sec-
ondary phosphine oxide 1a; (ii) reduction of the phosphine
Scheme 1 Approaches to the synthesis of chiral β-aminophosphines.
Department of Chemistry, University of Toronto, Toronto, ON M5S 3H6, Canada.
E-mail: mtaylor@chem.utoronto.ca
†Electronic supplementary information (ESI) available: Copies of 1H, 13C and
31P NMR spectra of all new compounds. See DOI: 10.1039/c5ob02439k
This journal is © The Royal Society of Chemistry 2015
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(S)-2a in degassed THF under argon, followed by trifluoroacetic
acid in dichloromethane to remove the Boc group (Scheme 3).
The chiral β-aminophosphine oxide product 4a was generated
in 56% isolated yield over the two steps, after purification by
flash chromatography on silica gel. Reduction of 4a to the
corresponding phosphine 3a was accomplished in 94% yield
by heating to 140 °C in diphenylsilane.19
While extending this protocol to the synthesis of other sub-
stituted derivatives, we observed the formation of an O-alkyl-
ated regioisomer from certain secondary diarylphosphine
oxide/sulfamidate combinations (Scheme 4). In particular, a
significant amount of phosphinate side product was observed
when di-ortho-tolyl-substituted 1c was used as the pro-nucleo-
phile (eqn (1)). Presumably, the bulky aryl substituents hin-
dered the desired P-alkylation reaction to the extent that
O-alkylation became competitive, with oxidation to the phos-
phinate taking place upon workup. Using NaOt-Bu in place of
KOt-Bu for this coupling provided inferior selectivity for
P- versus O-alkylation, as judged by analysis of the unpurified
reaction mixtures by 31P NMR spectroscopy. However, the
opposite trend – NaOt-Bu giving a higher preference for
P-alkylation than KOt-Bu – was observed in the coupling of 1a
with valinol-derived sulfamidate (S)-2b (eqn (2)). In any event,
case-by-case optimization of the metal counterion enabled us
to accomplish ring-opening reactions of sulfamidates 2a–2c
using diarylphosphinites bearing electron-rich, electron-
deficient and sterically hindered substituents (Scheme 5).
Each of the obtained phosphine oxides (4b–4h) was reduced
smoothly to the corresponding phosphine (3b–3h) using
Ph2SiH2.
Scheme 2 Attempted synthesis of a β-aminophosphine from a substi-
tuted diarylphosphine (Ar = 4-CF3C6H4).
oxide with diisobutylaluminum hydride (DIBAL-H);16 and (iii)
deprotonation of the obtained secondary phosphine with pot-
assium tert-butoxide. Subjecting this substituted phosphide to
the sulfamidate ring-opening/tert-butoxycarbonyl (Boc) clea-
vage protocol15 using tert-leucinol derivative (S)-2a led to a
complex mixture of products, as judged by 31P nuclear mag-
netic resonance (NMR) spectroscopy (Scheme 2). The observed
chemical shifts were consistent with the presence of phosphine
oxide derivatives, and a signal corresponding to the desired sub-
stituted β-aminophosphine 3a was not evident in the spectrum.
We note that we were able to obtain the unsubstituted diphenyl-
phosphino derivative smoothly according to the reported proto-
col, regardless of whether the potassium diphenylphosphide
was obtained from a commercial source or synthesized from
diphenylphosphine oxide. It thus appears that the presence of
the electron-withdrawing trifluoromethyl substituents has a
deleterious effect on this β-aminophosphine synthesis.
We reasoned that several advantages could arise from the
use of a metal diarylphosphinite, rather than a metal diaryl-
phosphide, as nucleophile in the sulfamidate ring-opening
reaction. By deferring the reduction of the phosphine oxide
until the final step of the process, such a route would mini-
mize the handling of oxidation-prone intermediates, and
would avoid the generation of the sensitive diarylphosphine
intermediate entirely.17,18 In situations where steric or elec-
tronic effects of the arylphosphine substituents resulted in a
less efficient sulfamidate ring-opening, the higher stability
towards purification (e.g., by silica gel chromatography) of the
phosphine oxides relative to the phosphines could be a deci-
sive advantage. To test this idea, we treated secondary phos-
phine oxide 1a with potassium tert-butoxide and sulfamidate
Derivatization of the amino group, which is often needed
for the preparation of chiral ligands or organocatalysts, can be
carried out prior to reduction of the phosphine oxide group.
For example, N-acylation of 4a, followed by chemoselective
reduction of the phosphine oxide group, yielded the corres-
ponding β-amidophosphines 5a and 5b (Scheme 6).
Conclusions
Ring-opening of cyclic sulfamidates with secondary phosphine
oxide-derived nucleophiles, followed by reduction of the
obtained phosphine oxide to the corresponding phosphine,
provides a useful means of access to chiral β-aminophosphines
having substituted P-aryl groups. Whether the potassium or
sodium diarylphosphinite nucleophile provides higher
Scheme 3 Synthesis of β-aminosphosphine 3a by diarylphosphinite/sulfamidate coupling (Ar = 4-CF3C6H4).
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Scheme 6 Synthesis of substituted β-amidophosphines.
P- versus O-alkylation regioselectivity depends on the phos-
phine oxide/sulfamidate combination employed, with steric
factors apparently playing a role. Eight novel β-aminophos-
phines have been synthesized using this approach, including
derivatives having electron-deficient, electron-rich and steri-
cally hindered diarylphosphino groups. The effects of these
types of substituents on the enantioselectivity and activity of
aminophosphine-derived transition metal complexes and
organocatalysts are worthy of further study.
Scheme 4 P- versus O-alkylation of metal diarylphosphinites.
Experimental
General methods
Unless otherwise stated, all reactions and purifications were
carried out under argon atmosphere using Schlenk, vacuum
line, or glovebox techniques in dry, oxygen-free solvents. Tetra-
hydrofuran (THF), diethyl ether, dichloromethane and
hexanes were dried using a solvent purification system and
degassed through three freeze–pump–thaw cycles. Deuterated
solvents were degassed through three freeze–pump–thaw
cycles. 400 MHz and 300 MHz spectrometers were employed
1
for recording H (400 MHz and 300 MHz), 13C{1H} (100 MHz
and 75 MHz), and 31P{1H} (161 MHz and 121 MHz) NMR
spectra at ambient temperature. 31P chemical shifts are
reported in parts per million (ppm) relative to 85% H3PO4 as
1
an external reference. H chemical shifts are reported in ppm
relative to tetramethylsilane, and were measured by referen-
cing the spectra to residual protium in the solvent. With the
exception of solvents (see above), all commercially available
reagents and chemicals were used as received without purifi-
cation. High resolution mass spectroscopy experiments were
carried out using direct analysis in real time (DART). Flash
column chromatography was carried out using 35–75 µm par-
ticle size silica gel. Secondary diarylphosphine oxides 1a,17
1b,20 1c,16 1d21 and 1e,22 and cyclic sulfamidates 2a, 2b and
2c,15 were synthesized according to published protocols.
General procedure for the ring-opening of cyclic sulfamidates
with diarylphosphine oxides, followed by cleavage of the Boc
group
(S)-(2-Amino-3,3-dimethylbutyl)bis(4(trifluoromethyl)-phenyl)-
phosphine oxide (4a). To an oven-dried screw-cap reaction
tube equipped with a magnetic stirring bar was charged pot-
assium tert-butoxide (0.11 g, 1 mmol) in a nitrogen-filled glove-
Scheme 5 Synthesis of enantioenriched, substituted β-aminophos-
phines. a The phenylglycine-derived sulfamidate of R configuration was
employed, leading to the corresponding R-configured β-aminophosphine.
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3
1
box. THF (2 mL) was then added outside of the glovebox. Bis- 5.3 Hz), 35.3 (d, JCP = 12.1 Hz), 32.9 (d, JCP = 74.7 Hz), 25.7.
(4-(trifluoromethyl)phenyl)phosphine oxide (0.34 g, 1 mmol) 31P NMR (160 MHz, CDCl3): δ 29.55. 19F NMR (376 MHz,
was dissolved in THF (2 mL) in a separate oven-dried pear- CDCl3): δ −62.95, −62.97. IR (neat, cm−1): 1360 (m), 1278 (s),
shaped flask and transferred dropwise into the reaction 1183 (s), 1170 (s), 1124 (s), 915 (m), 843 (m), 707 (m), 681 (s).
20
mixture via a syringe. The reaction was stirred at 23 °C for Optical rotation: [α]
= +9.4 (c = 0.09 g mL−1, CHCl3). HRMS
589
10 min. Cyclic sulfamidate 2a (0.28 g, 1 mmol) was dissolved (DART, m/z): calculated for C22H21F12NOP [(M + H)+]: 574.1163.
in THF (2 mL) in another oven-dried pear-shaped flask and Found: 574.1164.
transferred dropwise into the reaction mixture via a syringe.
(S)-(2-Amino-3,3-dimethylbutyl)di-o-tolylphosphine
oxide
The reaction tube was then sealed and stirred at 60 °C for (4c). Synthesized according to the general procedure using di-
18 h. The reaction was quenched with 2 N H2SO4 (25 mL) and o-tolylphosphine oxide (1c) and tert-butyl (S)-4-(tert-butyl)-
stirred vigorously at 23 °C for 45 min. It was then extracted two 1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (2a). The inter-
times with diethyl ether, and the combined organic extracts mediate treated with trifluoroacetic acid and the crude
were washed with saturated Na2CO3, followed by brine. The product was purified by flash chromatography on silica gel
solution was dried over anhydrous Na2SO4, filtered and con- (3–10% MeOH/CH2Cl2) to give the product as a colorless oil in
centrated in vacuo to give the crude product, which was used 58% yield over two steps. 1H NMR (400 MHz, CDCl3): δ 7.85
in the next step without further purification.
(ddd, J = 12.5, 7.7, 1.5 Hz, 1H), 7.63 (ddd, J = 12.8, 7.7, 1.4 Hz,
The crude product was taken up in CH2Cl2 (10 mL) and 1H), 7.45–7.36 (m, 2H), 7.35–7.29 (m, 1H), 7.29–7.23 (m, 1H),
cooled to 0 °C. Trifluoroacetic acid (2 mL, 26 mmol) was then 7.19 (dd, J = 7.5, 4.1 Hz, 2H), 2.93 (ddd, J = 12.1, 10.6, 1.2 Hz,
added dropwise. The reaction mixture was stirred at 23 °C over- 1H), 2.50 (ddd, J = 14.8, 8.6, 1.2 Hz, 1H), 2.34 (s, 3H), 2.31–2.21
night. The volatiles were then removed on the rotary evapor- (m, 1H), 2.24 (s, 3H), 0.87 (s, 9H). 13C NMR (100 MHz, CDCl3):
ator the next day. The residue was taken up in diethyl ether δ 141.9 (d, J = 8.1 Hz), 141.3 (d, J = 8.7 Hz), 132.9, 132.7 (d, J =
and washed with saturated Na2CO3. The aqueous layer was 9.4 Hz), 132.1–131.9 (m), 132.0 (d, J = 2.7 Hz), 131.3 (d, J =
2
3
separated and extracted with diethyl ether. The organic 11.2 Hz), 130.3, 55.6 (d, JCP = 4.1 Hz), 35.0 (d, JCP = 12.1 Hz),
1
extracts were then combined, washed with brine, dried over 31.0 (d, JCP = 71.7 Hz), 25.9, 21.4 (d, J = 3.9 Hz), 21.3 (d, J =
anhydrous Na2SO4, filtered and concentrated in vacuo to give 4.4 Hz). 31P NMR (160 MHz, CDCl3): δ 35.59. IR (neat, cm−1):
the crude product. Purification by flash chromatography on 2959 (s), 1593 (m), 1395 (s), 1365 (m), 1174 (s), 1138 (s),
20
silica gel (2–4% MeOH/CH2Cl2) gave the product (0.24 g, 56%) 1086 (w), 1071 (w), 754 (s), 741 (s). Optical rotation: [α]
=
589
as an off-white solid. H NMR (400 MHz, CDCl3): δ 7.90 (ddd, +49.7 (c = 0.15 g mL−1, CHCl3). HRMS (DART, m/z): calculated
1
J = 15.1, 11.0, 8.1 Hz, 4H), 7.75 (ddd, J = 16.9, 8.3, 2.4 Hz, 4H), for C20H29NOP [(M + H)+]: 330.1981. Found: 330.1981.
2.93 (ddd, J = 12.2, 11.0, 1.6 Hz, 1H), 2.50 (ddd, J = 15.0, 9.4,
(S)-(2-Amino-3,3-dimethylbutyl)bis(2-methoxyphenyl)-phos-
1.6 Hz, 1H), 2.22 (ddd, J = 15.0, 12.8, 11.0 Hz, 1H), 0.88 (s, 9H). phine oxide (4d). Synthesized according to the general pro-
1
13C NMR (125 MHz, CDCl3): δ 138.1 (d, JCP = 97.5 Hz), 136.5 cedure using bis(2-methoxyphenyl)phosphine oxide (1d), tert-
1
2
4
(d, JCP = 95.0 Hz), 134.1 (qd, JCF = 32.5 Hz, JCP = 2.5 Hz), butyl (S)-4-(tert-butyl)-1,2,3-oxathiazolidine-3-carboxylate 2,2-
134.0 (qd, 2JCF = 32.5 Hz, 4JCP = 2.5 Hz), 131.6 (d, 2JCP = 8.8 Hz), dioxide (2a) and sodium tert-butoxide. The intermediate was
131.1 (d, 2JCP = 10.0 Hz), 136.0–125.7 (m), 123.6 (q, 1JCF = 271.3 treated with trifluoroacetic acid and the crude product was
2
3
Hz), 55.7 (d, JCP = 5.0 Hz), 35.1 (d, JCP = 11.3 Hz), 32.3 (d, purified by flash chromatography on silica gel (3–10% MeOH/
1JCP = 72.9 Hz), 25.8. 31P NMR (160 MHz, CDCl3): δ 31.34. CH2Cl2) to give the product as a colorless oil in 36% yield over
IR (neat, cm−1): 1316 (s), 1183 (m), 1137 (s), 1118 (s), 1100 (s), two steps. 1H NMR (400 MHz, CDCl3): δ 7.92 (ddd, J = 12.9,
1060 (s), 1017 (s), 840 (m), 706 (s), 696 (m). Optical rotation: 7.5, 1.8 Hz, 1H), 7.57–7.48 (m, 1H), 7.46–7.36 (m, 1H), 7.26
20
[α]
= +20.5 (c = 0.12 g mL−1, CHCl3). HRMS (DART, m/z): (ddd, J = 14.0, 7.6, 2.0 Hz 1H), 7.14–7.07 (m, 1H), 6.94–6.85 (m,
589
calculated for C20H23F6NOP [(M + H)+]: 438.1412. Found: 3H), 3.82 (s, 3H), 3.66 (s, 3H), 2.82–2.65 (m, 2H), 2.47 (td, J =
438.1416.
15.2, 11.1 Hz, 1H), 0.82 (s, 9H). 13C NMR (100 MHz, CDCl3):
4
4
(S)-(2-Amino-3,3-dimethylbutyl)bis(3,5-bis(trifluoromethyl)- δ 161.3 (d, JCP = 3.0 Hz), 159.8 (d, JCP = 3.8 Hz), 135.5 (d, J =
phenyl)phosphine oxide (4b). Synthesized according to the 5.6 Hz), 133.9 (d, J = 2 Hz), 133.5 (d, J = 2.1 Hz), 121.7 (d, J =
general procedure using bis(3,5-bis(trifluoromethyl)-phenyl)- 100.8 Hz), 121.1 (d, J = 10.9 Hz), 120.5 (d, J = 11.9 Hz), 119.3
phosphine oxide (1b) and tert-butyl (S)-4-(tert-butyl)-1,2,3- (d, J = 98.4 Hz), 56.3 (d, 2JCP = 5.0 Hz), 55.8, 55.3, 34.7 (d, 3JCP
=
oxathiazolidine-3-carboxylate 2,2-dioxide (2a). The intermedi- 13.4 Hz), 31.3 (d, JCP = 74.1 Hz), 25.9. 31P NMR (160 MHz,
1
ate was treated with trifluoroacetic acid and the crude product CDCl3): δ 35.18. IR (neat, cm−1): 2958 (m), 1590 (s), 1576 (m),
was purified by flash chromatography on silica gel (1–2% 1478 (s), 1432 (s), 1277 (s), 1246 (s), 1163 (s), 1137 (s), 1073
20
MeOH/CH2Cl2) to give the product as a white solid in 21% (m), 1020 (m), 801 (m), 758 (s). Optical rotation: [α]
= +38.2
589
yield over two steps. H NMR (400 MHz, CDCl3): δ 8.24 (t, J = (c = 0.11 g mL−1, CHCl3). HRMS (DART, m/z): calculated for
11.2 Hz, 4H), 8.06 (d, J = 17.6 Hz, 2H), 2.96 (ddd, J = 12.4, 11.0, C20H29NO3P [(M + H)+]: 362.1889. Found: 362.1885.
1
1.8 Hz, 1H), 2.55 (ddd, J = 15.2, 10.7, 1.8 Hz, 1H), 2.28 (dt, J =
(S)-(2-Amino-3-methylbutyl)bis(4-(trifluoromethyl)phenyl)-
15.1, 11.3 Hz, 1H), 0.91 (s, 9H). 13C NMR (100 MHz, CDCl3): phosphine oxide (4e). Synthesized according to the general
1
1
δ 136.8 (d, JCP = 97.3 Hz), 135.8 (d, JCP = 95.2 Hz), 132.7 (m), procedure using bis(4-(trifluoromethyl)phenyl)phosphine
2
130.9 (m), 126.2 (m), 122.8 (q, J = 272.0 Hz), 55.9 (d, JCP
=
oxide (1a) and tert-butyl (S)-4-isopropyl-1,2,3-oxathiazolidine-
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1
3-carboxylate 2,2-dioxide (2b). The intermediate was purified J = 4.3 Hz), 34.4 (d, J = 12.7 Hz), 33.9 (d, JCP = 72.8 Hz), 18.2,
by flash chromatography on silica gel (20% EtOAc/CH2Cl2) 17.7. 31P NMR (160 MHz, CDCl3): δ 33.14. IR (neat, cm−1):
before treatment with trifluoroacetic acid. Product was 2956 (m), 2839 (w), 1596 (s), 1570 (m), 1503 (s), 1463 (m), 1408
obtained in 65% yield over two steps as a colorless oil. 1H (m), 1292 (s), 1253 (s), 1173 (s), 1119 (s), 1026 (s), 930 (m), 829
20
NMR (300 MHz, CDCl3): δ 7.98–7.82 (m, 4H), 7.79–7.68 (m, (s), 802 (s), 762 (m), 729 (m), 660 (m). Optical rotation: [α]
=
589
4H), 3.07 (m, 1H), 2.67–2.18 (m, 2H), 1.91 (s, 2H), 1.67 (m, +36.1 (c = 0.12 g mL−1, CHCl3). HRMS (DART, m/z): calculated
1H), 0.88 (app dd, J = 6.8, 5.6 Hz, 6H). 13C NMR (75 MHz, for C19H27NO3P [(M + H)+]: 348.1729. Found 348.1733.
1
1
CDCl3): δ 137.7 (d, JCP = 95.4 Hz), 136.5 (d, JCP = 96.3 Hz),
(R)-(2-Amino-2-phenylethyl)bis(4-(trifluoromethyl)phenyl)-
134.5–134.0 (m), 134.0–133.6 (m), 131.4 (d, J = 9.5 Hz), 131.0 phosphine oxide (4h). Synthesized according to the general
3
(d, J = 9.8 Hz), 126.3–125.5 (m), 124.8, 122.1, 52.0 (d, JCP
=
procedure using bis(4-(trifluoromethyl)phenyl)phosphine
2
1
4.6 Hz), 34.7 (d, JCP = 12.7 Hz), 33.8 (d, JCP = 72.9 Hz), 18.3, oxide (1a) and tert-butyl (R)-4-phenyl-1,2,3-oxathiazolidine-3-
17.5. 31P NMR (120 MHz, CDCl3): δ 30.79. IR (neat, cm−1): carboxylate 2,2-dioxide (1c). The intermediate was purified by
3044 (w), 2961 (w), 1684 (w), 1400 (m), 1317 (s), 1183 (m), 1163 flash chromatography on silica gel (10% EtOAc/CH2Cl2) before
(s), 1117 (s), 1100 (s), 1060 (s), 1017 (s), 840 (m), 790 (m), 764 treatment with trifluoroacetic acid. Product was obtained in
20
589
1
(m), 708 (s), 670 (m). Optical rotation: [α] = +26.8 (c = 0.08 g 35% yield over two steps as a white solid. H NMR (300 MHz,
mL−1, CHCl3). HRMS (DART, m/z): calculated for C19H21F6NOP CDCl3): δ 7.93–7.77 (m, 4H), 7.77–7.65 (m, 4H), 7.39–7.11 (m,
[(M + H)+]: 424.1265. Found 424.1267.
5H), 4.51 (ddd, J = 10.5, 9.0, 4.0 Hz, 1H), 2.90–2.60 (m, 2H),
(S)-(2-Amino-3-methylbutyl)di-o-tolylphosphine oxide (4f). 1.94 (s, 2H). 13C NMR (75 MHz, CDCl3): δ 145.0 (s), 144.9 (s),
Synthesized according to the general procedure using di- 131.3 (d), 130.9 (d), 128.8, 127.8, 126.1, 125.7 (dt, J = 11.9,
o-tolylphosphine oxide (1c), tert-butyl (S)-4-isopropyl-1,2,3- 3.8 Hz), 51.3 (d, J = 3.4 Hz), 39.5 (d, JCP = 69.9 Hz). 31P NMR
1
oxathiazolidine-3-carboxylate 2,2-dioxide (2b) and sodium tert- (120 MHz, CDCl3): δ 28.52. IR (neat, cm−1): 2900 (w), 1496 (w),
butoxide. The intermediate was purified by flash chromato- 1456 (w), 1400 (m), 1321 (s), 1165 (s), 1120 (s), 1100 (s), 1061
graphy on silica gel (25% EtOAc/CH2Cl2) before treatment with (s), 1017 (s), 835 (m), 789 (m), 768 (m), 742 (m), 708 (m), 696
20
trifluoroacetic acid. Product was obtained in 45% yield over (s). Optical rotation: [α]
= –18.7 (c = 0.10 g mL−1, CHCl3).
589
two steps as a colorless oil. H NMR (400 MHz, CDCl3): δ 7.81 HRMS (DART, m/z): calculated for C22H19F6NOP [(M + H)+]:
(ddd, J = 12.5, 7.7, 1.5 Hz, 1H), 7.64 (ddd, J = 12.9, 7.7, 1.4 Hz, 458.1108. Found 458.1109.
1H), 7.46–7.34 (m, 2H), 7.34–7.24 (m, 2H), 7.24–7.12 (m, 2H),
1
General procedure for reduction of β-aminophosphine oxides
3.21–2.89 (m, 1H), 2.49–2.45 (m, 2H), 2.46–2.34 (m, 2H), 2.31
(s, 3H), 2.22 (s, 3H), 1.79–1.61 (m, 1H), 0.87 (app t, 6H).
(S)-1-(Bis(4-(trifluoromethyl)phenyl)-phosphanyl)-3,3-di-
13C NMR (100 MHz, CDCl3): δ 141.7 (d, J = 8.4 Hz), 141.2 (d, J = methylbutan-2-amine (3a). To a 0.5-dram vial equipped with
8.8 Hz), 132.4 (d, J = 9.6 Hz), 132.0 (d, J = 96.4 Hz), 132.0, a magnetic stirring bar was added (S)-(2-amino-3,3-dimethyl-
1
131.9, 131.9, 131.9, 131.3 (d, J = 11.1 Hz), 130.7 (d, JCP
=
butyl)bis(4-(trifluoromethyl)phenyl)phosphine oxide (3a, 0.3 g,
95.3 Hz), 125.8 (d, J = 6.6 Hz), 125.7 (d, J = 7.0 Hz), 52.2 (d, J = 0.68 mmol). Ph2SiH2 (0.89 mL, 4.78 mmol) was added and the
1
4.0 Hz), 34.5 (d, J = 12.8 Hz), 32.4 (d, JCP = 71.9 Hz), 21.3 (d, vial was sealed. Allowed reaction to stir vigorously at 140 °C for
J = 4.0 Hz), 21.2 (d, J = 4.4 Hz), 18.2, 17.9. 31P NMR (160 MHz, 20 h. The product was then purified by flash chromatography
CDCl3): δ 35.29. IR (neat, cm−1): 2957 (m), 2871 (w), 1593 (m), on silica gel using a positive pressure of N2 and solvents pre-
1568 (m), 1452 (s), 1385 (m), 1283 (m), 1174 (s), 1138 (s), 1084 sparged with N2 (2.0–3.5% MeOH/CH2Cl2) to give the product
(w), 1071 (w), 927 (m), 805 (m), 751 (s), 730 (s), 688 (m). (0.27 g, 94%) as a yellow oil. 1H NMR (400 MHz, CDCl3):
Optical rotation: [α]25809 = +68.7 (c = 0.19 g mL−1, CHCl3). HRMS δ 7.68–7.61 (m, 4H), 7.52–7.43 (m, 4H), 2.62–2.59 (m, 1H),
(DART, m/z): calculated for C19H27F6NOP [(M + H)+]: 316.1830. 2.46–2.42 (m, 2H), 0.94 (s, 9H). 13C NMR (100 MHz, CDCl3):
1
2
Found 316.1834.
δ 141.2 (d, JCP = 16.7 Hz), 134.7 (d, JCP = 20.4 Hz), 132.3 (d,
2
(S)-(2-Amino-3-methylbutyl)bis(4-methoxyphenyl)-phosphine J = 16.9 Hz), 130.6 (d, JCF = 32.4 Hz), 125.5 (m), 125.3 (m),
1
2
oxide (4g). Synthesized according to the general procedure 124.0 (q, JCF = 257.3 Hz), 58.6 (d, JCP = 13.2 Hz), 34.8 (d,
using bis(4-methoxyphenyl)phosphine oxide (1e), tert-butyl 3JCP = 5.5 Hz), 30.6 (d, JCP = 15.7 Hz), 26.2. 31P NMR
1
(S)-4-isopropyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (160 MHz, CDCl3): δ −29.92. 19F NMR (376 MHz, CDCl3):
(2b) and sodium tert-butoxide. The intermediate was purified δ −62.95, −63.04. IR (neat, cm−1): 1607 (w), 1323 (s), 1166 (m),
by flash chromatography on silica gel (2% MeOH/CH2Cl2) 1125 (s), 1061 (s), 1016 (m), 831 (w), 699 (w). Optical rotation:
before treatment with trifluoroacetic acid. Product was [α]25809 = +20.1 (c = 0.14 g mL−1, CHCl3). HRMS (DART, m/z): calcu-
obtained in 35% yield over two steps as a colorless oil. 1H lated for C20H23F6NP [(M + H)+]: 422.1469. Found: 438.1472.
NMR (400 MHz, CDCl3): δ 7.69–7.54 (m, 4H), 6.93 (m, 4H),
(S)-1-(Bis(3,5-bis(rifluoromethyl)phenyl)phosphanyl)-3,3-di-
3.80 (s, 3H), 3.77 (s, 3H), 3.00 (dddd, J = 11.7, 9.6, 4.9, 2.6 Hz, methylbutan-2-amine (3b). Synthesized according to the
1H), 2.69 (s, 3H), 2.36–2.09 (m, 2H), 1.65 (pd, J = 6.8, 4.8 Hz, general procedure using (S)-(2-amino-3,3-dimethylbutyl)-bis-
1H), 0.83 (app t, J = 6.7 Hz, 6H). 13C NMR (100 MHz, CDCl3): (3,5-bis(trifluoromethyl)phenyl)phosphine oxide (4b). The
δ 162.3 (d, J = 2.8 Hz), 162.2 (d, J = 2.9 Hz), 132.7 (d, J = 10.5 crude product was purified by flash chromatography on silica
1
Hz), 132.3 (d, J = 10.8 Hz), 125.4 (d, JCP = 105.3 Hz), 123.4 (d, gel (0.3–0.5% MeOH/CH2Cl2) to give the product in 56% yield
J = 104.8 Hz), 55.3 (d, J = 1.6 Hz), 55.3 (d, J = 1.7 Hz), 52.0 (d, as a yellow oil. 1H NMR (400 MHz, CDCl3): δ 7.93 (m, 3H),
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7.85–7.76 (m, 3H), 2.53–2.37 (m, 2H), 1.94 (ddd, J = 13.6, 11.8, purified by flash chromatography on silica gel (2% MeOH/
1
5.2 Hz, 1H), 0.90 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 142.6 CH2Cl2) to give the product in 53% yield as a colorless oil. H
1
2
(d, JCP = 20.0 Hz), 140.5 (d, JCP = 21.4 Hz), 133.5 (m), NMR (300 MHz, CDCl3): δ 7.78–7.41 (m, 8H), 2.63 (m, 1H),
1
132.9–131.6 (m), 123.8 (quint, J = 3.8 Hz), 123.2 (qd, JCF
271.0 Hz, 4JCP = 3.1 Hz), 122.9 (quint. J = 3.7 Hz), 58.5 (d, 2JCP
=
=
2.33 (m, 1H), 2.04 (m, 1H), 1.72 (m, 1H), 0.90 (app dd, J = 7.9,
6.8 Hz, 6H). 13C NMR (75 MHz, CDCl3): δ 143.8 (d, J = 15.5 Hz),
3
1
11.8 Hz), 35.4 (d, JCP = 6.2 Hz), 32.4 (d, JCP = 11.3 Hz), 25.8. 142.6 (d, J = 16.8 Hz), 133.5 (d, J = 19.8 Hz), 132.6 (d, J =
31P NMR (160 MHz, CDCl3): δ −15.68. 19F NMR (376 MHz, 18.4 Hz), 131.2 (d, J = 32.4 Hz), 130.7 (d, J = 32.6 Hz), 125.9
CDCl3): δ −63.06. IR (neat, cm−1): 1352 (s), 1274 (s), 1172 (m), −124.9 (m), 54.2 (d, J = 13.1 Hz), 34.6 (d, J = 7.4 Hz), 34.4 (d, J =
1118 (s), 1094 (s), 893 (m), 844 (m), 702 (s), 681 (s). Optical 12.3 Hz), 18.8, 17.0. 31P NMR (120 MHz, CDCl3): δ −20.39.
rotation: [α] = +33.7 (c = 0.05 g mL−1, CHCl3). HRMS (DART, IR (neat, cm−1): 1606 (w), 1396 (w), 1319 (s), 1164 (m), 1121 (s),
20
589
m/z): calculated for C22H21F12NP [(M + H)+]: 558.1221. Found: 1059 (s), 1015 (m), 829 (m), 710 (w), 697 (m). Optical rotation:
558.1220.
(S)-1-(Di-o-tolylphosphanyl)-3,3-dimethylbutan-2-amine (3c). culated for C19H21F6NP [(M + H)+]: 408.1316. Found 408.1315.
Synthesized according to the general procedure using (S)-(2- (S)-1-(Di-o-tolylphosphanyl)-3-methylbutan-2-amine (3f).
[α]25089 = +23.2 (c = 0.13 g mL−1, CHCl3). HRMS (DART, m/z): cal-
amino-3,3-dimethylbutyl)di-o-tolylphosphine oxide (4c). The Synthesized according to the general procedure using (S)-(2-
crude product was purified by flash chromatography on silica amino-3-methylbutyl)di-o-tolylphosphine oxide (4f). The crude
gel (2% MeOH/CH2Cl2) to give the product in 46% yield as a product was purified by flash chromatography on silica gel
1
yellow solid. H NMR (400 MHz, CDCl3): δ 7.24–7.12 (m, 8H), (2% MeOH/CH2Cl2) to give the product in 60% yield as a color-
2.51 (ddd, J = 11.1, 9.1, 1.8 Hz, 1H), 2.45 (s, 3H), 2.44 (s, 3H), less oil. 1H NMR (400 MHz, CDCl3): δ 7.25–7.10 (m, 8H),
2.35 (ddd, J = 13.7, 4.1, 1.8 Hz, 1H), 1.68 (ddd, J = 13.8, 11.4, 2.81–2.63 (m, 1H), 2.45 (s, 3H), 2.43 (s, 3H), 2.25 (ddd, J = 13.8,
4.9 Hz, 1H), 0.89 (s, 9H). 13C NMR (100 MHz, CDCl3): δ 143.2 4.4, 1.6 Hz, 1H), 1.94 (ddd, J = 13.8, 9.2, 2.9 Hz, 1H), 1.83 (m,
(d, J = 25.6 Hz), 142.0 (d, J = 25.3 Hz), 137.7 (d, J = 12.1 Hz), 1H), 0.95 (d, J = 6.8 Hz, 3H), 0.91 (d, J = 6.8 Hz, 3H). 13C NMR
136.2 (d, J = 13.8 Hz), 131.4 (d, J = 13.3 Hz), 130.2 (d, J = (100 MHz, CDCl3): δ 142.7 (d, J = 25.7 Hz), 142.0 (d, J = 25.6
1.7 Hz), 130.2 (d, J = 1.4 Hz), 128.6 (d, J = 24.4 Hz), 126.1 (d, J = Hz), 137.2 (d, J = 12.3 Hz), 136.4 (d, J = 13.4 Hz), 131.2 (d, J =
2
3
8.4 Hz), 57.8 (d, JCP = 12.8 Hz), 35.1 (d, JCP = 6.2 Hz), 31.2 (d, 7.7 Hz), 130.1 (d, J = 2.2 Hz), 130.1 (d, J = 2.0 Hz), 128.4 (d, J =
1JCP = 10.9 Hz), 26.1, 21.6 (d, J = 11.2 Hz), 21.4 (d, J = 10.6 Hz). 11.7 Hz), 126.1 (d, J = 0.8 Hz), 126.0 (d, J = 0.8 Hz), 54.0 (d, J =
31P NMR (160 MHz, CDCl3): δ −42.08. IR (neat, cm−1): 2956 14.0 Hz), 34.3 (d, J = 7.4 Hz), 33.4 (d, J = 12.1 Hz), 21.4 (d, J =
(s), 1469 (s), 1452 (s), 1363 (m), 1272 (w), 1200 (w), 1130 (s), 7.7 Hz), 21.2 (d, J = 7.4 Hz), 19.0, 17.0. 31P NMR (160 MHz,
1068 (w), 1031 (w), 839 (w), 804 (w), 746 (s), 719 (s). Optical CDCl3): δ −44.02. IR (neat, cm−1): 3055 (w), 2956 (m), 1589 (w),
20
rotation: [α] = +86.1 (c = 0.05 g mL−1, CHCl3). HRMS (DART, 1466 (m), 1451 (m), 1378 (m), 1270 (w), 1200 (w), 1130 (m),
589
m/z): calculated for C20H29NP [(M + H)+]: 314.2034. Found: 1032 (m), 910 (w), 747 (s), 719 (m). Optical rotation: [α]
=
20
589
314.2038.
(S)-1-(Bis(2-methoxyphenyl)phosphanyl)-3,3-dimethylbutan-2- for C19H27NP [(M + H)+]: 300.1881. Found 300.1889.
amine (3d). Synthesized according to the general procedure (S)-1-(Bis(4-methoxyphenyl)phosphanyl)-3-methylbutan-2-
+82.4 (c = 0.10 g mL−1, CHCl3). HRMS (DART, m/z): calculated
using (S)-(2-amino-3,3-dimethylbutyl)di-o-tolylphosphine oxide amine (3g). Synthesized according to the general procedure
(4d). The crude product was purified by flash chromatography using (S)-(2-amino-3-methylbutyl)bis(4-methoxyphenyl)-phos-
on silica gel (3–10% MeOH/CH2Cl2) to give the product in 51% phine oxide (4g). The crude product was purified by flash
yield as a colorless oil. 1H NMR (400 MHz, CDCl3): δ 7.36 (ddd, chromatography on silica gel (3% MeOH/CH2Cl2) to give the
J = 8.2, 7.4, 1.7 Hz, 1H), 7.33–7.23 (m, 2H), 7.05 (ddd, J = 7.3, product in 40% yield as a colorless oil. 1H NMR (300 MHz,
5.2, 1.7 Hz, 1H), 6.95 (td, J = 7.4, 1.0 Hz, 1H), 6.91–6.82 (m, CDCl3): δ 7.44–7.31 (m, 4H), 6.93–6.80 (m, 4H), 3.80 (s, 3H),
3H), 3.82 (s, 3H), 3.78 (s, 3H), 2.59 (ddd, J = 11.6, 9.2, 2.0 Hz, 3.78 (s, 3H), 2.66 (m, 1H), 2.25 (m, 1H), 1.99 (m, 1H), 1.75 (m,
1H), 2.53–2.46 (ddd, J = 13.6, 4.8, 2.0 Hz, 1H), 1.87 (ddd, J = 1H), 1.26 (br s, 2H), 0.91 (d, J = 9.1 Hz, 3H), 0.88 (d, J = 9.0 Hz,
14.0, 12.0, 3.6 Hz, 1H), 0.92 (s, 9H). 13C NMR (100 MHz, 3H). 13C NMR (75 MHz, CDCl3): δ 160.3, 159.9, 134.5 (d, J =
CDCl3): δ 134.4, 133.7 (d, J = 9.2 Hz), 132.7 (d, J = 4.4 Hz), 20.6 Hz), 133.8 (d, J = 19.5 Hz), 130.2 (d, J = 9.3 Hz), 129.1 (d,
130.6, 130.0, 121.0 (d, J = 16.7 Hz), 110.5 (d, J = 15.4 Hz), 58.6, J = 10.4 Hz), 114.2 (d, J = 4.7 Hz), 114.1 (d, J = 4.1 Hz), 55.2,
2
3
58.4, 55.7 (d, JCP = 10.7 Hz), 35.0 (d, JCP = 6.3 Hz), 29.1 (d, 54.2, 54.1, 35.1 (d, J = 11.1 Hz), 34.2 (d, J = 7.6 Hz), 18.9, 17.2.
1JCP = 9.8 Hz), 26.3. 31P NMR (160 MHz, CDCl3): δ −39.00. 31P NMR (120 MHz, CDCl3): δ −25.59. IR (neat, cm−1): 2956
IR (neat, cm−1): 1584 (m), 1573 (m), 1463 (s), 1430 (s), 1271 (m), 2835 (w), 1593 (s), 1568 (m), 1497 (s), 1462 (m), 1441 (m),
(m), 1239 (s), 1129 (w), 1072 (w), 1024 (s), 793 (w), 753 (s). 1401 (w), 1282 (s), 1245 (s), 1176 (s), 1094 (s), 1030 (s), 910 (w),
20
Optical rotation: [α]25809 = +38.2 (c = 0.12 g mL−1, CHCl3). HRMS 825 (s), 797 (m), 732 (m). Optical rotation: [α]
= +71.4 (c =
589
(DART, m/z): calculated for C20H29NO3P [(M + H)+]: 362.1889. 0.05 g mL−1, CHCl3). HRMS (DART, m/z): calculated for
Found: 362.1885.
C19H27NO2P [(M + H)+]: 332.1779. Found 332.1781.
(S)-1-(Bis(4-(trifluoromethyl)phenyl)phosphanyl)-3-methyl-
(R)-2-(Bis(4-(trifluoromethyl)phenyl)phosphanyl)-1-phenyl-
butan-2-amine (3e). Synthesized according to the general pro- ethan-1-amine (3h). Synthesized according to the general
cedure using (S)-(2-amino-3-methylbutyl)bis(4-(trifluoro- procedure using (R)-(2-amino-2-phenylethyl)bis(4-(trifluoro-
methyl)phenyl)phosphine oxide (4e). The crude product was methyl)phenyl)phosphine oxide (4h). The crude product was
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purified by silica gel chromatography (2% MeOH/CH2Cl2) to CH2Cl2) gave the product in 56% yield over two steps as a color-
give the product in 52% yield as a yellow oil. 1H NMR less oil. 1H NMR (400 MHz, CDCl3): δ 7.62–7.52 (m, 6H),
(300 MHz, CDCl3): δ 7.63–7.55 (m, 4H), 7.55–7.44 (m, 4H), 7.52–7.42 (m, 5H), 5.74 (d, J = 10.2 Hz, 1H), 4.20 (dddd, J = 13.1,
7.41–7.16 (m, 5H), 4.03 (m, 1H), 2.67–2.41 (m, 2H), 1.82 (s, 11.1, 8.4, 2.8 Hz, 1H), 2.52 (td, J = 13.9, 2.8 Hz, 1H), 2.17 (ddd,
2H). 13C NMR (75 MHz, CDCl3): δ 133.3 (d, J = 19.6 Hz), 132.8 J = 14.2, 12.0, 2.5 Hz, 1H), 0.97 (s, 9H). 13C NMR (100 MHz,
(d, J = 18.9 Hz), 128.7 (s), 127.5 (s), 126.1 (s), 125.3 (m), 53.9 (d, CDCl3): δ 167.0, 134.7, 133.5 (d, J = 19.3 Hz), 133.1 (d, J = 19.4
2
J = 16.5 Hz), 39.43 (d, J = 14.7 Hz). 31P NMR (120 MHz, CDCl3): Hz), 131.6, 128.7, 126.8, 125.5 (m), 55.0 (d, JCP = 14.7 Hz), 35.9
3
1
δ −21.05. IR (neat, cm−1): 2935 (w), 2870 (w), 1606 (m), 1454 (d, JCP = 6.8 Hz), 30.9 (d, JCP = 14.3 Hz), 26.4. 31P NMR
(w), 1398 (m), 1321 (s), 1165 (s), 1119 (s), 1104 (s), 1059 (s), (160 MHz, CDCl3): δ −20.19. 19F NMR (376 MHz, CDCl3):
1015 (s), 952 (m), 879 (m), 828 (s), 769 (m), 724 (m), 699 (s). δ −62.90. IR (neat, cm−1): 1641 (m), 1520 (m), 1321 (s), 1162 (s),
Optical rotation: [α]25809 = –26.0 (c = 0.07 g mL−1, CHCl3). HRMS 1120 (s), 1106 (s), 1059 (s), 830 (m), 818 (m), 691 (m). Optical
20
(DART, m/z): calculated for C22H19F6NP [(M + H)+]: 442.1153. rotation: [α] = +22.7 (c = 0.04 g mL−1, CHCl3). HRMS (DART,
589
Found 442.1159.
m/z): calculated for C27H27F6NOP [(M + H)+]: 526.1736. Found
526.1734.
General procedure for acylation and reduction of
β-aminophosphine oxides
(S)-N-(1-(Bis(4-(trifluoromethyl)phenyl)phosphanyl)-3,3-di-
methylbutan-2-yl)pivalamide (5a). To an oven-dried round-
Acknowledgements
bottom flask equipped with a magnetic stirring bar was added Acknowledgement is made to the donors of the American
(S)-(2-amino-3,3-dimethylbutyl)bis(4-(trifluoromethyl)phenyl)- Chemical Society Petroleum Research Fund for partial support
phosphine oxide (4a, 20 mg, 46 μmol). Pyridine (0.1 mL) was of this research. Funding was also provided by NSERC (Discovery
added and the reaction mixture was cooled to 0 °C. Trimethyl- Grants and Canada Research Chairs Programs) and the Canada
acetyl chloride (6 μL, 50 μmol) was added dropwise via a Foundation for Innovation (projects #17545 and 19119).
microsyringe. The reaction was stirred at room temperature
overnight. The reaction mixture was then quenched with H2O
and extracted two times with EtOAc. The combined organic
extracts were washed once with saturated NaHCO3, twice with
Notes and references
10% CuSO4, then once with brine. The solution was then dried
over anhydrous Na2SO4, filtered and concentrated in vacuo to
give the crude product. Purification by flash chromatography
on silica gel (2.5% MeOH/CH2Cl2) gave the intermediate as a
white solid.
1 T. Hayashi, M. Konishi, M. Fukushima, K. Kanehira,
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The phosphine oxide intermediate was reduced following
the general procedure for reduction of β-aminophosphine
oxides. The crude product was purified by flash chromato-
graphy on silica gel (0.2% MeOH/CH2Cl2) to afford the product
(17.6 mg, 76% over two steps) as a white solid. 1H NMR
(400 MHz, CDCl3): δ 7.60–7.58 (m, 4H), 7.56–7.44 (m, 4H), 5.46
(d, J = 10.2 Hz, 1H), 3.89 (dddd, J = 11.6, 10.2, 8.7, 2.8 Hz, 1H),
2.43 (ddd, J = 13.8, 4.4, 2.8 Hz, 1H), 1.98 (ddd, J = 13.8, 11.9,
4.5 Hz, 1H), 1.16 (s, 9H), 0.88 (s, 9H). 13C NMR (100 MHz,
CDCl3): δ 177.5, 133.8 (d, J = 19.8 Hz), 132.7 (d, J = 18.7 Hz),
2
3
125.4 (m), 53.6 (d, JCP = 13.0 Hz), 39.0, 35.6 (d, JCP = 6.3 Hz),
31.1 (d, 1JCP = 13.6 Hz), 27.7, 26.3. 31P NMR (160 MHz, CDCl3):
δ −21.03. 19F NMR (376 MHz, CDCl3): δ −62.89. IR (neat,
cm−1): 1647 (m), 1513 (m), 1320 (s), 1168 (s), 1118 (s), 1103 (s),
20
1059 (s), 838 (m), 827 (m), 696 (m). Optical rotation: [α]
=
589
+25.4 (c = 0.07 g mL−1, CHCl3). HRMS (DART, m/z): calculated
for C25H31F6NOP [(M + H)+]: 506.2044. Found 506.2047.
(S)-N-(1-(Bis(4-(trifluoromethyl)phenyl)phosphanyl)-3,3-di-
methylbutan-2-yl)benzamide (5b). Synthesized according to
the general procedure using (S)-(2-amino-3,3-dimethylbutyl)bis-
(4-(trifluoromethyl)phenyl)phosphine oxide (4a) and benzoyl
chloride. The intermediate was purified by flash chromato-
graphy on silica gel (2.5% MeOH/CH2Cl2) before treatment with
Ph2SiH2. Flash chromatography on silica gel (0.2% MeOH/
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