Click-binol-phosphoric acid catalysts in intramolecular enantioselective oxidative C[sbnd]H-bond functionalization

Article abstract of DOI:10.1016/j.molcata.2016.09.006

Counteranion-catalysis represents an appealing but challenging approach for the development of enantioselective oxidative C[sbnd]H bond functionalization reactions. In this work, a new family of 3,3′-triazolyl BINOL-derived phosphoric acids was synthesized and employed in the intramolecular asymmetric C[sbnd]H bond functionalization of N-aryl substituted tetrahydroisoquinolines. As previously reported with related structures, the presence of the triazole groups on the catalysts was key to attain enantioselectivity. Our study also shows the importance of choosing the appropriate regioisomeric triazole groups at the BINOL backbone to achieve a more efficient chirality transfer. Moderate enantiomeric ratios were obtained with the N-benzamide substrates, whereas the change of the nature of the nucleophile fragment was translated to a dramatic loss of the enantioselectivity. Therefore, it can be foreseen that there is a need for designing further superior catalyst structures to develop future counter-anion organocatalyzed asymmetric C[sbnd]H bond functionalization reactions.

Full text of DOI:10.1016/j.molcata.2016.09.006

Accepted Manuscript
Title: CLICK-BINOL-PHOSPHORIC ACID CATALYSTS IN
INTRAMOLECULAR ENANTIOSELECTIVE OXIDATIVE
C-H-BOND FUNCTIONALIZATION
´
´
Author: Sebastian Stockerl Daniel Gutierrez Olga Garcıa
˜
Mancheno
PII:
S1381-1169(16)30378-8
DOI:
Reference:
http://dx.doi.org/doi:10.1016/j.molcata.2016.09.006
MOLCAA 10030
To appear in:
Journal of Molecular Catalysis A: Chemical
Received date:
Revised date:
Accepted date:
6-6-2016
2-9-2016
3-9-2016
´
´
˜
Please cite this article as: Sebastian Stockerl, Daniel Gutierrez, Olga Garcıa Mancheno,
CLICK-BINOL-PHOSPHORIC ACID CATALYSTS IN INTRAMOLECULAR
ENANTIOSELECTIVE OXIDATIVE C-H-BOND FUNCTIONALIZATION, Journal
of Molecular Catalysis A: Chemical http://dx.doi.org/10.1016/j.molcata.2016.09.006
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Journal of Molecular Catalysis A: Chemical
CLICK-BINOL-PHOSPHORIC ACID CATALYSTS IN INTRAMOLECULAR
ENANTIOSELECTIVE OXIDATIVE C-H-BOND FUNCTIONALIZATION
Sebastian Stockerl,1 Daniel Gutiérrez,1 Olga García Mancheño*1,2
1 Institute for Organic Chemistry, University of Regensburg, 93053 Regensburg.
2 Straubing Center of Science for Renewable Resources, 94315 Straubing.
*corresponding author: olga.garcia-mancheno@ur.de
Graphical abstract

Research highlights:
► synthesis of a new family of C2-symmetric triazole-phosphoric acid catalysts.
► intramolecular asymmetric C-H bond functionalization of N-aryl substituted
tetrahydroisoquinolines.
► important effects of the triazoles and the regiomeric structures for optimal enantioselectivity.
► π−π vs. cooperative π−π and triazole-substrate interactions.
Abstract:
Counteranion-catalysis represents an appealing but challenging approach for the development of
enantioselective oxidative C-H bond functionalization reactions. In this work, a new family of 3,3′-
triazolyl BINOL-derived phosphoric acids was synthesized and employed in the intramolecular
asymmetric C-H bond functionalization of N-aryl substituted tetrahydroisoquinolines. As previously
reported with related structures, the presence of the triazole groups on the catalysts was key to
attain enantioselectivity. Our study also shows the importance of choosing the appropriate
regioisomeric triazole groups at the BINOL backbone to achieve a more efficient chirality transfer.
Moderate enantiomeric ratios were obtained with the N-benzamide substrates, whereas the change
of the nature of the nucleophile fragment was translated to a dramatic loss of the enantioselectivity.
Therefore, it can be foreseen that there is a need for designing further superior catalyst structures to
develop future counter-anion organocatalyzed asymmetric C-H bond functionalization reactions.
Keywords: C-H functionalization, oxidation, organocatalysis, enantioselective, heterocycles
Introduction
In the last few years, selective C–H bond functionalization has attracted great interest, such as the
cross-dehydrogenative coupling (CDC) coined by C.-J. Li,[1] since it offers not only more
straightforward approaches but also new possibilities in synthetic chemistry.[2,3] The growing
demand on innovative and simple direct C–H bond transformations has led to important
breakthroughs in the chemistry of oxidative C(sp3)–H functionalization.[2-4] Our research group has
also contributed to this field by developing novel, mild oxidative reactions for the synthesis of
valuable (bioactive)heterocycles.[5] Thus, we have recently introduced the use of TEMPO
oxoammonium salts (T+X-)[6,7] as alternative mild and efficient oxidants for C–C bond forming
reactions of C(sp3)–H bonds, allowing in some cases to overcome certain substrate or product
incompatibilities with the classically used oxidants. Additionally, recent efforts towards the
development of enantioselective C(sp3)–H bond functionalization have been made.[8] Besides the
initially explored metal-catalyzed reactions,[9] organocatalysis represents a powerful approach.[10]

Most of the reported examples rely on covalent amino-catalysis, which limit its applicability to
carbonyl compounds. Considering that the key intermediate in this type of transformations is an ionic
species such as an iminium ion, counteranion organocatalysis has recently been embraced
(Scheme 1).[11] The first intramolecular C-H functionalization approach was based on the use of
chiral phosphoric acids (PA)[12] to generate in situ the active phosphate catalyst responsible for the
formation of a chiral close ion-pair and the enantioselectivity control.[13] Shortly after, the
combination of metal-photocatalysis and a chiral thiourea as anion-binding catalyst was utilized for
the intermolecular functionalization of N-aryl tetrahydroisoquinolines (THIQs).[14]
Despite of the tremendous interest that counter-anion catalysis is currently evoking in the synthetic
scientific community,[11] a still limited number of effective catalyst motifs is available. Aiming at
providing alternative novel structures, we recently developed a modular strategy to introduce 1,2,3-
triazole moieties into BINOL derivatives (Click-BINOLs), which were employed as ligands in
asymmetric Lewis acid metal catalysis (Figure 1, bottom).[15] Later on, the group of Toste[13]
reported the performance of phosphoric acids derived from the regioisomeric 3,3’-triazolyl BINOLs
(Figure 1, top-right) as superior organocatalysts in the enantioselective C–H bond functionalization
of tetrahydroisoquinoline-N-benzamides as shown in Scheme 1.[16] As part of our ongoing research
program devoted to the development of asymmetric C-H bond functionalization reactions, we herein
described our latest results in the area of counteranion-catalysis using a new family of chiral Click-
BINOL-based phosphates (Figure 1, top-left).
Experimental
General Information
13
1H and C NMR spectra were recorded in CDCl3 (reference signals:[17] 1H = 7.26 ppm, 13C = 77.16
ppm, CDCl3) on a Bruker ARX-300 and a Varian AV-300, 400 or 600 MHz. Chemical shifts (δ) are
given in ppm and spin-spin coupling constants (J) are given in Hz. Analytical thin layer
chromatography was performed using silica gel 60 F254 and a solution of KMnO4 or
phosphomolybdic acid served as staining agent. Column chromatography was performed on silica
gel 60 (0.040-0.063 mm). Exact masses (HRMS) were recorded on an Agilent Q-TOF 6540 UHD
spectrometer (samples in CH3OH as solvent) using electrospray (ES) or chemical (CI) ionization
techniques. Chiral High Pressure Liquid Chromatography (HPLC) analyses were performed on an
Agilent 1200 series instrument.
Synthesis of PA Catalysts:

Synthesis of alkynes:
2,4,6-Triisopropylbenzaldehyde[18]
A stirring solution of 1-bromo-2,4,6-triisopropylbenzene (5.25 ml, 20.0 mmol, 1.0 eq.) in dry THF
(40 ml) was cooled to -78 °C. n-BuLi (1.6 M in hexane; 13.8 ml, 22.0 mmol, 1.1 eq.) was added over
20 min. After stirring for additional 20 min, dry DMF (1.8 ml, 22.0 mmol, 1.1 eq.) was added slowly.
The reaction mixture was stirred 15 min at -78 °C, allowed to warm to -10 °C and quenched with
H2O (20 ml). The aqueous layer was extracted with ether (3 x 20 ml) and dried over Na2SO4.
Purification by column chromatography using PE/EtOAc (10:1) as eluent gave the title compound
1
(3.6 g, 15.6 mmol, 78%) as a colorless oil. Rf = 0.66 (10:1) (SiO2, PE/EtOAc). H-NMR (300 MHz,
CDCl3) δ[ppm]: 10.66 (s, 1H), 7.11 (s, 2H), 3.60 (sept., J = 6.8 Hz, 2H), 2.92 (sept., J = 6.9 Hz, 1H),
1.27 (d, J = 6.9 Hz, 6H), 1.26 (d, J = 6.9 Hz, 6H). The analytical data are in accordance with the
literature.
2,4,6-Triisopropylphenyl acetylene[19]
A stirring, degassed solution of triphenylphosphine (15.9 g, 60.0 mmol, 4.0 eq.) and carbon
tetrabromide (10.2 g, 30.0 mmol, 2.0 eq.) in dry dichloromethane (200 ml) was cooled to 0 °C and
2,4,6-triisopropylphenylbenzaldehyde (3.6 g, 15.0 mmol, 1.0 eq.) was added. The reaction mixture
was allowed to warm to rt overnight. The solids were filtered off and the solvent was removed under
reduced pressure. PE (400 ml) was added and after trituration the solution was filtered over a silica
plug using PE as eluent. The solvent was removed under reduced pressure and the crude
intermediate was dissolved in dry THF (50 ml). The reaction mixture was cooled to -78 °C, n-BuLi
(1.6 M in hexane; 11.8 ml, 18.75 mmol, 1.25 eq.) was added dropwise. After 1 h, the reaction
mixture was allowed to warm to rt and quenched with sat. aq. NH4Cl (30 ml). The aqueous layer was
extracted with PE (3 x 40 ml). The solvent was removed under reduced pressure and the crude
alkyne was filtered over a silica plug using PE as eluent. A small crystal of hydrochinone was added
and the solvent was removed to give the title compound (2.5 g, 10.9 mmol, 73%) as a pale purple
1
oil. H-NMR (300 MHz, CDCl3) δ[ppm]: 6.98 (s, 2H), 3.54 (sept., J = 6.9 Hz, 2H), 3.42 (s, 1H), 2.89
(sept., J = 6.9 Hz, 1H), 1.26 (d, J = 6.8 Hz, 6H), 1.25 (d, J = 6.9 Hz, 6H). The analytical data are in
accordance with the literature.
1-((3r,5r,7r)-Adamantan-1-yl)ethan-1-one[20]
A stirring solution of adamantyl carboxylic acid (1.8 g, 10.0 mmol, 1.0 eq.) in thionyl chloride (4.0 ml,
55.1 mmol, 5.51 eq.) was refluxed for 4 h. The excess of thionyl chloride was removed under
reduced pressure to give the 1-adamantanecarbonyl chloride. Diethylmalonate (2.5 g, 2.4 ml,
15.5 mmol, 1.55 eq.) in PE (5 ml) was added dropwise to a stirring solution of sodium (0.35 g,
15.5 mmol, 1.55 eq.) in PE (10 ml). After complete consumption of sodium, carbonyl chloride in PE
(5 ml) was added slowly and the resulting reaction mixture was stirred overnight at rt. Distilled water

(20 ml) was added, the organic layer was separated and concentrated under vacuum. Acetic acid
(8 ml), water (2.4 ml) and sulfuric acid (0.8 ml) were added and the reaction mixture was refluxed for
6 h. The solution was poured into ice water (60 ml) for crystallization. The resulting crystals were
filtered off and dried under vacuum to give the title compound (0.8 g, 4.8 mmol, 48%) as white
1
needles. H-NMR (300 MHz, CDCl3) δ[ppm]: 2.07 (s, 3H), 2.04 – 2.01 (m, 3-H), 1.78 (d, J = 2.8 Hz,
6H), 1.73 - 1.61 (m, 6H). The analytical data are in accordance with the literature.
(3r,5r,7r)-1-Ethynyladamantane[21]
A stirring solution of diisopropyl amine (0.8 ml, 5.7 mmol, 1.19 eq.) in dry THF (7 ml) was cooled
to -78 °C followed by dropwise addition of n-BuLi (1.6 M in hexane; 3.25 ml, 5.2 mmol, 1.08 mmol)
and was stirred for 1 h. Adamantyl methyl ketone (0.85 g, 4.8 mmol, 1.0 eq.) in dry THF (3 ml) was
added at -78 °C to the LDA solution. After 1 h, chloro diethyl phosphate (0.86 g, 5.0 mmol, 1.05 eq.)
was added dropwise. The resulting reaction mixture was allowed to warm to rt and stirred for 3 h. A
second LDA solution was prepared as already described from diisopropyl amine (1.4 ml, 9.5 mmol,
1.98 eq.) in THF (15 ml) and n-BuLi (1.6 M in hexane; 6.4 ml, 10.3 ml, 2.15 eq.) at -78 °C. After 3 h
the reaction mixture was added to the second LDA solution at -78 °C, allowed to warm to rt and
stirred overnight. The reaction mixture was quenched with H2O (20 ml) and the aqueous layer was
extracted with PE (4 x 15 ml). The combined organic layers were washed with ice-cold 1 M HCl
(2 x 15 ml), sat. aq. NaHCO3 (2 x 20 ml) (pH should be 9) and dried over Na2SO4. The solution was
filtered over Celite and the solvent was removed under reduced pressure. Purification by filtration
over a silica plug using PE as eluent gave the title compound (0.44 g, 2.8 mmol, 58%) as a colorless
1
oil. H-NMR (300 MHz, CDCl3) δ[ppm]: 2.10 (s, 1H), 1.99 – 1.93 (m, 3H), 1.89 (d, J = 2.8 Hz, 6H),
1.69 (t, J = 3.1 Hz, 6H)). The analytical data are in accordance with the literature.
4-Bromo-2,6-diisopropylaniline[22]
A solution of Br2 (2.1 mL, 41.0 mmol, 1.05 eq.) in CH2Cl2/MeOH (100 mL, 1:1 v/v) was added to a
stirring solution of 2,6-diisopropylaniline (7.4 mL, 39.0 mmol, 1.0 eq.) in CH2Cl2/MeOH (200 mL, 1:1
v/v) at r.t. over 2 h. The orange-red solution was stirred for 1 day. The solvents were evaporated and
the resultant pink solid was washed with PE and further recristallized from CH2Cl2/PE to give the title
1
compound as light orange-red solid (7.8 g, 28.1 mmol, 72%). H-NMR (300 MHz, CDCl3) δ[ppm]:
10.08 (s, 2H), 7.36 (s, 2H), 3.80 - 3.62 (m, 2H), 1.29 (d, J = 6.7 Hz, 12H). The analytical data are in
accordance with the literature.
5-Bromo-2-iodo-1,3-diisopropylbenzene[23]
To a solution of 4-bromo-3,5-dimethylaniline (8.0 g, 40 mmol, 1.0 eq.) in aq. H2SO4 (360 mL, 6.0 M)
at –15 °C, a solution of NaNO2 (5.6 g, 80 mmol, 2.0 eq.) in H2O (32 mL) was added dropwise over a
period of 20 min. The resulting mixture was stirred at –15 °C for an additional 15 min. Then, a
solution of KI (16.6 g, 100.0 mmol, 2.5 eq.) in H2O (320 mL) was slowly added in portions to the

mixture over a period of 25 min. The reaction mixture was stirred at -10 °C for 30 min, then stirred at
0 °C for 4 h. After the mixture was stirred overnight at room temperature, the resulting mixture was
neutralized by adding Na2CO3. The mixture was subsequently extracted with Et2O (2 x 200 mL). The
combined organic layers were washed with H2O (200 mL), aq. Na2SO3 (1 M, 2 x 100 mL), aq. NaOH
(2.5 M, 2 x 100 mL) and H2O (100 mL), dried over Na2SO4 and the solvent was removed under
reduced pressure. The residue was purified by column chromatography using PE as eluent,
providing the title compound (6.4 g, 22.4 mmol, 56%) as colorless oil. The analytical data are in
accordance with the literature.
((4-Bromo-2,6-diisopropylphenyl)ethynyl)trimethylsilane[23]
PdCl2(PPh3)2 (0.13 g, 0.19 mmol, 1.2 mol%), CuI (72 mg, 0.38 mmol, 2.4 mol%) and H2O (0.5 ml,
27.0 mmol, 1.7 eq.) were added to a solution of 5-bromo-2-iodo-1,3-diisopropylbenzene (5.8 g,
15.8 mmol, 1.0 eq.) and trimethylsilylacetylene (4.1 g, 22.0 mmol, 1.4 eq.) in degassed piperidine
(30 mL) at 0 °C under an argon atmosphere. The reaction mixture was stirred at 0 °C for 1 h and for
an additional 2 h at r.t. After filtration over Celite, the solvent was removed under reduced pressure.
The residue was dissolved in 1 M HCl (30 ml) and Et2O (30 ml). The organic layer was washed with
brine (2 x 20 ml), dried over Na2SO4 and the solvent was removed under reduced pressure. The
residue was purified by column chromatography using PE as an eluent to give the title compound
(2.5 g, 7.4 mmol, 47%) as colorless oil. 1H-NMR (300 MHz, CDCl3) δ[ppm]: 7.23 (s, 2H), 3.47 (sept.,
J = 6.8 Hz, 2H), 1.25 (d, J = 6.9 Hz, 12H), 0.28 (s, 9H). 13C-NMR (100 MHz, CDCl3) δ[ppm]: 147.9,
127.7, 127.2, 122.1, 104.9, 94.1, 33.5, 22.9, 0.0. HRMS (EI): m/z [M] calcd for C17H25BrSi :
336.0909; found: 336.0894.
5-Bromo-2-ethynyl-1,3-diisopropylbenzene[23]
K2CO3 (3.0 g, 21.0 mmol, 2.8 eq.) was added to a solution of ((4-bromo-2,6-diisopropylphenyl)
ethynyl)trimethylsilane (2.5 g, 7.4 mmol, 1.0 eq.) in dry MeOH (25 mL) under an argon atmosphere
and the mixture was stirred at 40 °C for 24 h. Sat. aq. NH4Cl solution (100 mL) and pentane
(100 mL) were added to the mixture and the layers were separated. The organic layer was washed
with H2O (2 x 50 ml), dried over Na2SO4 and the solvent was removed under reduced pressure.
Purification by column chromatography using PE as an eluent gave the title compound (1.5 g,
1
4.7 mmol, 64%) as colorless oil. H-NMR (300 MHz, CDCl3) δ[ppm]: 7.22 (s, 2H), 3.44 (sept.,
J = 6.8 Hz, 2H), 3.07 (s, 1H), 1.21 (d, J = 6.8 Hz, 12H). 13C-NMR (100 MHz, CDCl3) δ[ppm]: 148.1,
127.9, 127.5, 121.1, 83.6, 77.2, 33.5, 22.9. HRMS (EI): m/z [M] calcd for C14H17Br : 264.0514;
found: 264.0510.
Introduction of the side-chain:
(S)-6,6'-Dibromo-[1,1'-binaphthalene]-2,2'-diol (6-Br-BINOL)[24]

(S)-BINOL (7.20 g, 25.0 mmol, 1.0 eq.) was suspended in CH2Cl2 (250 mL) at -78 °C. A solution of
Br2 (3.9 mL, 34.0 mmol, 1.4 eq.) in CH2Cl2 (40 mL) was added dropwise to the reaction (over 20-30
min) and stirred further 15 min at -78 °C. The mixture was then let to reach r.t. and reacted until full
conversion was observed by TLC (aprox. 3 h). A sat. aq. solution of Na2S2O3 (50 mL) was added
and the aqueous layer extracted with EtOAc (3 x 50 mL). The combined organic layers were dried
over MgSO4, filtered and the solvent was removed under reduced pressure. Recrystallization from
1
CH2Cl2/pentane gave the title compound as a white solid (10.34 g, 23.3 mmol, 93%). H-NMR
(300 MHz, CDCl3) δ[ppm]: 8.03 (d, J = 1.9 Hz, 2H), 7.87 (d, J = 9.0 Hz, 2H), 7.45 – 7.35 (m, m 4H),
6.94 (d, J = 9.0 Hz, 2H), 5.00 (bs, 2H). 13C-NMR (75MHz, CDCl3) δ[ppm]: 153.0, 131.9, 130.8,
130.7, 130.6, 130.4, 125.9, 119.0, 118.0, 110.7. The analytical data are in accordance with the
literature.
(S)-6,6'-Dibromo-2,2'-bis(methoxymethoxy)-1,1'-binaphthalene (7)[25]
A stirring solution of NaH (60 % in mineral oil, 1.5 g, 37.5 mmol, 2.5 eq.) in a mixture of THF-DMF
(2:1, 45 ml) was cooled to 0 °C. (S)- 6-Br-BINOL (6.7 g, 15.0 mmol, 1.0 eq.) in THF (10 ml) was
added dropwise and the resulting solution was stirred at rt for 1 h. Chloro(methoxy)methane (4.2 g,
52.5 mmol, 3.5 eq.) was added and the reaction mixture was stirred at rt for 4 h. The solution was
quenched with H2O (50 ml) and extracted with EtOAc (3 x 50 ml). The combined organic layers were
washed with brine, dried over Na2SO4 and the solvent was removed under reduced pressure.
Recrystallization from MeOH gave the title compound (7.1 g, 13.3 mmol, 89%) as a yellow solid.
1H-NMR (400 MHz, CDCl3) δ[ppm]: 8.03 (d, J = 1.9 Hz, 2H), 7.86 (d, J = 9.1 Hz, 2H), 7.59 (d,
J = 9.1 Hz, 2H), 7.29 (dd, J = 9.0, 2.0 Hz, 2H), 6.98 (d, J = 9.0 Hz, 2H), 5.09 (d, J = 6.9 Hz, 2H),
4.98 (d, J = 6.9 Hz, 2H), 3.16 (bs, 6H). The analytical data are in accordance with the literature.
General procedure A: Grignard reaction
A stirring solution of dibromo-MOM-BINOL 132 (1.0 eq.) and PdCl2(dppf) (5 mol%) in THF (200 ml)
was cooled to 0 °C. n-Alkyl-MgX (5 eq.) was added dropwise and the reaction mixture was refluxed
for 3 h. The solution was allowed to cool to room temperature, was quenched with sat. aq. NH4Cl
(150 ml) and was extracted with EtOAc (3 x 100 ml). The combined organic layers were washed
with brine (100 ml), dried over Na2SO4 and the solvent was removed under reduced pressure.
Purification by column chromatography using PE/EtOAc as eluent gave desired products.
(S)-2,2'-Bis(methoxymethoxy)-6,6'-dioctyl-1,1'-binaphthalene (8)[13]
Following the General Procedure A, subjection of dibromo-MOM-BINOL 7 (6.9 g, 13.0 mmol,
1.0 eq.) and n-Oct-MgBr (2.0 M in Et2O, 32.5 ml, 65.0 mmol, 5 eq.), provided after purification by
column chromatography [PE/EtOAc (5:1)] the title compound (7.6 g, 12.7 mmol, 98%) as a yellow
1
oil. Rf = 0.52 (5:1) (SiO2, PE/EtOAc). H-NMR (400 MHz, CDCl3) δ[ppm]: 7.86 (d, J = 9.0 Hz, 2H),

7.62 (s, 2H), 7.52 (d, J = 9.0 Hz, 2H), 7.07 (s, 4H), 5.04 (d, J = 6.7 Hz, 2H), 4.94 (d, J = 6.7 Hz, 2H),
3.13 (s, 6H), 2.72 - 2.68 (m, 4H), 1.70 - 1.60 (m, 4H), 1.36 - 1.20 (m, 20H), 0.89 - 0.85 (m, 6H). The
analytical data are in accordance with the literature.
(S)-2,2’-Bis(methoxymethoxy)-6,6’-didodecyl-1,1’-binaphthalene (9)[26]
Following the General Procedure A, subjection of dibromo-MOM-BINOL 7 (1.8 g, 3.3 mmol, 1.0 eq.)
and n-dodecyl-MgBr (1.5 M in Et2O, 11 ml, 16.5 mmol, 5 eq.), provided after purification by column
chromatography [PE/EtOAc (10:1)] the title compound (2.0 g, 2.8 mmol, 85%) as a yellow oil. Rf =
1
0.53 (10:1) (SiO2, PE/EtOAc). H-NMR (300 MHz, CDCl3) δ[ppm]: 7.99 (d, J = 9.0 Hz, 2H), 7.79 (s,
2H), 7.76 - 7.64 (m, 2H), 7.42 - 7.18 (m, 4H), 5.17 (d, J = 6.6 Hz, 2H), 5.08 (d, J = 6.5 Hz, 2H), 3.27
(s, 6H), 2.88 (s, 4H), 1.86 (s, 4H), 1.64 – 1.43 (m, 36H), 1.10 (d, J = 5.1 Hz, 6H). The analytical data
are in accordance with the literature.
(S)-2,2'-Bis(methoxymethoxy)-6,6'-dioctadecyl-1,1'-binaphthalene (10)
Following the General Procedure A, subjection of dibromo-MOM-BINOL 7 (1.8 g, 3.3 mmol, 1.0 eq.)
and n-octadecyl-MgCl (0.5 M in Et2O, 33 ml, 16.5 mmol, 5 eq.), provided after purification by column
chromatography [PE/EtOAc (10:1)] the title compound (2.9 g, 3.2 mmol, 99%) as a yellow oil. Rf =
1
0.44 (10:1) (SiO2, PE/EtOAc). H-NMR (300 MHz, CDCl3) δ[ppm]: 7.88 (d, J = 9.0 Hz, 2H), 7.64 (s,
2H), 7.54 (d, J = 9.0 Hz, 2H), 7.09 (s, 4H), 5.07 (d, J = 6.4 Hz, 2H), 4.98 (d, J = 6.4 Hz, 2H), 3.15 (s,
6H), 2.78 - 2.66 (m, 4H), 1.80 - 1.61 (m, 4H), 1.27 (bs, 60H), 0.89 (t, J = 6.7 Hz, 6H). 13C-NMR
(100 MHz, CDCl3) δ[ppm]: 152.1, 138.6, 132.5, 130.1, 128.9, 128.8, 128.0, 126.2, 125.6, 121.6,
117.5, 117.4, 95.5, 55.9, 55.8, 35.9, 32.0, 31.4, 29.8, 29.7, 29.6, 29.5, 29.4, 22.7, 14.2. HRMS (ESI):
m/z [M + Na]+ calcd for C60H94O4 + Na: 901.7044; found: 901.7035.
General Procedure B: Synthesis of Diazido-MOM-BINOLs[15a]
To a magnetically stirred solution of the corresponding MOM-BINOL (4.50 mmol, 1.00 eq.) and
TMEDA (2.09 g, 18.00 mmol, 4.00 eq.) in Et2O (100 ml), n-BuLi (1.6 M in pentane, 7.7 ml,
12.38 mmol, 2.75 eq.) was added dropwise at 0 °C. The reaction mixture was allowed to stir at room
temperature for 1 h and was cooled to 0 °C again. Then, TsN3 (2.66 g, 13.50 mmol, 3.00 eq.) was
added dropwise and the reaction mixture was kept at 0 °C. After 1 h, the cooling bath was removed
and the solution was stirred at room temperature for 18 h. The reaction mixture was diluted with
water (20 ml) and aqueous layer was extracted with CH2Cl2 (3 x 40 ml). The combined organic
layers were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The
products were obtained by column chromatography on silica gel using petroleum ether
(PE)/EtOAc/CH2Cl2 (30:2:1 → 20:2:1) as eluent.
(S)-3,3'-Diazido-2,2'-bis(methoxymethoxy)-1,1'-binaphthalene (4)[15a]

Following the General Procedure B, subjection of (S)-MOM-BINOL (1.66 g, 4.5 mmol, 1.0 eq.) with
subsequent purification by column chromatography using PE/EtOAc/CH2Cl2 (30:2:1 → 20:2:1) as
eluent gave the title compound (1.60 g, 3.5 mmol, 78%) as a brown solid. Rf = 0.42 (30:2:1) (SiO2,
1
PE/EtOAc/CH2Cl2). H-NMR (400 MHz, CDCl3) δ[ppm]: 7.82 (d, J = 8.2 Hz, 2H), 7.68 (s, 2H), 7.43
(ddd, J = 11.7, 5.8, 2.4 Hz, 2H), 7.25-7.21 (m, 2H), 7.15 (d, J = 8.5 Hz, 2H), 4.87 (d, J = 5.8 Hz, 2H),
4.76 (d, J = 5.8 Hz, 2H), 2.65 (bs, 6H). 13C-NMR (100 MHz, CDCl3) δ[ppm]: 145.7, 133.1, 131.3,
130.8, 127.2, 126.7, 126.4, 126.0, 126.0, 117.7, 98.9, 56.4. The analytical data are in accordance
with the literature.
(S)-3,3'-Diazido-2,2'-bis(methoxymethoxy)-6,6'-dioctyl-1,1'-binaphthalene (11)
Following the General Procedure B, subjection of dioctyl-MOM-BINOL 8 (7.6 g, 12.7 mmol, 1.0 eq.)
with subsequent purification by column chromatography using PE/EtOAc/CH2Cl2 (30:2:1) as eluent
gave the title compound (8.1 g, 11.9 mmol, 94%) as a brown oil. Rf = 0.63 (20:2:1) (SiO2,
1
PE/EtOAc/CH2Cl2). H-NMR (300 MHz, CDCl3) δ[ppm]: 7.65 (s, 2H), 7.60 (s,2H), 7.12 (s, 4H), 4.89
(dd, J = 5.8, 1.0 Hz, 2H), 4.78 (dd, J = 5.8, 1.0 Hz, 2H), 2.74 (t, J = 7.6 Hz, 4H), 2.69 (s, 6H),
1.77 - 1.64 (m, 4H), 1.30 (bs, 20H), 0.95 - 0.85 (m, 6H). 13C-NMR (100 MHz, CDCl3) δ[ppm]: 145.1,
145.1, 140.7, 133.0, 131.1, 129.8, 127.6, 127.2, 126.3, 125.1, 117.2, 98.9, 56.4, 35.9, 32.0, 31.9,
31.2, 29.8, 29.7, 29.5, 29.4, 29.3, 22.8, 22.7, 22.7, 14.1, 11.5. HRMS (ESI): m/z [M + Na]+ calcd for
C40H52N6O4 + Na: 703.3942; found: 703.3940.
3,3'-Diazido-2,2'-bis(methoxymethoxy)-6,6'-didodecyl-1,1'-binaphthalene (12)
Following the General Procedure B, subjection of dodecyl-MOM-BINOL 9 (2.0 g, 2.8 mmol, 1.0 eq.)
with subsequent purification by column chromatography using PE/EtOAc/CH2Cl2 (30:2:1) as eluent
gave the title compound (2.1 g, 2.7 mmol, 99%) as a brown oil. Rf = 0.50 (30:2:1) (SiO2,
PE/EtOAc/CH2Cl2). 1H-NMR (300 MHz, CDCl3) δ[ppm]: 7.88- 7.82 (m, 2H), 7.60 (d, J = 3.2 Hz, 2H),
7.41 (d, J = 8.1 Hz, 2H), 7.09 - 7.04 (m, 2H), 5.24 - 4.63 (m, 4H), 2.79 - 2.60 (m, 4H), 2.47 (s, 6H),
1.67 – 1.60 (m, 4H), 1.32 – 1.23 (m, 36H), 0.91 - 0.78 (m, 6H). 13C-NMR (75 MHz, CDCl3) δ[ppm]:
152.2, 152.1, 146.2, 144.6, 140.5, 138.7, 138.6, 135.6, 133.3, 133.0, 132.9, 132.4, 131.2, 130.3,
130.1, 129.8, 129.3, 128.7, 128.3, 127.9, 127.6, 127.3, 126.2, 126.0, 125.5, 125.4, 125.1, 121.6,
120.0, 117.5, 117.1, 116.8, 116.5, 98.9, 95.5, 95.1, 70.4, 56.5, 56.4, 55.9, 55.8, 35.8, 31.9, 31.3,
31.2, 31.2, 30.8, 29.8, 29.7, 29.6, 29.5, 29.4, 29.3, 22.7, 21.7, 21.6, 18.6, 14.1, 13.4. HRMS (ESI):
m/z [M + Na]+ calcd for C48H68N6O4 + Na: 815.5194; found: 815.5187.
3,3'-Diazido-2,2'-bis(methoxymethoxy)-6,6'-dioctadecyl-1,1'-binaphthalene (13)
Following the General Procedure B, subjection of octadecyl-MOM-BINOL 10 (2.9 g, 3.2 mmol,
1.0 eq.) with subsequent purification by column chromatography using PE/EtOAc/CH2Cl2 (30:2:1) as
eluent gave the title compound (2.2 g, 2.3 mmol, 70%) as a brown oil. Rf = 0.38 (30:2:1) (SiO2,
PE/EtOAc/CH2Cl2). 1H-NMR (300 MHz, CDCl3) δ[ppm]: 7.89 - 7.83 (m, 2H), 7.62 - 7.55 (m, 2H), 7.41

(d, J = 8.0 Hz, 2H), 7.07 (s, 2H), 4.84 (d, J = 5.8 Hz, 2H), 4.73 (d, J = 5.9 Hz, 2H), 2.77 - 2.67 (m,
4H), 2.65 (s, 6H), 1.66 (s, 4H), 1.25 (bs, 60H), 0.88 (t, J = 6.7 Hz, 6H). 13C-NMR (75 MHz, CDCl3)
δ[ppm]: 145.0, 140.8, 132.9, 131.0, 130.3, 129.7, 127.6, 127.1, 126.3, 125.0, 117.1, 98.9, 56.4,
35.9, 32.0, 31.1, 29.7, 29.6, 29.5, 29.4, 22.7, 21.8, 14.2. HRMS (ESI): m/z [M + Na]+ calcd for
C60H92N6O4 + Na: 983.7072; found: 983.7064.
General Procedure C: Copper-catalyzed cycloaddition of azides with alkynes (CuAAC)
A stirring solution of azide (1.0 eq.), the corresponding alkyne (3 eq.), 0.04 M aq. CuSO4 (8 mol%)
and 0.12 M aq. sodium ascorbate (24 mol%) in a mixture of CH2Cl2/t-BuOH/H2O (1:1:1; 15-30 ml;
H2O from the CuSO4 and sodium ascorbate stock solution) was heated to 50 °C. After complete
consumption of the starting material as judged by TLC, the reaction mixture was allowed to cool to
room temperature, was diluted with water (8 ml) and the aqueous layer was extracted with CH2Cl2
(3 x 8 ml). The combined organic layers were washed with 25% aq. ammonia (3 x 8 ml) and brine
(8 ml). The organic layer was dried over Na2SO4, filtered and the solvent was removed under
reduced pressure. Purification by column chromatography gave the desired products.
(S)-1,1'-(2,2'-Bis(methoxymethoxy)-[1,1'-binaphthalene]-3,3'-diyl)bis(4-phenyl-1H-1,2,3-
triazole) (5a)[15a]
Following the General Procedure C, subjection of 3,3’-diazido-MOM-BINOL 4 (0.90 g, 2.0 mmol,
1.0 eq.) and phenylacetylene (0.62 g, 6.0 mmol, 3.0 eq.) with subsequent purification by column
chromatography using PE/EtOAc (20:1) as eluent gave the title compound (0.97 g, 1.5 mmol, 75%)
as a grey solid. Rf = 0.29 (20:1) (SiO2, PE/EtOAc). 1H-NMR (400 MHz, CDCl3) δ[ppm]: 8.52 (s, 2H),
8.45 (s, 2H), 8.03 (d, J = 8.1 Hz, 2H), 7.96 (t, J = 11.1, 4.0 Hz, 4H), 7.60 - 7.54 (m, 2H), 7.52 - 7.42
(m, 6H), 7.41 - 7.30 (m, 4H), 4.51 (d, J = 5.8 Hz, 2H), 4.40 (d, J = 5.8 Hz, 2H), 2.57 (s, 6H).
13C-NMR (100 MHz, CDCl3) δ[ppm]: 148.1, 146.4, 133.7, 130.4, 130.3, 129.0, 128.7, 128.5, 128.3,
126.8, 126.3, 126.2, 125.9, 122.2, 99.6, 60.4, 56.7, 21.1, 14.2. The analytical data are in accordance
with the literature.
(S)-1,1'-(2,2'-Bis(methoxymethoxy)-[1,1'-binaphthalene]-3,3'-diyl)bis(4-mesityl-1H-1,2,3-
triazole) (5b)[15a]
Following the General Procedure C, subjection of 3,3’-diazido-MOM-BINOL 4 (0.46 g, 1.0 mmol,
1.0 eq.) and mesitylacetylene (0.44 g, 3.0 mmol, 3.0 eq.) with subsequent purification by column
chromatography using PE/EtOAc (20:1) as eluent gave the title compound (0.26 g, 0.35 mmol, 35%)
1
as a grey solid. Rf = 0.38 (20:1) (SiO2, PE/EtOAc). H-NMR (400 MHz, CDCl3) δ[ppm]: 8.50 (d,
J = 6.5 Hz, 2H), 8.25 - 8.17 (m, 2H), 7.73 (s, 1H), 7.50 - 7.31 (m, 4H), 7.30 - 7.19 (m, 3H), 6.97 (s,
4H), 4.43 (m, 4H), 2.54 (s, 3H), 2.49 (s, 3H), 2.33 (s, 6H), 2.20 (bs, 12H). The analytical data are in
accordance with the literature.

(S)-1,1'-(2,2'-Bis(methoxymethoxy)-6,6'-dioctyl-[1,1'-binaphthalene]-3,3'-diyl)bis(4-mesityl-1H-
1,2,3-triazole) (5c)
Following the General Procedure C, subjection of 3,3’-diazido-MOM-BINOL 11 (1.44 g, 2.11 mmol,
1.0 eq.) and mesitylacetylene (0.91 g, 6.32 mmol, 3.0 eq.) with subsequent purification by column
chromatography using PE/EtOAc (4:1) as eluent gave the title compound (0.97 g, 1.01 mmol, 48%)
as a brown solid. Rf = 0.55 (4:1) (SiO2, PE/EtOAc). 1H-NMR (400 MHz, CDCl3) δ[ppm]: 8.36 (s, 1H),
8.07 (s, 1H), 7.99 (s, 1H), 7.75 (s, 1H), 7.71 (s, 1H), 7.64 (s, 1H), 7.24 - 7.21 (m, 2H), 7.15 (dd,
J = 8.7, 1.5 Hz, 1H), 6.99 (s, 2H), 6.95 (d, J = 8.7 Hz, 1H), 6.79 (d, J = 19.1 Hz, 2H), 4.52 (d,
J = 5.3 Hz, 1H), 4.41 (d, J = 5.3 Hz, 1H), 4.04 (d, J = 5.9 Hz, 1H), 3.99 (d, J = 5.9 Hz, 1H),
2.79 - 2.68 (m, 4H), 2.48 (s, 3H), 2.35 (s, 3H), 2.22 (bs, 7H), 2.19 (s, 3H), 2.16 (s, 3H), 2.03 (s, 3H),
1.75 - 1.64 (m, 6H), 1.41 - 1.18 (m, 20H), 0.88 (t, J = 6.8 Hz, 6H). 13C-NMR (100 MHz, CDCl3)
δ[ppm]: 147.7, 145.7, 145.6, 141.3, 141.2, 139.2, 138.8, 138.7, 138.3, 138.1, 137.8, 133.8, 132.5,
131.8, 130.5, 130.1, 130.1, 130.0, 129.9, 129.6, 128.5, 128.4, 128.3, 128.3, 126.9, 126.8, 126.6,
126.4, 126.2, 126.1, 126.0, 125.4, 125.1, 122.8, 99.7, 98.9, 56.3, 56.2, 35.8, 31.9, 31.1, 29.5, 29.4,
29.4, 29.3, 29.3, 29.3, 22.7, 21.7, 21.0, 20.9, 20.5, 20.4, 14.1. HRMS (ESI): m/z [M + H]+ calcd for
C62H76N6O4P + H: 969.6001; found: 969.6003.
(S)-1,1'-(2,2'-Bis(methoxymethoxy)-6,6'-dioctyl-[1,1'-binaphthalene]-3,3'-diyl)bis(4-(2,4,6-triiso-
propylphenyl)-1H-1,2,3-triazole) (5d)
Following the General Procedure C, subjection of 3,3’-diazido-MOM-BINOL 11 (1.36 g, 2.0 mmol,
1.0 eq.) and 2,4,6-triisopropylbenzene acetylene (1.37 g, 6.0 mmol, 3.0 eq.) with subsequent
purification by column chromatography using PE/EtOAc (10:1) as eluent gave the title compound
1
(1.33 g, 1.16 mmol, 58%) as a brown solid. Rf = 0.22 (10:1) (SiO2, PE/EtOAc). H-NMR (300 MHz,
CDCl3) δ[ppm]: 8.44 (d, J = 5.9 Hz, 2H), 8.19 (d, J = 1.5 Hz, 2H), 7.78 (s, 2H), 7.27 (d, J = 0.7 Hz,
2H), 7.17 (dd, J = 10.0, 0.8 Hz, 2H), 7.10 (s, 4H), 4.50 (d, J = 5.4 Hz, 2H), 4.38 (d, J = 5.2 Hz, 2H),
3.23 (s, 2H), 2.97 – 2.90 (m, 4H), 2.85 - 2.67 (m, 12H), 2.54 (s, 6H), 1.73 – 1.65 (m, 6H), 1.43 - 1.22
(m, 20H), 1.18 – 1.11 (m, 12H), 1.00 - 0.73 (m, 6H). 13C-NMR (100 MHz, CDCl3) δ[ppm]: 149.8,
148.7, 148.6, 145.5, 145.3, 141.5, 130.7, 130.6, 130.4, 129.7, 129.5, 128.6, 126.8, 126.7, 125.1,
125.0, 122.1, 120.7, 99.0, 60.4, 56.4, 56.0, 41.4, 36.1, 35.9, 34.5, 34.3, 34.1, 31.9, 31.6, 31.1, 30.6,
29.5, 29.3, 29.1, 27.7, 24.3, 24.2, 24.1, 24.0, 23.9, 23.8, 22.7, 22.6, 20.5, 19.5, 18.8, 14.3, 14.2,
14.1, 11.5. HRMS (ESI): m/z [M + H]+ calcd for C74H100N6O4 + H: 1137.7879; found: 1137.7878.
(S)-1,1'-(2,2'-Bis(methoxymethoxy)-6,6'-dioctyl-[1,1'-binaphthalene]-3,3'-diyl)bis(4-(adaman-
tyl)-1H-1,2,3-triazole) (5e)

Following the General Procedure C, subjection of 3,3’-diazido-MOM-BINOL 11 (0.64 g, 0.93 mmol,
1.0 eq.) and adamantyl acetylene (0.44 g, 2.79 mmol, 3.0 eq.) with subsequent purification by
column chromatography using PE/EtOAc (5:1) as eluent gave the title compound (0.43 g,
1
0.43 mmol, 46%) as a brown solid. Rf = 0.45 (5:1) (SiO2, PE/EtOAc). H-NMR (300 MHz, CDCl3)
δ[ppm]: 7.82 (d, J = 9.0 Hz, 2H), 7.58 (s, 2H), 7.48 (d, J = 9.0 Hz, 2H), 7.24 (d, J = 8.1 Hz, 2H), 7.03
(s, 4H), 5.00 (d, J = 6.7 Hz, 2H), 4.90 (d, J = 6.7 Hz, 2H), 3.09 (s, 6H), 2.72 - 2.61 (m, 4H), 2.09 –
2.02 (m, 4H), 1.79 – 1.74 (m, 10H), 1.65 – 1.61 (m, 20H), 1.21 (bs, 20H), 0.80 (s, 6H). HRMS (ESI):
m/z [M + H]+ calcd for C64H84N6O4 + H: 1001.6627; found: 1001.6637.
(S)-1,1'-2,2'-Bis(methoxymethoxy)-6,6'-dioctyl-[1,1'-binaphthalene]-3,3'-diyl)bis(4-(4-bromo-
2,6-diisopropylphenyl)-1H-1,2,3-triazole) (5f)
Following the General Procedure C, subjection of 3,3’-diazido-MOM-BINOL 11 (1.01 g, 1.5 mmol,
1.0 eq.) and 1-ethynyl-2-bromo-2,6-diisopropylbenzene (0.98 g, 3.7 mmol, 2.5 eq.) with subsequent
purification by column chromatography using PE/EtOAc (10:1) as eluent gave the title compound
1
(1.27 g, 1.05 mmol, 71%) as a brown solid. Rf = 0.51 (10:1) (SiO2, PE/EtOAc). H-NMR (300 MHz,
CDCl3) δ[ppm]: 8.53 (s, 2H), 8.32 (s, 2H), 7.70 (s, 4H), 7.37 - 7.12 (m, 6H), 4.52 (d, J = 5.8 Hz, 2H),
4.41 (d, J = 5.8 Hz, 2H), 3.61 – 3.51 (m, , 4H), 2.76 (dd, J = 15.2, 7.6 Hz, 4H), 2.58 (s, 6H), 1.75 –
1.62 (m, 4H), 1.35 – 1.31 (m, 24H), 1.29 – 1.18 (m, 20H), 0.87 (t, J = 6.5 Hz, 6H). 13C-NMR
(75 MHz, CDCl3) δ[ppm]: 148.6, 147.7, 145.7, 141.7, 132.2, 130.6, 130.3, 130.0, 129.5, 126.9,
126.8, 126.6, 126.1, 126.0, 122.1, 121.7, 99.7, 56.7, 35.9, 33.8, 31.9, 31.1, 29.5, 29.4, 29.3, 23.1,
22.7, 14.1. HRMS (ESI): m/z [M + H]+ calcd for C68H86Br2N6O4 + H: 1209.5150; found: 1209.5138.
(S)-1,1'-2,2'-Bis(methoxymethoxy)-(6,6'-didodecyl-[1,1'-binaphthalene]-3,3'-diyl)bis(4-
mesityl-1H-1,2,3-triazole) (5g)
Following the General Procedure C, subjection of 3,3’-diazido-MOM-BINOL 12 (1.72 g, 2.2 mmol,
1.0 eq.) and mesityl acetylene (0.95 g, 6.6 mmol, 3.0 eq.) with subsequent purification by column
chromatography using PE/EtOAc (20:1) as eluent gave the title compound (1.76 g, 1.8 mmol, 80%)
1
as a brown solid. Rf = 0.38 (20:1) (SiO2, PE/EtOAc). H-NMR (300 MHz, CDCl3) δ[ppm]: 7.82 (d,
J = 9.1 Hz, 2H), 7.58 (s, 2H), 7.48 (d, J = 9.0 Hz, 2H), 7.22 (s, 2H), 7.03 (s, 4H), 6.82 (s, 2H), 5.01
(d, J = 6.7 Hz, 2H), 4.90 (d, J = 6.7 Hz, 2H), 3.09 (s, 6H), 2.74 - 2.61 (m, 4H), 2.37 (s, 9H), 2.24 (s,
9H), 1.66 - 1.57 (m, 4H), 1.20 (bs, 36H), 0.89 - 0.77 (m, 6H). 13C-NMR (75 MHz, CDCl3) δ[ppm]:
152.3, 145.9, 145.6, 144.7, 141.0, 138.9, 138.2, 137.9, 137.8, 132.1, 130.7, 130.6, 130.4, 130.3,
129.8, 129.2, 128.8, 128.4, 127.9, 126.8, 126.2, 125.5, 119.4, 117.5, 99.0, 95.5, 56.6, 56.0, 55.8,
35.9, 31.9, 31.3, 31.2, 29.7, 29.7, 29.6, 29.6, 29.4, 22.7, 21.2, 20.8, 14.2. HRMS (ESI): m/z [M + H]+
calcd for C70H92N6O4 + H: 1081.7253; found: 1081.7245.
(S)-1,1'-(2,2'-Bis(methoxymethoxy)-6,6'-dioctadecyl-[1,1'-binaphthalene]-3,3'-diyl)bis(4-mesityl
-1H-1,2,3-triazole) (5h)

Following the General Procedure C, subjection of 3,3’-diazido-MOM-BINOL 13 (2.24 g, 2.3 mmol,
1.0 eq.) and mesityl acetylene (1.00 g, 6.9 mmol, 3.0 eq.) with subsequent purification by column
chromatography using PE/EtOAc (10:1) as eluent gave the title compound (1.89 g, 1.5 mmol, 66%)
1
as a brown solid. Rf = 0.42 (10:1) (SiO2, PE/EtOAc). H-NMR (300 MHz, CDCl3) δ[ppm]: 8.41 (s,
2H), 8.19 (s, 2H), 7.78 (s, 2H), 7.27 (s, 4H), 6.97 (s, 4H), 4.49 (d, J = 5.5 Hz, 2H), 4.38 (d,
J = 5.5 Hz, 2H), 2.83 - 2.70 (m, 4H), 2.54 (s, 6H), 2.33 (s, 6H), 2.20 (bs, 12H), 1.76 - 1.65 (m, 4H),
1.26 (bs, 60H), 0.88 (t, J = 6.9 Hz, 6H). 13C-NMR (75 MHz, CDCl3) δ[ppm]: 145.9, 145.4, 141.5,
138.3, 137.8, 132.0, 130.6, 130.3, 129.8, 128.5, 126.9, 126.8, 126.7, 126.2, 125.6, 125.0, 99.1,
56.5, 35.9, 32.0, 31.1, 29.8, 29.7, 29.6, 29.5, 29.4, 22.7, 21.2, 20.9, 14.2. HRMS (ESI): m/z [M + H]+
calcd for C82H116N6O4 + H: 1249.9131; found: 1249.9156.
General Procedure D: MOM-deprotection of BINOL derivatives
A stirring solution of MOM-protected BINOL derivative (1 eq.) in a 1:2 mixture of CH2Cl2/MeOH
(33 ml) was treated with 12 M aq. HCl (38 eq.). The reaction mixture was stirred for 12 h at 50 °C.
The solution was allowed to cool to room temperature, was neutralized with sat. aq. NaHCO3 and
extracted with CH2Cl2 (3 x 30 ml). The combined organic layers were dried over Na2SO4, filtered and
the solvent was removed under reduced pressure. The desired products were obtained by
precipitation (CH2Cl2-cyclohexane) and filtration.
(S)-3,3'-Bis(4-phenyl-1H-1,2,3-triazol-1-yl)-[1,1'-binaphthalene]-2,2'-diol (6a)[15a]
Following the General procedure D, the deprotection of triazolyl-MOM-BINOL 5a (0.97 g, 1.5 mmol,
1
1.0 eq.) gave the title compound (0.69 g, 1.2 mmol, 80%) as a brown solid. H-NMR (300 MHz,
DMSO-d6) δ[ppm]: 9.58 (s, 2H), 9.05 (s, 2H), 8.46 (s, 2H), 8.11 (d, J = 7.4 Hz, 2H), 8.02 - 7.97 (m,
4H), 7.55 - 7.34 (m, 10H), 7.06 (d, J = 8.2 Hz, 2H). The analytical data are in accordance with the
literature.
(S)-3,3'-Bis(4-mesityl-1H-1,2,3-triazol-1-yl)-[1,1'-binaphthalene]-2,2'-diol (6b)[15a]
Following the General procedure D, the deprotection of triazolyl-MOM-BINOL 5b (257.3 mg,
0.35 mmol, 1.0 eq.) gave the title compound (211.5 mg, 0.32 mmol, 91%) as a brown solid. 1H-NMR
(300 MHz, DMSO-d6) δ[ppm]: 9.31 (s, 2H), 8.53 - 8.50 (m, 2H), 8.12 -7.99 (m, 2H), 7.79 - 7.73 (m,
2H), 7.34 – 7.25 (m, 4H), 6.97 (s, 4H), 6.85 (s, 2H), 2.21 (s, 6H), 2.14 (bs, 12H). The analytical data
are in accordance with the literature.
(S)-3,3'-Bis(4-mesityl-1H-1,2,3-triazol-1-yl)-6,6'-dioctyl-[1,1'-binaphthalene]-2,2'-diol (6c)
Following the General procedure D, the deprotection of triazolyl-MOM-BINOL 5c (0.97 g, 1.0 mmol,
1
1.0 eq.) gave the title compound (0.88 g, 0.99 mmol, 99%) as a brown solid. H-NMR (400 MHz,
CDCl3) δ[ppm]: 8.38 - 7.95 (m, 4H), 7.74 - 7.56 (m, 2H), 7.29 - 7.08 (m, 4H), 7.01 - 6.79 (m, 4H),
2.88- 2.51 (m, 4H), 2.37 - 2.24 (m, 6H), 2.22 - 1.88 (m, 12H), 1.78 - 1.52 (m, 4H), 1.45 - 1.18 (m,

20H), 0.95 - 0.81 (m, 6H). 13C-NMR (100 MHz, CDCl3) δ[ppm]: 145.6, 144.7, 139.6, 138.5, 137.9,
131.9, 129.7, 128.6, 128.4, 128.3, 126.9, 126.3, 125.1, 124.8, 122.6, 120.4, 118.2, 35.9, 32.0, 31.5,
31.3, 29.6, 29.5, 29.4, 22.8, 21.2, 20.8, 20.3, 19.7, 14.2. HRMS (ESI): m/z [M - H]- calcd for
C58H67N6O2 - H: 879.5331; found: 879.5333.
(S)-6,6'-Dioctyl-3,3'-bis(4-(2,4,6-triisopropylphenyl)-1H-1,2,3-triazol-1-yl)-[1,1'-binaphthalene]-
2,2'-diol (6d)
Following the General procedure D, the deprotection of triazolyl-MOM-BINOL 5d (1.68 g, 1.5 mmol,
1
1.0 eq.) gave the title compound (1.43 g, 1.36 mmol, 91%) as a brown solid. H-NMR (300 MHz,
CDCl3) δ[ppm]: 9.50 (s, 2H), 8.26 (s, 2H), 8.17 (s, 2H), 7.74 (s, 2H), 7.23 (s, 4H), 7.14 (s, 4H), 2.97
(dd, J = 13.7, 6.9 Hz, 3H), 2.83 - 2.60 (m, 14H), 1.73 – 1.64 (m, 8H), 1.27 (bs, 20H), 1.21 – 1.15 (m,
34H), 0.88 (t, J = 6.4 Hz, 6H). 13C-NMR (100 MHz, CDCl3) δ[ppm]: 152.2, 150.3, 150.0, 148.8,
147.6, 145.7, 145.4, 144.6, 144.4, 139.8, 138.3, 132.1, 131.8, 130.5, 129.9, 129.5, 129.4, 128.8,
128.7, 128.6, 128.5, 128.3, 128.1, 127.0, 126.9, 126.6, 125.4, 125.0, 124.9, 124.8, 124.5, 124.4,
123.6, 122.3, 121.7, 121.6, 120.9, 120.8, 119.7, 118.5, 118.1, 117.1, 112.2, 53.5, 35.9, 34.6, 34.4,
32.0, 31.5, 31.3, 30.8, 30.7, 30.0, 29.6, 29.5, 29.4, 29.3, 24.3, 24.2, 24.1, 23.9, 22.8, 21.7, 14.2.
HRMS (ESI): m/z [M - H]+ calcd for C70H92N6O2 + H: 1049.7355; found: 1049.7351.
(S)-6,6'-Dioctyl-3,3'-bis(4-(adamantyl)-1H-1,2,3-triazol-1-yl)-[1,1'-binaphthalene]-2,2'-diol (6e)
Following the General procedure D, the deprotection of triazolyl-MOM-BINOL 5e (0.43 g, 0.43 mmol,
1
1.0 eq.) gave the title compound (0.37 g, 0.40 mmol, 93%) as a brown solid. H-NMR (300 MHz,
CDCl3) δ[ppm]: 9.57 (s, 2H), 8.05 (s, 2H), 8.02 (s, 2H), 7.67 (s, 2H), 7.18 - 7.13 (m, 4H), 2.71 (dd,
J = 14.6, 6.5 Hz, 6H), 2.07 (s, 15H), 1.89 (d, J = 2.9 Hz, 2H), 1.82 (bs, 15H), 1.25 (bs, 20H),
0.92 - 0.84 (m, 6H). HRMS (ESI): m/z [M - H]+ calcd for C60H76N6O2 + H: 913.6103; found: 913.6105.
(S)-3,3'-Bis(4-(4-bromo-2,6-diisopropylphenyl)-1H-1,2,3-triazol-1-yl)-6,6'-dioctyl-[1,1'-
binaphthalene]-2,2'-diol (6f)
Following the General procedure D, the deprotection of triazolyl-MOM-BINOL 5f (1.27 g, 1.05 mmol,
1
1.0 eq.) gave the title compound (0.82 g, 0.73 mmol, 70%) as a brown solid. H-NMR (300 MHz,
CDCl3) δ[ppm]: 8.94 (s, 2H), 8.58 (s, 2H), 8.24 (s, 2H), 7.75 - 7.60 (m, 4H), 7.25 - 7.08 (m, 4H),
3.63 – 3.53 (m, 4H), 2.76 – 2.70 (m, , 4H), 1.77 - 1.62 (m, 4H), 1.36 – 1.32 (m, 24H), 1.31 – 1.22 (m,
20H), 0.87 (t, J = 5.8 Hz, 6H). 13C-NMR (100 MHz, CDCl3) δ[ppm]: 148.7, 147.7, 144.4, 139.9,
131.6, 129.9, 128.9, 128.2, 127.1, 126.8, 124.7, 121.9, 121.8, 120.0, 119.2, 118.0, 35.8, 33.7, 31.9,
31.1, 29.5, 29.3, 29.2, 23.0, 22.7, 14.1. HRMS (ESI): m/z [M - H]+ calcd for C64H78Br2N6O2 + H:
1121.4626; found: 1121.4615.
(S)-3,3'-Bis(4-mesityl-1H-1,2,3-triazol-1-yl)-6,6'-didodecyl-[1,1'-binaphthalene]-2,2'-diol (6g)

Following the General procedure D, the deprotection of triazolyl-MOM-BINOL 5g (1.76 g, 1.8 mmol,
1
1.0 eq.) gave the title compound (1.26 g, 1.26 mmol, 70%) as a brown solid. H-NMR (300 MHz,
CDCl3) δ[ppm]: 8.32 – 8.18 (m, 2H), 7.95 - 7.59 (m, 4H), 7.34 (dd, J = 8.8, 2.0 Hz, 2H), 7.25 - 7.06
(m, 4H), 7.00 (d, J = 2.1 Hz, 2H), 2.77 – 2.70 (m, 4H), 2.36 (s, 6H), 2.20 (s, 12H), 1.78 - 1.58 (m,
4H), 1.42 - 1.19 (m, 36H), 0.91 - 0.81 (m, 6H). 13C-NMR (100 MHz, CDCl3) δ[ppm]: 145.8, 144.7,
144.5, 140.1, 139.8, 138.7, 138.6, 138.5, 138.4, 137.9, 131.7, 131.6, 130.8, 130.6, 130.1, 129.8,
129.6, 129.5, 129.0, 128.8, 128.6, 128.5, 128.2, 127.9, 126.9, 126.3, 126.1, 125.0, 124.7, 124.2,
122.8, 121.3, 118.4, 117.8, 117.6, 116.1, 112.2, 110.9, 35.8, 32.0, 31.5, 31.3, 29.8, 29.7, 29.6, 29.5,
29.4, 22.7, 21.2, 20.8, 14.2. HRMS (ESI): m/z [M - H]+ calcd for C66H84N6O2 + H: 993.6729; found:
993.6719.
(S)-3,3'-Bis(4-mesityl-1H-1,2,3-triazol-1-yl)-6,6'-dioctadecyl-[1,1'-binaphthalene]-2,2'-diol (6h)
Following the General procedure D, the deprotection of triazolyl-MOM-BINOL 5h (1.89 g, 1.5 mmol,
1
1.0 eq.) gave the title compound (1.48 g, 1.27 mmol, 85%) as a brown solid. H-NMR (300 MHz,
CDCl3) δ[ppm]: 8.24 (s, 2H), 8.16 (s, 2H), 7.72 (s, 2H), 7.21 (s, 4H), 7.00 (s, 4H), 2.87 - 2.63 (m,
4H), 2.35 (s, 6H), 2.20 (bs, 12H), 1.76 - 1.57 (m, 4H), 1.25 (bs, 60H), 0.88 (t, J = 6.7 Hz, 6H).
13C-NMR (100 MHz, CDCl3) δ[ppm]: 145.9, 144.5, 139.8, 138.7, 137.9, 131.6, 129.8, 128.6, 128.1,
126.7, 126.1, 124.7, 121.9, 119.5, 118.4, 35.9, 32.0, 31.2, 29.8, 29.7, 29.6, 29.4, 22.7, 21.2, 20.8,
14.2. HRMS (ESI): m/z [M - H]+ calcd for C78H108N6O2 + H: 1161.8607; found: 1161.8619.
General procedure E: Synthesis of phosphoric acids[13]
To a stirring solution of triazolyl diol (1 eq.) in pyridine (0.1 M) was added phosphoryl chloride (4 eq.)
dropwise under an atmosphere of N2. The reaction mixture was heated to 95 °C. Upon complete
consumption of the starting material, as judged by TLC, the reaction mixture was allowed to cool to
room temperature. H2O (1.0 M) was added dropwise at 0 °C and the mixture was again stirred at
95 °C. Upon complete consumption of the starting material, as judged by TLC, the reaction mixture
was allowed to cool to room temperature and the mixture was diluted with CH2Cl2 (10 ml) and 1.0 M
HCl (5 ml). The aqueous layer was separated with a Whatman© phase separator. The organic layer
was dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The desired
products were obtained by column chromatography.
(S)-4-Hydroxy-2,6-bis(4-phenyl-1H-1,2,3-triazol-1-yl)dinaphtho[2,1-d:1',2'-f]-[1,3,2]dioxaphos-
phepine 4-oxide (1a)
Following the General Procedure E, subjection of triazolyl diol 6a (0.57 g, 1.0 mmol, 1.0 eq.) and
phosphorylchloride (0.61 g, 4.0 mmol, 4.0 eq.) with subsequent purification by column
chromatography using CH2Cl2/MeOH (50:1) as eluent gave the title compound (0.49 g, 0.77 mmol,
1
77%) as a brown solid. Rf = 0.33 (50:1) (SiO2, CH2Cl2/MeOH). H-NMR (400 MHz, DMSO-d6)

δ[ppm]: 9.74 (s, 2H), 8.69 (s, 2H), 8.15 - 7.99 (m, 2H), 7.95 (d, J = 7.3 Hz, 4H), 7.57 - 7.44 (m, 8H),
7.44 - 7.33 (m, 2H), 7.28 (d, J = 5.2 Hz, 2H). 13C-NMR (100 MHz, DMSO-d6) δ[ppm]: 154.0, 147.2,
146.5, 146.4, 141.7, 141.6, 133.8, 131.6, 130.5, 130.5, 129.9, 129.2, 129.1, 129.0, 128.9, 128.9,
128.7, 128.2, 128.1, 127.7, 127.3, 127.2, 126.5, 126.1, 125.4, 125.3, 124.2, 124.2, 124.1, 123.5,
123.3, 123.2, 123.2, 116.6. 31P-NMR (162 MHz, DMSO-d6) δ[ppm]: 5.19. HRMS (ESI): m/z [M + H]+
calcd for C36H23N6O4P + H: 635.1591; found: 635.1593.
(S)-4-Hydroxy-2,6-bis(4-mesityl-1H-1,2,3-triazol-1-yl)dinaphtho[2,1-d:1',2'-f]-[1,3,2]dioxaphos-
phepine 4-oxide (1b)
Following the General Procedure E, subjection of triazolyl diol 6b (206.8 mg, 0.32 mmol, 1.0 eq.)
and phosphorylchloride (196.3 mg, 1.30 mmol, 4.0 eq.) with subsequent purification by column
chromatography using CH2Cl2/MeOH (20:1) as eluent gave the title compound (63.1 mg, 0.09 mmol,
1
27%) as a brown solid. Rf = 0.29 (20:1) (SiO2, CH2Cl2/MeOH). H-NMR (400 MHz, CDCl3) δ[ppm]:
8.92 - 6.54 (bm, 28H) (should be 17H), 1.38 - 1.11 (bm, 12H), 0.92 - 0.77 (bm, 6H). 13C-NMR
(100 MHz, CDCl3) δ[ppm]: no signals could be recorded after 7000 scans. 31P-NMR (162 MHz,
CDCl3) δ[ppm]: 2.72. HRMS (ESI): m/z [M + H]+ calcd for C42H35N6O4P + H: 719.2530; found:
719.2536.
(4R,11bS)-4-Hydroxy-2,6-bis(4-mesityl-1H-1,2,3-triazol-1-yl)-9,14-dioctyldinaphtho[2,1-d:1',2'-f]
-[1,3,2]dioxaphosphepine 4-oxide (1c)
Following the General Procedure E, subjection of triazolyl diol 6c (876.0 mg, 0.99 mmol, 1.0 eq.)
and phosphorylchloride (607.0 mg, 3.96 mmol, 4.0 eq.) with subsequent purification by column
chromatography using CH2Cl2/MeOH (20:1) as eluent gave the title compound (788.9 mg,
1
0.83 mmol, 84%) as a brown solid. Rf = 0.33 (20:1) (SiO2, CH2Cl2/MeOH). H-NMR (400 MHz,
CDCl3) δ[ppm]: 8.31 - 7.90 (m, 3H), 7.79 - 7.49 (m, 2H), 7.42 - 7.10 (m, 3H), 7.06 - 6.62 (m, 6H),
2.89 - 2.67 (m, 4H), 2.64 (s, 3H), 2.35 (s, 3H), 2.20 (s, 6H), 1.92 (s, 6H), 1.75 - 1.52 (m, 4H), 1.29
(bs, 20H), 0.89 (t, J = 6.4 Hz, 6H). 13C-NMR (100 MHz, CDCl3) δ[ppm]: 145.9, 144.5, 140.8, 139.7,
138.6, 137.8, 137.7, 131.6, 130.3, 129.7, 128.5, 128.4, 128.1, 126.7, 124.7, 123.4, 121.9, 119.5,
118.4, 35.8, 35.7, 31.9, 31.2, 30.9, 29.5, 29.4, 29.3, 29.3, 29.2, 22.7, 22.6, 21.1, 21.0, 20.8, 20.6,
31
14.1, 14.1. P-NMR (162 MHz, CDCl3) δ[ppm]: 0.99. HRMS (ESI): m/z [M + H]+ calcd for
C58H66N6O4P + H: 943.5034; found: 943.5029.
(4R,11bS)-4-hydroxy-9,14-dioctyl-2,6-bis(4-(2,4,6-triisopropylphenyl)-1H-1,2,3-triazol-1-yl)
dinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepine 4-oxide (1d)
Following the General Procedure E, subjection of triazolyl diol 6d (876.0 mg, 0.99 mmol, 1.0 eq.)
and phosphorylchloride (607.0 mg, 3.96 mmol, 4.0 eq.) with subsequent purification by column
chromatography using CH2Cl2/MeOH (20:1) as eluent gave the title compound (788.9 mg,
1
0.83 mmol, 84%) as a brown solid. Rf = 0.33 (20:1) (SiO2, CH2Cl2/MeOH). H-NMR (300 MHz,

CDCl3) δ[ppm]: 8.59 (s, 2H), 8.27 (s, 2H), 7.69 (s, 2H), 7.20 (t, J = 7.3 Hz, 4H), 7.03 (s, 4H),
2.92 (dt, J = 13.7, 6.9 Hz, 2H), 2.79 – 2.68 (m, 8H), 1.67 (s, 4H), 1.41 – 1.27 (m, 32H),
1.08 – 1.03 (m, 22H), 0.91 – 0.86 (m, 8H). 13C-NMR (75 MHz, CDCl3) δ[ppm]: 149.6, 148.8,
145.0, 141.2, 130.5, 129.3, 127.0, 126.7, 120.6, 35.7, 34.5, 31.9, 31.1, 30.5, 29.5, 29.4,
29.3, 24.2, 24.1, 22.7, 14.2. 31P-NMR (121 MHz, CDCl3) δ[ppm]: 3.11. HRMS (ESI): m/z [M - H]+
calcd for C70H91N6O4P + H: 1111.6912; found: 1111.6916.
(4R,11bS)-4-hydroxy-9,14-dioctyl-2,6-bis(4-(adamantyl)-1H-1,2,3-triazol-1-yl)dinaphtho
[2,1-d:1',2'-f][1,3,2]dioxaphosphepine 4-oxide (1e)
Following the General Procedure E, subjection of triazolyl diol 6e (366.7 mg, 0.4 mmol, 1.0 eq.) and
phosphorylchloride (245.3 mg, 1.6 mmol, 4.0 eq.) with subsequent purification by column
chromatography using CH2Cl2/MeOH (20:1) as eluent gave the title compound (320.3 mg,
0.33 mmol, 83%) as a brown solid. Rf = 0.5 (20:1) (SiO2, CH2Cl2/MeOH). 1H-NMR (300 MHz, CDCl3)
δ[ppm]: 8.39 - 7.82 (m, 4H), 7.61 – 7.55 (m, 2H), 7.16 - 6.81 (m, 4H), 2.67 (t, J = 7.5 Hz, 4H),
2.20 - 1.96 (m, 6H), 1.91 – 1.52 (m, 22H), 1.40 - 1.07 (m, 26H), 0.82 (dd, J = 7.7, 5.3 Hz,
6H). 13C-NMR (100 MHz, CDCl3) δ[ppm]: 158.0, 144.6, 139.4, 131.5, 130.4, 129.5, 129.1, 128.0,
126.6, 124.7, 118.6, 42.7, 42.4, 42.1, 36.6, 36.5, 36.3, 35.8, 32.8, 31.9, 31.2, 29.7, 29.5, 29.4, 29.4,
29.3, 28.4, 28.3, 27.9, 22.7, 14.2. 31P-NMR (162 MHz, CDCl3) δ[ppm]: 3.34. HRMS (ESI): m/z
[M - H]+ calcd for C60H75N6O4P + H: 975.5660; found: 975.5663.
(4R,11bS)-2,6-Bis(4-(4-bromo-2,6-diisopropylphenyl)-1H-1,2,3-triazol-1-yl)-4-hydroxy-
9,14-dioctyldinaphtho[2,1-d:1',2'-f][1,3,2]dioxaphosphepine 4-oxide (1f)
Following the General Procedure E, subjection of triazolyl diol 6f (821.3 mg, 0.73 mmol, 1.0 eq.) and
phosphorylchloride (447.7 mg, 2.92 mmol, 4.0 eq.) with subsequent purification by column
chromatography using CH2Cl2/MeOH (20:1) as eluent gave the title compound (711.3 mg, 0.6 mmol,
1
82%) as a brown solid. Rf = 0.52 (20:1) (SiO2, CH2Cl2/MeOH). H-NMR (300 MHz, CDCl3) δ[ppm]:
8.61 (s, 2H), 8.19 (s, 2H), 7.74 - 7.28 (m, 6H), 7.22 - 6.97 (m, 4H), 3.78 - 3.44 (m, 4H), 2.79 - 2.49
(m, 4H), 1.63 (s, 4H), 1.44 - 1.14 (m, 44H), 0.90 (t, J = 6.5 Hz, 6H). 13C-NMR (75 MHz, CDCl3)
δ[ppm]: 148.5, 148.4, 147.4, 144.6, 139.7, 131.7, 129.9, 128.8, 128.2, 126.9, 126.8, 124.9, 124.5,
121.8, 120.6, 119.7, 117.7, 35.8, 33.7, 32.0, 31.2, 29.5, 29.4, 29.3, 23.0, 22.7, 14.2. 31P-NMR
(121 MHz, CDCl3) δ[ppm]: 3.25. HRMS (ESI): m/z [M - H]+ calcd for C64H77Br2N6O4P + H:
1183.4183; found: 1183.4168.
(4R,11bS)-2,6-Bis(4-mesityl-1H-1,2,3-triazol-1-yl)-4-hydroxy--9,14-didodecyldinaphtho
[2,1-d:1',2'-f][1,3,2]dioxaphosphepine 4-oxide (1g)
Following the General Procedure E, subjection of triazolyl diol 6g (1.26 g, 1.26 mmol, 1.0 eq.) and
phosphorylchloride (0.77 g, 5.04 mmol, 4.0 eq.) with subsequent purification by column

chromatography using CH2Cl2/MeOH (20:1) as eluent gave the title compound (185.9 mg,
1
0.18 mmol, 14%) as a brown solid. Rf = 0.14 (20:1) (SiO2, CH2Cl2/MeOH). H-NMR (300 MHz,
CDCl3) δ[ppm]: 8.33 - 8.16 (m, 4H), 7.63 (s, 2H), 7.08 (s, 4H), 6.76 (s, 4H), 2.70 (s, 4H), 2.26 (s,
6H), 2.02 (s, 12H), 1.65 (s, 4H), 1.29 (bs, 36H), 0.90 (t, J = 6.6 Hz, 6H). 13C-NMR (75 MHz, CDCl3)
δ[ppm]: 145.1, 141.1, 141.0, 140.8, 137.7, 137.6, 130.4, 130.2, 129.0, 128.8, 128.3, 126.9, 126.6,
126.5, 126.4, 125.8, 123.5, 35.6, 31.9, 30.9, 29.7, 29.6, 29.5, 29.4, 29.3, 22.6, 21.0, 20.7, 14.0.
31P-NMR (121 MHz, CDCl3) δ[ppm]: 2.37. HRMS (ESI): m/z [M - H]+ calcd for C66H83N6O4P + H:
1055.6286; found: 1055.6273.
(4R,11bS)-2,6-Bis(4-mesityl-1H-1,2,3-triazol-1-yl)-4-hydroxy-9,14-dioctadecyldinaphtho
[2,1-d:1',2'-f][1,3,2]dioxaphosphepine 4-oxide (1h)
Following the General Procedure E, subjection of triazolyl diol 6h (1.48 g, 1.27 mmol, 1.0 eq.) and
phosphorylchloride (0.78 g, 5.08 mmol, 4.0 eq.) with subsequent purification by column
chromatography using CH2Cl2/MeOH (20:1) as eluent gave the title compound (750.6 mg,
1
0.61 mmol, 48%) as a brown solid. Rf = 0.49 (20:1) (SiO2, CH2Cl2/MeOH). H-NMR (300 MHz,
CDCl3) δ[ppm]: 8.11 (s, 4H), 7.58 (s, 2H), 7.05 (s, 4H), 6.71 (s, 4H), 2.69 (s, 4H), 2.27 (s, 6H), 1.96
(s, 12H), 1.65 (s, 4H), 1.31 (bs, 60H), 0.91 (t, J = 6.7 Hz, 6H). 13C-NMR (75 MHz, CDCl3) δ[ppm]:
148.4, 144.9, 140.9, 140.6, 137.5, 137.3, 136.1, 130.3, 130.0, 128.8, 128.5, 128.3, 126.8, 126.4,
126.2, 125.8, 123.2, 35.6, 31.8, 30.8, 29.6, 29.5, 29.4, 29.2, 22.6, 20.9, 20.6, 14.0. 31P-NMR
(121 MHz, CDCl3) δ[ppm]: 1.69. HRMS (ESI): m/z [M - H]+ calcd for C78H107N6O4P + H: 1223.8164;
found: 1223.8157.
N-((4S,11bS)-2,6-Bis(4-mesityl-1H-1,2,3-triazol-1-yl)-9,14-dioctyl-4-oxidodinaphtho[2,1-d:1',2'-f]
[1,3,2]dioxaphosphepin-4-yl)-1,1,1-trifluoromethanesulfonamide (1c#)[27]
To a solution of BINOL (1.2 g, 1.4 mmol, 1.0 eq.) in CH2Cl2 (7.0 mL) were added Et3N (1.3 mL,
9.6 mmol, 6.9 eq.), POCl3 (0.16 mL, 1.7 mmol, 1.2 eq.) and DMAP (334 mg, 2.7 mmol, 2.0 eq.) at
0 °C. After being stirred for 1 hour at room temperature, EtCN (7.0 mL) and TfNH2 (0.5 g, 3.4 mmol,
2.4 eq.) were added at room temperature. The reaction mixture was stirred at 100 °C and was
allowed to cool to room temperature after 12 hours. The solution was quenched with H2O (15 ml)
and extracted with Et2O (2 x 15 ml). The combined organic layers were washed with sat. aq.
NaHCO3 (10 ml), 4M HCl (2 x 10 ml), dried over Na2SO4, filtered and the solvent was removed under
reduced pressure. Purification of the crude product by column chromatography (PE/EA 4:1) gave
the title compound (105.3 mg, 0.01 mmol, 7%) as a brown solid [along with the PA 1c (330.1 mg,
1
0.35 mmol, 25%)]. H-NMR (300 MHz, CDCl3) δ[ppm]: 8.35 (s, 1H), 8.17 (s, 1H), 7.92 – 7.86 (m,
2H), 7.77 (d, J = 5.9 Hz, 2H), 7.30 (t, J = 9.3 Hz, 2H), 7.23 (s, 2H), 6.92 (s, 2H), 6.61 (s, 2H), 2.80 –
2.74 (m, 4H), 2.31 (s, 3H), 2.10 (s, 9H), 2.00 (s, 6H), 1.68 (s, 4H), 1.40 - 1.17 (m, 20H), 0.93 - 0.81
(m, 6H). 13C-NMR (75 MHz, CDCl3) δ[ppm]: 145.1, 140.9, 137.8, 130.5, 130.3, 129.1, 128.4, 126.9,

126.7, 126.4, 126.3, 123.6, 35.7, 31.9, 31.0, 29.5, 29.3, 22.7, 21.1, 20.7, 14.2. 31P-NMR (121 MHz,
CDCl3) δ[ppm]: 3.55. HRMS (ESI): m/z [M + H]+ calcd for C59H68F3N7O5PS + H: 1074.4687; found:
1074.4680.
General Procedure for the Catalytic Reaction:
The PA catalyst 1c (18.9 mg, 0.02 mmol, 10 mol%) and Na3PO4 (50.9 mg, 0.48 mmol, 2.4 eq.) were
dissolved in dry Et2O (8 ml) and stirred for 30 min until the catalyst was completely dissolved.
-
Dihydroisoquinoline benzamide 2 (0.2 mmol, 1.0 eq.) and oxidant AcNHT+BF4 (132.0 mg,
0.44 mmol, 2.2 eq.) were added and the reaction mixture was stirred vigorously for 24 h at room
temperature. After this time, the reaction mixture was diluted with sat. aq. Na2SO3 (4 ml) and the
contents were shaken. The mixture was extracted with EtOAc (3 x 4 ml) and the combined organic
layers were dried over Na2SO4, filtered and the solvent was removed under reduced pressure. The
desired product was purified by column chromatography with a PE/EtOAc mixture as eluent.
5-Benzyl-4b,5,12,13-tetrahydro-6H-isoquinolino[2,1-a]quinazolin-6-one (3a)[13,16c]
Following the General Catalytic Procedure, the reaction of benzamide 2a (68.5 mg, 0.20 mmol)
provided, after column chromatography (PE/EtOAc, 4:1), the desired product (66.9 mg, 0.19 mmol,
99%, 78:22 e.r.) as a white solid. The scale-up reaction of 2a (342.5 mg, 1.0 mmol) and 1c (94.3
mg, 0.1 mmol, 10 mol%) in 40 mL Et2O provided 3a (324.9 mg, 95%) with a 70:30 e.r., and the
recrystallization from CH2Cl2/hexane led to the product in 92:8 e.r (130.0 mg, 40% of
1
recrystallization). Rf = 0.35 (4:1) (SiO2, PE/EtOAc). H-NMR (300 MHz, CDCl3) δ 7.94 (dd, J = 7.7,
1.3 Hz, 1H), 7.34 – 7.22 (m, 7H), 7.19 – 7.09 (m, 2H), 7.02 – 6.96 (m, 1H), 6.83 (dd, J = 13.6, 7.7
Hz, 2H), 5.70 (bd, J = 14.5 Hz, 1H), 5.64 (s, 1H), 4.34 (d, J = 15.3 Hz, 1H), 3.97 (dd, J = 14.2, 5.1
Hz, 1H), 3.47 (ddd, J = 14.2, 11.1, 5.7 Hz, 1H), 3.16 – 2.98 (m, 1H), 2.67 (dd, J = 17.0, 3.8 Hz, 1H).
13C-NMR (75 MHz, CDCl3) δ 163.5, 147.5, 137.3, 134.9, 133.5, 129.6, 129.3, 128.7, 128.3, 127.7,
127.6, 126.3, 126.0, 119.5, 118.6, 113.7, 71.8, 49.8, 44.7, 24.6. HRMS (ESI): m/z [M + H]+ calcd for
C23H20N2 + H: 341.1648; found: 341.1655. HPLC (Chiralpak IC column, 75:25 hexanes/isopropanol,
1 ml/min); tr = 20.9 (minor), 25.0 (major) min.
5-(4-Chlorobenzyl)-4b,5,12,13-tetrahydro-6H-isoquinolino[2,1-a]quinazolin-6-one (3b)
Following the General Catalytic Procedure, the reaction of benzamide 2b (40.2 mg, 0.10 mmol,
1.0 eq.) provided, after column chromatography (CH2Cl2), the desired product (30.0 mg, 0.08 mmol,
80%, 72:28 e.r.) as a white solid. Rf = 0.49 (SiO2, CH2Cl2). 1H-NMR (300 MHz, CDCl3) δ[ppm]: 7.96
(dd, J = 7.7, 1.5 Hz, 1H), 7.36 (ddd, J = 8.7, 7.3, 1.6 Hz, 1H), 7.28 – 7.14 (m, 8H), 7.06 – 7.01 (m,
1H), 6.93 – 6.83 (m, 2H), 5.65 (s, 1H), 5.55 (bs, 1H), 4.37 (d, J = 15.5 Hz, 1H), 4.04 – 3.90 (m, 1H),
3.50 (ddd, J = 14.1, 10.9, 5.7 Hz, 1H), 3.16 – 2.96 (m, 1H), 2.73 (ddd, J = 16.9, 5.4, 2.4 Hz, 1H).
13C-NMR (75MHz, CDCl3) δ[ppm]: 163.7, 147.7, 136.0, 135.0, 133.6, 133.3, 132.4, 129.6, 129.4,

129.1, 128.8, 128.7, 128.5, 126.4, 126.2, 119.7, 114.0, 71.9, 48.9, 44.7, 24.9. HRMS (ESI): m/z
[M + H]+ calcd for C23H20ClN2O + H: 375.1259; found: 375.1265. HPLC (Chiralpak IC column, 75:25
hexanes/isopropanol, 1 ml/min); tr = 16.0 (minor), 22.0 (major) min.
5-(3,4-Dimethoxybenzyl)-4b,5,12,13-tetrahydro-6H-isoquinolino[2,1-a]quinazolin-6-one (3c)[16c]
Following the General Catalytic Procedure, the reaction of benzamide 2c (37.7 mg, 0.100 mmol,
1.0 eq.) provided, after column chromatography (PE/EtOAc, 4:1  2:1), the desired product
(32.4 mg, 0.081 mmol, 81%, 71:29 e.r.) as a pale yellow solid. Rf = 0.05 (4:1) (SiO2, PE/EtOAc). 1H-
NMR (300 MHz, CDCl3) δ[ppm]: 7.95 (dd, J = 7.7, 1.5 Hz, 1H), 7.33 (ddd, J = 8.7, 7.3, 1.6 Hz, 1H),
7.29 – 7.24 (m, 2H), 7.22 – 7.12 (m, 2H), 7.05 – 6.98 (m, 1H), 6.91 – 6.73 (m, 5H), 5.65 (s, 2H), 4.31
(d, J = 15.1 Hz, 1H), 4.06 – 3.93 (m, 1H), 3.50 (ddd, J = 14.2, 11.0, 5.8 Hz, 1H), 3.19 – 3.03 (m, 1H),
2.71 (dd, J = 17.0, 3.5 Hz, 1H). 13C-NMR (75 MHz, CDCl3) δ[ppm]: 163.4, 149.1, 148.4, 147.4,
134.8, 133.4, 129.7, 129.5, 129.2, 128.2, 126.2, 126.0, 120.2, 119.4, 113.7, 111.0, 111.0, 71.3,
68.0, 55.9, 44.6, 25.6. HRMS (ESI): m/z [M + H]+ calcd for C25H25N2O3 + H: 401.1860; found:
401.1868. HPLC (Chiralpak IA column, 80:20 hexanes/isopropanol, 1 ml/min); tr = 27.8 (major), 32.5
(minor) min.
5-((S)-1-Phenylethyl)-4b,5,12,13-tetrahydro-6H-isoquinolino[2,1-a]quinazolin-6-one (3d)
Following the General Catalytic Procedure, the reaction of benzamide 2d (35.6 mg, 0.100 mmol,
1.0 eq.) provided, after column chromatography (PE/EtOAc, 4:1), the desired product (28.0 mg,
0.079 mmol, 79%, 68:32 d.r.) as a white solid. Rf = 0.42 (4:1) (SiO2, PE/EtOAc). 1H-NMR (300 MHz,
CDCl3) δ[ppm]: 7.86 (d, J = 7.8 Hz, 1H major + 1H minor), 7.57 (d, J = 7.4 Hz, 1H major + 1H
minor), 7.45 (d, J = 7.5 Hz, 1H major + 1H minor), 7.42 – 7.22 (m, 5H major + 5H minor), 7.16 – 7.07
(m, 1H major + 1H minor), 7.05 – 6.66 (m, 3H major + 5H minor), 6.48 (d, J = 7.7 Hz, 1H major),
6.17 (s, 1H minor), 6.05 (s, 1H major), 5.73 (s, 1H major), 5.54 (s, 1H minor), 4.21 (dd, J = 14.4, 7.3
Hz, 1H major), 4.15 – 4.04 (m, 1H minor), 3.83 – 3.66 (m, 1H major), 3.56 – 3.42 (m, 1H minor),
3.30 – 3.10 (m, 1H major + 1H minor), 2.81 – 2.64 (m, 1H major + 1H minor), 1.81 (d, J = 7.1 Hz, 3H
major), 1.75 (d, J = 7.3 Hz, 3H, minor). 13C-NMR (75 MHz, CDCl3) δ[ppm]: 163.8, 147.3, 142.4,
133.4, 133.3, 129.7, 129.6, 129.2, 128.9, 128.8, 128.6, 128.5, 128.0, 127.5, 127.0, 126.4, 126.0,
125.5, 119.4, 119.0, 113.2, 69.3, 54.4, 53.3, 45.1, 44.7, 23.9, 18.9. HRMS (ESI): m/z [M + H]+ calcd
for C24H22N2O + H: 355.1805; found: 355.1810. HPLC (Chiralpak IA column, 85:15
hexanes/isopropanol, 1 ml/min); tr = 11.5 (minor), 16.3 (major) min.
4b,5,12,13-Tetrahydro-6H-isoquinolino[2,1-a]quinazolin-6-one (3e)[16a,b]
Following the General Catalytic Procedure, the reaction of benzamide 2e (25.2 mg, 0.100 mmol,
1.0 eq.) provided, after column chromatography (PE/EtOAc, 3:1), the desired product (17.1 mg,
0.041 mmol, 41%, 60:40 e.r.) as a white solid. Rf = 0.07 (3:1) (SiO2, PE/EtOAc). 1H-NMR (300 MHz,
CDCl3) δ[ppm]: 8.04 (dd, J = 7.9, 1.6 Hz, 1H), 7.49 (ddd, J = 8.4, 7.4, 1.7 Hz, 1H), 7.36 – 7.29 (m,

3H), 7.25 – 7.20 (m, 1H), 7.06 – 7.00 (m, 1H), 6.07 (bs, 1H), 5.73 (s, 1H), 3.92 – 3.84 (m, 1H), 3.29
– 3.19 (m, 1H), 3.17 – 3.11 (m, 1H), 3.04 – 2.94 (m, 1H). The analytical data are in accordance with
the literature. HPLC (Chiralpak IC column, 75:25 hexanes/isopropanol, 1 ml/min); tr = 18.0 (major),
20.2 (minor) min.
5-Cyclohexyl-4b,5,12,13-tetrahydro-6H-isoquinolino[2,1-a]quinazolin-6-one (3f)[13,16c]
Following the General Catalytic Procedure, the reaction of N-alkyl benzamide 2f (33.4 mg,
0.100 mmol, 1.0 eq.) provided, after column chromatography (CH2Cl2), the desired product (7.6 mg,
1
0.023 mmol, 23%, 59:41 e.r.) as a white solid. Rf = 0.28 (4:1) (SiO2, CH2Cl2). H-NMR (300 MHz,
CDCl3) δ[ppm]: 7.83 (dd, J = 7.7, 1.6 Hz, 1H), 7.37 – 7.32 (m, 1H), 7.29 – 7.22 (m, 2H), 7.15 – 7.04
(m, 2H), 7.01 – 6.94 (m, 1H), 6.85 (d, J = 8.2 Hz, 1H), 6.81 – 6.71 (m, 1H), 5.65 (s, 1H), 4.66 (bs,
1H), 4.22 (dd, J = 14.8, 7.1 Hz, 1H), 3.79 (ddd, J = 14.8, 11.4, 6.5 Hz, 1H), 3.34 – 3.17 (m, 1H), 2.78
(dd, J = 17.3, 6.2 Hz, 1H), 2.17 (d, J = 10.3 Hz, 1H), 2.04 (d, J = 11.2 Hz, 1H), 1.93 – 1.76 (m, 2H),
1.74 – 1.63 (m, 2H), 1.61 - 1.37 (m, 3H), 1.21 – 1.04 (m, 1H). 13C-NMR (75 MHz, CDCl3) δ[ppm]:
163.4, 147.1, 137.6, 134.4, 133.2, 129.5, 129.1, 127.9, 126.6, 125.9, 119.6, 119.2, 113.2, 68.9,
54.6, 45.0, 32.5, 30.9, 26.0, 25.6, 23.8. HRMS (ESI): m/z [M + H]+ calcd for C22H24N2O + H:
333.1961; found: 333.1969. HPLC (Chiralpak IC column, 75:25 hexanes/isopropanol, 1 ml/min);
tr = 15.5 (major), 17.4 (minor) min.
5-(2-Chlorophenyl)-4b,5,12,13-tetrahydro-6H-isoquinolino[2,1-a]quinazolin-6-one (3g)[13]
Following the General Catalytic Procedure, the reaction of N-aryl benzamide 2g (36.3 mg,
0.10 mmol, 1.0 eq.) provided, after column chromatography (CH2Cl2), the desired product (5.1 mg,
1
0.14 mmol, 14%, 50:50 e.r.) as a white solid. Rf = 0.26 (4:1) (SiO2, CH2Cl2). H-NMR (300 MHz,
CDCl3) δ[ppm]: 8.09 (dd, J = 8.0, 1.6 Hz, 1H), 7.49 – 7.42 (m, 1H), 7.42 – 7.36 (m, 1H), 7.11 – 7.02
(m, 5H), 6.99 – 6.89 (m, 2H), 6.87 – 6.70 (m, 2H), 6.17 (s, 1H), 3.94 – 3.83 (m, 1H), 3.47 (dt, J =
12.0, 5.9 Hz, 1H), 3.20 – 2.96 (m, 2H). 13C-NMR (75MHz, CDCl3) δ[ppm]: 164.8, 149.6, 141.3,
136.8, 134.9, 133.7, 130.8, 129.9, 129.6, 129.5, 129.2, 128.8, 128.5, 127.1, 125.9, 121.9, 118.1,
72.4, 45.4, 28.7. HRMS (ESI): m/z [M + H]+ calcd for C22H17ClN2O + H: 361.1102; found: 361.1110.
HPLC (Chiralpak IC column, 75:25 hexanes/isopropanol, 1 ml/min); tr = 30.1, 43.5 min.
4b,13-Dihydro-6H,12H-benzo[4,5][1,3]oxazino[2,3-a]isoquinolin-6-one (3h)[16a,c]
Following the General Catalytic Procedure, the reaction of the carboxylic acid 2h (25.3 mg,
0.100 mmol, 1 eq.) provided, after column chromatography (PE/EtOAc, 4:1), the desired product
(15.6 mg, 0.062 mmol, 62%) as a pale yellow solid. Rf = 0.55 (4:1) (SiO2, PE/EtOAc). 1H-NMR (300
MHz, CDCl3) δ[ppm]: 8.09 – 8.05 (m, 1H), 7.56 – 7.50 (m, 2H), 7.35 – 7.26 (m, 2H), 7.24 – 7.17 (m,
2H), 7.11 – 7.04 (m, 2H), 6.12 (s, 1H), 3.71 (dt, J = 12.0, 6.0 Hz, 1H), 3.50 – 3.38 (m, 2H), 3.07 (t, J
= 5.9 Hz, 2H). 13C-NMR (75 MHz, CDCl3) δ[ppm]: 165.2, 150.1, 135.3, 134.8, 131.1, 130.1, 129.5,

128.7, 128.5, 127.1, 122.2, 117.4, 117.1, 85.9, 43.8, 29.1. The analytical data are in accordance with
the literature.
6,6-Dimethyl-4b,13-dihydro-6H,12H-benzo[4,5][1,3]oxazino[2,3-a]isoquinoline (3i)
Following the General Catalytic Procedure, the reaction of the alcohol 2i (26.7 mg, 0.100 mmol,
1.0 eq.) provided, after column chromatography (PE/EtOAc, 32:1), the desired product (16.8 mg,
1
0.063 mmol, 63%, 54:46 e.r.) as a white solid. Rf = 0.32 (32:1) (SiO2, PE/EtOAc). H-NMR (300
MHz, CDCl3) δ[ppm]: 7.42 – 7.36 (m, 1H), 7.29 – 7.26 (m, 2H), 7.26 – 7.23 (m, 1H), 7.23 – 7.14 (m,
3H), 7.11 (dd, J = 8.1, 0.9 Hz, 1H), 7.04 – 6.96 (m, 1H), 5.50 (s, 1H), 3.59 (td, J = 11.2, 3.7 Hz, 1H),
3.41 (ddd, J = 11.5, 5.3, 3.6 Hz, 1H), 3.18 (ddd, J = 16.1, 11.2, 5.3 Hz, 1H), 2.94 (dt, J = 16.0, 3.6
Hz, 1H), 1.76 (s, 3H), 1.57 (s, 3H). 13C-NMR (75 MHz, CDCl3) δ[ppm]: 135.6, 135.4, 133.9, 128.8,
128.5, 128.1, 127.2, 126.5, 126.1, 122.1, 122.0, 116.6, 79.0, 76.0, 46.1, 31.9, 29.9, 29.2. HRMS
(ESI): m/z [M + H]+ calcd for C18H19NO + H: 265.1467; found: 265.1472. HPLC (Chiralpak OD-H
column, 90:10 hexanes/isopropanol, 1 ml/min); tr = 4.0 (major), 4.4 (minor) min.
6,7,11b,12-Tetrahydro-13H-isoquinolino[2,1-a]quinolin-13-one (3j)[16]
Following the General Catalytic Procedure, the reaction of the ketone 2j (25.0 mg, 0.10 mmol,
1.0 eq.) provided, after column chromatography (PE/EtOAc, 9:1), the desired product (13.0 mg,
1
0.052 mmol, 52%, 58:42 e.r.) as a yellow solid. Rf = 0.14 (9:1) (SiO2, PE/EtOAc). H-NMR (300
MHz, CDCl3) δ[ppm]: 8.01 (dd, J = 7.9, 1.6 Hz, 1H), 7.50 – 7.46 (m, 1H), 7.32 – 7.29 (m, 1H), 7.28 –
7.15 (m, 3H), 7.02 (d, J = 8.6 Hz, 1H), 6.84 (t, J = 7.4 Hz, 1H), 4.76 (dd, J = 13.7, 2.5 Hz, 1H), 4.19 –
4.05 (m, 1H), 3.29 – 3.05 (m, 3H), 2.99 – 2.90 (m, 1H), 2.84 – 2.75 (m, 1H). The analytical data are
in accordance with the literature. HPLC (Chiralpak OJ-H column, 85:15 hexanes/isopropanol,
1 ml/min); tr = 4.8 (major), 5.1 (minor) min.
Results and Discussion
Initially, a small family of Click-BINOL-derived chiral phosphoric acids 1 was synthetized (Scheme
2). Thus, starting from commercially available (S)-BINOL, we employed our early procedure for the
preparation of the 3,3’-diazido BINOL derivative 4,[15a] which implies a first MOM protection and an
ortho-directed lithiation/substitution sequence. Subsequent copper-catalyzed alkyne-azide
cycloaddition reaction (CuAAC) and MOM-deprotection led to the corresponding Click-BINOLs 6a
and 6b. Finally, phosphorylation with phosphoryl trichloride and acid work-up delivered the desired
phosphoric acids 1a and 1b, bearing a phenyl and a mesityl group at the triazole units, respectively.
Similarly, 6,6’-alkyl substituted BINOL-diazides 11-13 were easily prepared in gram scale. The direct
bromination of (S)-BINOL and reaction with MOM-chloride led to the corresponding dibromo-BINOL
7, which was subjected to a Kumada cross-coupling with octyl, dodecyl and octadecyl magnesium
bromide[13] and subsequent azide formation. CuAAC with various bulky aryl (Mes, mesityl; Trip,

2,4,6-triisopropylphenyl; BDIP, 4-bromo-2,6-diisopropylphenyl) and alkyl (Ad, 1-adamatyl)
substituted terminal alkynes followed by MOM-deprotection and phosphorylation, provided the
catalysts 1c-h in moderate to good overall yields. Finally, under non-optimized conditions, the more
acidic triflamide derivative 1c# was also prepared from the corresponding BINOL 6c.
In order to investigate the importance and effect of the triazole units on the catalytic activity of these
new Click-PA catalysts, we next decided to explore them in the intramolecular asymmetric C–H
functionalization of tetrahydroisoquinoline-N-benzamides, previously studied by Toste and
co-workers.[13] Therefore, the reaction with benzamide 2a in the presence of our catalysts was first
optimized (Table 1). It is important to note the strong background reaction with this type of THIQ-N-
benzamine substrates 2 (entry 1). Consequently, in order to achieve high enantioselectivities a
potent catalyst would be required. Therefore, the start point of our study was the screening of the
catalysts 1a-e under analogous reported conditions: Na3PO4 as base to form in situ the active
-
phosphate catalyst and a TEMPO oxoammonium salt (AcNHT+BF4 ) as oxidant in toluene (dilution
0.025 M) as apolar solvent to favor the formation of close ion-pairs at room temperature (entries 2-
6). Already with the simplest catalysts 1a and 1b, the effect of the substitution at the triazole rings
could be observed. Thus, an inversion on the enantioselectivity was detected when replacing a
phenyl for a bulkier mesityl group (entries 2 and 3). The introduction of a linear C8-alkylic chain in
the BINOL-backbone was beneficial, leading to 3a in an improved enantiomeric ratio (1c, 66:34 e.r.,
entry 4). Similar results were obtained with the catalysts 1d and 1e bearing bulkier Trip and Ad
groups, respectively (entries 5-6). The screening of solvents was next carried out with 1c. As
expected the solvent had an important effect on the enantioselectivity of the reaction. Whereas p-
xylene showed a slightly higher enantioinduction (70:30 e.r., entry 7), ethereal solvents such as
simple Et2O provided the best results (78:22 e.r., entry 9). The performance of the triflamide
derivative 1c# and the catalysts 1d-f was also tested in Et2O as solvent (entries 10-13).
Nevertheless, they were inferior to the mesityl-subtituted catalyst 1c. Considering the presumable
positive effect of the octyl chains by enhancing the catalyst’s solubility in the used apolar solvents,
other structures with longer alkyl rests such as dodecyl (1g) and octadecyl (1h) were then
investigated (entries 14 and 15). Conversely, the shorter n-octyl chain in 1c remained superior and
this PA was further employed as catalyst of choice. Next, various inorganic bases such as
phosphates and carbonates, and ionic hydride abstractors or oxidants such as TEMPO and trityl salt
derivatives were explored (entries 16-20). However, the initially employed mixture of salts
-
(AcNHT+BF4 and Na3PO4) gave the higher enantioselectivity. It was also observed that the decrease
in the temperature (-20 and -40 °C, entries 21 and 22) was not beneficial, leading to less efficient
asymmetric reactions. Lastly, the use of lower catalytic loadings (5 and 2.5 mol%, entries 23 and 24)

was also translated in a gradual decrease of the enantioinduction.
The substitution and nature of the nucleophile was then studied with our identified optimal reaction
-
conditions: 10 mol% of catalyst 1c, Na3PO4 as base, AcNHT+BF4 as oxidant in Et2O at room
temperature (Scheme 3). Differently benzyl-substituted benzamides 2 led to the corresponding
quinazolinones 3a-c in comparable moderate enantioselectivities (71:29 – 78:22 e.r.). Moreover, the
reaction with a chiral substrate 2d provided a similar level of diastereoselectivity (3d, 63:27 d.r.),
which turned out to be opposite to the one obtained in the uncatalyzed reaction (22:68 d.r.).
Unexpectedly, a change in the nature of the nucleophilic unit on the substrate from a N-benzyl
benzamide to an unsubstituted (NH2, 2e), N-alkyl (cyclohexyl, 2f) or N-aryl (2-chlorophenyl, 2g)
benzamide proceeded to the expected products 3e-g, although in inferior yields and low or
imperceptible enantioselectivities. Moreover, the formation of C-O or C-C bonds by reaction of the
carboxylic acid 2h and tertiary alcohol 2i or methyl ketone 2j also took place, leading to the
corresponding products in similar low enantiomeric inductions.
It is important to mention that the reaction could be scaled-up 5 times to a 1.0 mmol scale, leading to
only a slightly detriment to the enantioselectivity. Thus, the reaction with 2a (>340 mg) provided the
quinazolinone product 3a in a good 95% yield and 70:30 e.r. Furthermore, we observed that the
racemic compounds 3 possess a high crystallinity, allowing reaching extremely high
enantioselectivities (up to 99:1 e.r. for 3a) by the simple recrystallization (by removal of the racemic
crystals from the product of the catalytic reactions). Consequently, in order to avoid getting incorrect

e.r. values, acetonitrile was used to completely dissolve the probes for the HPLC analyses.[28]
Lastly, a comparison of the effectiveness of our developed chiral Click-BINOL-PA catalysts 1 with
commercially available derivatives and the previously reported regioisomeric triazole-BINOL-PA 1C’
in the model asymmetric C-H bond functionalization reaction of benzamide 2a was carried out
(Figure 2). The presence of the triazole groups is crucial to achieve enantiomeric induction. Thus,
standard chiral phosphoric acids such as TRIP® provided the racemic product, while the Click-
BINOL-PAs 1c and 1C’ showed certain levels of enantioselectivity. In this regard, our best Click-
BINOL-PA catalysts 1c afforded a moderate enantioselectivity (78:22 e.r.), while the catalyst 1C’,
which only differ in the rearrangement of the triazole units, led to an enhanced enantiomeric ratio
value (89:11 e.r.). The fact that the reaction with N-benzylic amides provided the best enantiomeric
results might be explained by the already proposed essential  interaction between the triazole
ring of the catalyst 1C’ and related structures and the benzylic substituent at the benzylamide.[13b]
However, the observation of a match / mismatch effect depending on the regioisomeric triazoles
employed suggest an additional positive interaction of the triazole units with the substrate and/or
ionic iminium intermediate, which might facilitate the effective formation of the required chiral close
ion-pair. Furthermore, the spatial disposition of the substituents on the triazoles in 1C’ permitted a
torsion angle of 90° in the transition state, which was proposed to be also key for attaining high
enantioinductions.[13b]
A simplified plausible mechanism is shown in Scheme 3, in which the key step to form a close ion-
pair B and allow chirality transfer is the counter-anion exchange between the active Click-phosphate
-
catalyst I and the iminium intermediate A (pathway A) and/or ionic oxidant (AcNHT+BF4 ) (pathway
B). Aiming at gaining more information on the counter-anion exchange, a reaction using
stoichiometric amounts of the phosphoric acid 1c was made (Scheme 4). For this purpose, the
Click-BINOL-PA 1c, the base and the oxidant were reacted for 20 min before adding the substrate
2a. Under these conditions, the same 78:22 enantiomeric ratio was obtained, showing that the anion
exchange was as effective in the catalytic as in the stoichiometric reaction.
Conclusions
To sum up, new chiral triazole-containing phosphoric acids have been developed and employed as
catalysts for the intramolecular enantioselective oxidative C–H bond functionalization of
tetrahydroisoquinolines. The presence of the triazole groups on the catalysts was key to achieve the
transfer of chirality to the products. Moderate enantioselectivities were obtained with the THIQ-N-

benzamide substrates, whereas the related regioisomeric catalysts seemed to be more effective for
this transformation. The formation of a chiral close ion-pair between the phosphate catalyst and the
iminium ion intermediate, which stays in equilibrium with the achiral species, is essential for
success. Therefore, the design of further superior catalyst structures is still needed to attain elevated
enantioselectivities in further asymmetric C–H bond functionalization reactions that relies on
counter-anion organocatalysis.
Supplementary data
Electronic supplementary information (ESI) is available: Procedures and characterization of starting
materials; NMR and HPLC collection of new compounds.
Acknowledgements
The Deutsche Forschungsgemeinschaft (DFG) is gratefully acknowledged for financial support. D.
G. thanks the Deutscher Akademischer Austauschdienst (DAAD) and the University of Regensburg
for an iPur PhD-exchangefellowship.
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study since the racemic compound was crystallized-out in the HPLC vials when dissolving the
probes in a 90:10 hexane/iPrOH mixture, thus enhancing the e.r. in solution.

Click-BINOL-Phosphates for C-H functionalization
(Toste)
this work:
N
N
N
N
N
N
R'
R''
R''
R'
O
O
O
O
O
vs.
P
P
X
O
O
O
X
R''
R'
R''
N
N
N
N
R'
N
N
N
N
N
first Click-BINOLs:
LA metal-catalysis
R'
OH
OH
+ Ti(iPrO)4 + Et2Zn
R'
N
N
N
Figure 1. Click-BINOL derivatives in asymmetric catalysis
Figure 2. Comparison of PA-catalysts in the model intramolecular C-H functionalization reaction