Highly Acidic BINOL-Derived Phosphoramidimidates and their Application in the Bronsted Acid Catalyzed Synthesis of α-Tocopherol

Article abstract of DOI:10.1055/s-0035-1560971

The design and synthesis of highly acidic BINOL-derived N,N′-bistriflylphosphoramidimidate and N,N′-bisarylsulfonylphosphoramidimidate Bronsted acid catalysts are reported.

Full text of DOI:10.1055/s-0035-1560971

SYNLETT
0
9
3
6
-
5
2
1
4
1
4
3
7
-
2
0
9
6
©
Georg Thieme Verlag Stuttgart · New York
2016, 27, 156–158
156
letter
Synlett
P. S. Kaib, B. List
Letter
Highly Acidic BINOL-Derived Phosphoramidimidates and their Ap-
plication in the Brønsted Acid Catalyzed Synthesis of α-Tocopherol
i-Pr
i-Pr
Philip S. J. Kaib
Benjamin List*
stereo-controlling group
Tf
i-Pr
Max-Planck-Institut für Kohlenforschung,
Kaiser-Wilhelm-Platz 1, 45470 Mülheim an der Ruhr,
Germany
basic site
O
O
N
C2-symmetric anion
P
NH acidic site
list@mpi-muelheim.mpg.de
i-Pr
Tf
electron-deficient and
stereo-controlling group
Dedicated to Professor Steven V. Ley on the occasion
th
of his 70 birthday
i-Pr
i-Pr
phosphoramidimidate
Received: 02.11.2015
Accepted after revision: 06.11.2015
Published online: 30.11.2015
a specific substrate.10 Herein we disclose the design and
synthesis of BINOL-derived N,N′-bistriflylphosphoramidim-
idates and N,N′-bisarylsulfonylphosphoramidimidates as a
new class of highly acidic Brønsted acid catalysts.
DOI: 10.1055/s-0035-1560971; Art ID: st-2015-d0862-l
Abstract The design and synthesis of highly acidic BINOL-derived
N,N′-bistriflylphosphoramidimidate and N,N′-bisarylsulfonylphosphora-
midimidate Brønsted acid catalysts are reported.
Key to the design of Brønsted acid catalysts that are
more acidic than the established phosphoric acids is to in-
10
crease the stability of the corresponding counteranion.
Key words N,N′-bistriflylphosphoramidimidate, N,N′-bisarylsulfonyl-
Unfortunately, systematic studies on the acidities and pKa
values of phosphoric acids and their derivatives are rela-
tively scarce. Furthermore, these investigations were typi-
cally conducted in solvents such as acetonitrile (MeCN) and
dimethyl sulfoxide (DMSO) that are generally unfavorable
for asymmetric Brønsted acid catalysis.11 Detailed studies
on the stability and acidity of Brønsted acids, in particular
benzoic acid derivatives, were reported by Yagupolskii
(Scheme 1).12 Here the replacement of an oxo group with
a stronger electron acceptor, such as the NSO CF group
phosphoramidimidate, BINOL-derived, chiral Brønsted acid, C -sym-
2
metric anions
Within the last ten years, BINOL-derived phosphoric ac-
ids 1 have become highly privileged motifs in asymmetric
Brønsted acid catalysis.1–5 In 2004, Akiyama and Terada
6
7
introduced this catalyst class, setting the road for the cur-
rent dominance of phosphoric acids in modern organoca-
13
8
talysis. Chiral Brønsted acids have since been demonstrat-
2
3
ed to be highly efficient and versatile catalysts for a contin-
uously expanding list of challenges in asymmetric
(NTf), significantly increased the stability of the counteran-
10,12
ions and the acidity of the corresponding acids.
The
1–3,5
14
synthesis.
One key reason for this success has been the
acidity increases from benzoic acid (3, pK = 20 in MeCN)
a
facile structure modulation of phosphoric acids 1 enabling
the fine tuning of electronic and steric properties.6 The
acidic functional group is located in a well-defined space,
inducing stereochemical information provided by the chiral
backbone onto the substrate placed in the catalytically ac-
to N-triflyl benzamide (4, pK = 11 in MeCN), and even fur-
a
ther to N,N′-bis-triflyl benzimidamide (5, pK = 6 in MeCN),
a
illustrating the high potential of this approach.12
This general strategy has also been exploited in phos-
phoramides 2.10 However, in their deprotonated form, acids
1,3
tive pocket. Furthermore, the utility in diverse reactions
is achieved by manifold activation modes, including bifunc-
tional activation, in addition to pure Brønsted acidity.1–3,5,9
Yet Brønsted acids 1 activate only a limited number of rela-
2 lack the superior C -symmetry of BINOL phosphates, po-
2
tentially limiting their general applicability.15 We therefore
felt that even more acidic and symmetric chiral Brønsted
acids such as bissulfonylphosphoramidimidates 6 that, as
1–3,5
13
tively basic functional groups, typically imines.
The de-
compared to acids 2, also feature one additional electron-
velopment of more acidic chiral acids is crucial towards ex-
panding the applicability of asymmetric Brønsted acid ca-
talysis towards less basic substrates, such as ketones,
aldehydes, or olefins. In this context, phosphoramides 2
have recently been introduced by Yamamoto et al. for cases
in which phosphoric acids are not acidic enough to activate
deficient and potentially stereocontrolling group, were
highly desirable subjects for study.1
–3,5
A careful literature research revealed only a single
bissulfonylphosphoramidimidate. In 1980, Kukhar et al. de-
scribed the synthesis of an achiral pyrocatechol derived
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 156–158

1
57
Synlett
P. S. Kaib, B. List
Letter
R1
R1
stereo controlling group
O
R2
O
S
N
N
S
PCl5 (2.0 equiv), pyridine
2
O
OH
OH
O
O
Lewis basic site
P
H
O
O
O
8
5 °C, 5 h; then R SO2NH2
Ph
OH
P
Brønsted acidic site
OH
(12 equiv),
DMAP (0.5 equiv),
O
R2
3
R1
R1
pKa ≈ 13
O
8
5 °C, 5 d
pKa = 20
C2-symmetric anion
7
6
up to 66% yield
1
Akiyama and Terada 2004
R1
R1
O
=
CF3
H
F3C
CF3
O
S
N
N
S
O
O
P
O
O
O
O
CF3
8
9
Ph
NHTf
P
pKa ≈ 6
R1
O
O
NH
S
4
pseudo-C2-symmetric anion
CF3
CF3
O
pKa = 11
O
additional electron-deficient
stereo controlling group
2
F3C
CF3
Yamamoto 2006
10
11
12
O
O
S
NTf
O
O
N
P
pKa ≈ 2 (estimated)
CF3
Ph
NHTf
NH
S
C2-symmetric anion
5
O
R1
O
R1
=
O
F3C
CF3
pKa = 6
O
S
N
N
S
CF3
CF3
6
O
O
P
H
this work
O
Scheme 1 Influence on pK values by introduction of electron-accept-
ing groups (pK in MeCN) and highly acidic BINOL-derived phosphora-
a
R1
O
13
14
a
midimidate Brønsted acids 6; Tf = SO CF
2
3
CF3
Scheme 2 General synthesis of new phosphoramidimidate Brønsted
acids 6
N,N′-bistriflylphosphoramidimidate in two steps.16 A ret-
rosynthetic analysis of our desired phosphoramidimidate 6
furnished differently substituted moisture-sensitive phos-
phorus precursors and the corresponding BINOLs 7. A direct
substitution approach on phosphorus(V) led us to start
Our newly developed route17 tolerates various substitu-
ents at the 3,3′-positions of enantiopure BINOL 7 (Scheme
2), including 2,4,6-triisopropylphenyl 8, 3,5-bis(trifluoro-
methyl) 9, naphthalen-1-yl 10, phenanthren-9-yl 11, and
3,3′′,5,5′′-tetrakis(trifluoromethyl)-[1,1′:3′,1′-terphenyl]-5′-
yl 12. Moreover, further modifications at the active center
on the NH-acidic nitrogen afforded highly hindered N,N′-
bisarylsulfonylphosphoramidimidates 13 and 14. The N,N′-
bissulfonylphosphoramidimidates displayed interesting
catalytic performances when compared to previously de-
scribed Brønsted acid catalysts, such as phosphoric acid
from commercially available PCl . We speculated that treat-
5
ment of the corresponding BINOL derivative 7 in hot pyri-
dine with PCl should generate the corresponding pentava-
5
lent compound [(RO) PCl ]. This intermediate should then
2
3
2
undergo further substitution with a sulfonamide R SO NH ,
2
2
yielding the desired N,N′-bissulfonylphosphoramidimidates
6
. Indeed, we found that treating different BINOLs 7 with
2
PCl , followed by the addition of R SO NH in hot pyridine,
5
2
2
10
proceeded smoothly to give the corresponding Yamamoto
catalysts 2 after hydrolytic workup. Apparently, the second
substitution reaction with an additional sulfonamide
TRIP (15)1
8,19
and phosphoramide 16 (Scheme 3).
For example, phosphoramidimidate 8 was found to be
significantly more active in catalyzing the diastereoselec-
tive addition of trimethylhydroquinone (TMHQ) to isophy-
2
R SO NH is significantly slower. Fortunately, we found that
2
2
20
21
prolonged heating, and the addition of N,N-dimethylpyri-
din-4-amine (DMAP), furnished the desired N,N′-bissulfon-
ylphosphoramidimidates 6 in a one-pot procedure (Scheme
tol. α-Tocopherol was generated at room temperature
after 23 hours, while TRIP (15) and phosphoramide 16 did
not catalyze the desired transformation even after exten-
sive heating.
2).
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 156–158

1
58
Synlett
P. S. Kaib, B. List
Letter
(
2) Akiyama, T.; Mori, K. Chem. Rev. 2015, 115, 9277.
HO
(3) Terada, M. Synthesis 2010, 1929.
+
(4) Kampen, D.; Reisinger, C. M.; List, B. Top. Curr. Chem. 2010, 291,
HO
OH
HO
395.
(
(
5) Akiyama, T.; Itoh, J.; Fuchibe, K. Adv. Synth. Catal. 2006, 348, 999.
6) Akiyama, T.; Itoh, J.; Yokota, K.; Fuchibe, K. Angew. Chem. Int. Ed.
TMHQ
(7R,11R)-isophytol
2004, 43, 1566.
catalyst (5 mol%)
CH2Cl2
(7) Uraguchi, D.; Terada, M. J. Am. Chem. Soc. 2004, 126, 5356.
(8) Asymmetric Organocatalysis Workbench Edition; List, B.;
Maruoka, K., Eds.; Thieme: Stuttgart, 2012.
O
(
9) Akiyama, T.; Itoh, J.; Fuchibe, K. Adv. Synth. Catal. 2006, 348, 999.
α-tocopherol
i-Pr
(
(
10) Nakashima, D.; Yamamoto, H. J. Am. Chem. Soc. 2006, 128, 9626.
11) Kaupmees, K.; Tolstoluzhsky, N.; Raja, S.; Rueping, M.; Leito, I.
Angew. Chem. Int. Ed. 2013, 52, 11569.
i-Pr
i-Pr
i-Pr
i-Pr
i-Pr
(
12) Yagupolskii, L. M.; Petrik, V. N.; Kondratenko, N. V.; Soovali, L.;
Kaljurand, I.; Leito, I.; Koppel, I. A. J. Chem. Soc., Perkin Trans. 2
2002, 1950.
i-Pr
i-Pr
O
i-Pr
NTf
O
O
O
O
O
O
O
P
P
P
OH
i-Pr
NHTf
i-Pr
NHTf
i-Pr
(13) Sai, M.; Yamamoto, H. J. Am. Chem. Soc. 2015, 137, 7091.
(
(
(
14) Kolthoff, I. M.; Chantooni, M. K. Jr. J. Phys. Chem. 1966, 70, 856.
15) Čorić, I.; List, B. Nature (London, U.K.) 2012, 483, 315.
16) Kukhar, W. P.; Grischkun, E. W.; Rubavskii, W. P.; Guljarov, W.
A. Zh. Obshch. Khim. 1980, 50, 1477.
i-Pr
i-Pr
i-Pr
16
50 °C, 24 h
0% conversion
i-Pr
i-Pr
i-Pr
1
5
8
(17) General Procedure
5
0 °C, 24 h
% conversion
23 °C, 23 h
33% conversion
d.r. = 66:34
0
In a flame-dried flask under Ar the corresponding (S)- or (R)-
BINOL derivative (1.0 equiv) was dissolved in freshly distilled
(
d.r. = 36:64 with ent-8)
pyridine (0.10 M), PCl (2.0 equiv) was added, and the mixture
5
was heated to 85 °C until full consumption of the starting mate-
rial was observed (TLC). The reaction mixture was cooled to r.t.
and CF SO NH (12 equiv) and N,N-dimethylpyridin-4-amine
Scheme 3 Preliminary exploration on the catalytic performance of
phosphoramidimidate Brønsted acids; Tf = SO CF
2
3
3
2
2
(
DMAP, 0.5 equiv) were added, and the mixture was heated to
In summary, we have designed and developed highly
acidic BINOL-derived N,N′-bistriflylphosphoramidimidate
and N,N′-bisarylsulfonylphosphoramidimidate Brønsted ac-
ids. Their application in asymmetric Brønsted acid catalysis
shows intriguing effects on acidity and reactivity and
therefore significantly higher performance compared to
previously described phosphoric acid derivatives. Investiga-
tions and more detailed studies on these new motif’s per-
formances are ongoing in our laboratories.
85 °C until full consumption was observed (TLC). The reaction
mixture was cooled to r.t., and concentrated under reduced
pressure. HCl (1.0 M) was added, and the aqueous layer was
extracted with CH Cl . The combined organic layers were
washed with brine, dried (Na SO ), filtered, and concentrated
under reduced pressure. Purification by column chromatogra-
phy (silica gel), acidification in CH Cl with HCl (6.0 M) followed
2
2
2
4
2
2
by drying under reduced pressure with toluene afforded the
phosphoramidimidates.
(18) Hoffman, S.; Seayad, A. M.; List, B. Angew. Chem. Int. Ed. 2005,
4, 7424.
4
(19) Klussmann, M.; Ratjen, L.; Hoffman, S.; Wakchaure, V.;
Goddard, R.; List, B. Synlett 2010, 2189.
Acknowledgment
(20) Bonrath, W.; Netscher, T. Appl. Catal., A 2005, 55.
We would like to thank Alberto Martínez for the support in the com-
parison studies with our new catalysts.
(21) Experimental Details
A mixture of TMHQ (5 mg, 0.03 mmol, 1.0 equiv), isophytol (9
mg, 0.03 mmol, 1.0 equiv), and catalyst 8 (2 mg, 1.5 μmol, 0.05
equiv) in CH Cl was stirred at 23 °C for 23 h. Et N (3 μL) was
2
2
3
Supporting Information
added, and the mixture was filtered through silica gel and con-
centrated under reduced pressure. Conversions were deter-
Supporting information for this article is available online at
1
mined by H NMR relative to TMHQ followed by purification on
http://dx.doi.org/10.1055/s-0035-1560971.
S
u
p
p
ortioIgnfrm oaitn
S
u
p
p
ortioIgnfrm oaitn
silica gel. Diastereomeric ratios (d.r.) were determined by HPLC
with a chiral stationary phase (Daicel Chiracel Cellucoat RP
column, 1 mL/min, 90:10 MeCN–H O, 220 nm, t = 4.00 min, t =
2
R
R
References and Notes
4.34 min).
(1) Akiyama, T. Chem. Rev. 2007, 107, 5744.
©
Georg Thieme Verlag Stuttgart · New York — Synlett 2016, 27, 156–158