Azobisisobutyronitrile-Initiated Oxidative C-H Functionalization of Simple Alcohols with Diaryl(arylethynyl)phosphine Oxides: A Metal-Free Approach toward Hydroxymethyl Benzo[ b]phosphole Oxides and 6 H-Indeno[2,1- b]phosphindole 5-Oxide Derivatives

Article abstract of DOI:10.1021/acs.joc.0c00118

The first metal-free and facile radical addition/cyclization of simple alcohols with diaryl(arylethynyl)phosphine oxides has been described with azobisisobutyronitrile as a radical initiator, affording an efficient and one-pot procedure to access a new cl

Full text of DOI:10.1021/acs.joc.0c00118

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Article
AIBN-Initiated Oxidative C-H Functionalization of Simple
Alcohols with Diaryl(arylethynyl)phosphine Oxides: A Metal-
free Approach towards Hydroxymethyl Benzo[b]phosphole
Oxides and 6H-indeno[2,1-b]phosphindole 5-oxide Derivatives
Jiami Guo, Chenlu Mao, Bin Deng, Liyi Ye, Yingwu Yin, Yuxing Gao, and Song Tu
J. Org. Chem., Just Accepted Manuscript • DOI: 10.1021/acs.joc.0c00118 • Publication Date (Web): 17 Apr 2020
Downloaded from pubs.acs.org on April 17, 2020
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AIBN-Initiated Oxidative C-H Functionalization of Simple
Alcohols with Diaryl(arylethynyl)phosphine Oxides: A
Metal-free Approach towards Hydroxymethyl
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Benzo[b]phosphole Oxides and 6H-indeno[2,1-b]phosphindole
5-oxide Derivatives
Jiami Guo,† Chenlu Mao,† Bin Deng,† Liyi Ye,† Yingwu Yin,† Yuxing Gao‡* and Song Tu†*
†Department of Chemical and Biochemical Engineering, College of Chemistry and Chemical Engineering,
Xiamen University, Xiamen 361005, Fujian, China.
‡Department of Chemistry and Key Laboratory for Chemical Biology of Fujian Province, College of
Chemistry and Chemical Engineering, Xiamen University, Xiamen 361005, Fujian, China.
RECEIVED DATE (will be automatically inserted after manuscript is accepted).
Table of Contents Graphic:
Abstract: The first metal-free and facile radical addition/cyclization of simple alcohols with
diaryl(arylethynyl)phosphine oxides has been described with AIBN as radical initiator, affording an efficient and
one-pot procedure to access
a
new class of hydroxymethyl benzo[b]phosphole oxides and
6H-indeno[2,1-b]phosphindole 5-oxides of potential application in organic materials via sequential
C(sp3)−H/C(sp2)−H functionalization. The method employs easily accessible starting materials, and is endowed
with high regioselectivity and broad functional group tolerance.
INTRODUCTION
Phosphorus-containing heterocycles have gained increasing attention from the synthetic community in the past
several years due to their extensive applications in research fields of organic synthesis, medicinal chemistry and
material chemistry.1 Particularly, benzo[b]phospholes as an important class of π-conjugated organo-phosphorus
compounds, have attracted widespread interests because of their inherent unusual optical, electronical and physical
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properties and broad applications as advanced organic optoelectronic materials and bioimaging probes.2 Thus, the
development of efficient approaches to such promising frameworks is of great interest and continues to attract the
attention of synthetic chemists. Traditional strategies for the synthesis of these motifs mainly rely on
intramolecular cyclization of alkynylarenes having ortho-phosphorus substituents in the presence of a
stoichiometric strong base and/or an expensive transition metal catalyst,2a,c,3 yet, these synthetic methods suffer
from the tedious multistep preparation for precursors and low functional group toleration. To overcome these
drawbacks, until recently, approaches based on intermolecular cycloadditions of aryl secondary phosphine oxides
with internal alkynes have been reported,4 but large amounts of environmentally unfriendly transition metals are
required in most of the cases (Scheme 1a), which lead to metal ions residue in the product affected its performance,
thus restraining their applications. Multicomponent one-pot construction of benzo[b]-phospholes has also been
disclosed, but their use encounters severe limitations owing to complex multistep reactions and low yields.5
Additionally, extensive surveys2,6 have clearly demonstrated that photoelectric properties of benzo[b]phospholes
for the required applications highly depended on their fine structure, resulting in an urgent demand for a large
number of structurally diverse benzo[b]-phospholes. Thus, developing convenient, practical, especially metal-free
methods for making a new type of benzo[b]phospholes from readily accessible materials is still highly desired.
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Scheme 1. Synthetic Approaches to Benzo[b]phosphole Derivatives.
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In recent years, direct functionalization of unreactive C-H bonds for the C-C bond formation through the radical
process has emerged as one of the most fascinating and powerful tools to construct complex molecules due to its
extraordinary profits of high step- and atom-economy and environmental friendliness in industrial processes and
green chemistry.7 In particular, the construction of a new C–C bond by direct catalytic C(sp3)-H functionalization
of alcohols have received wide attention from organic chemists,8 since this strategy could use simple alcohols as
starting materials to retain an active hydroxyl functional group in the product, which might be further derivatized
easily. Very recently, as promising alternatives and beneficial complements to making benzo[b]phosphole oxides,
our group successfully developed TBAI (tetrabutylammonium iodide) and copper-catalyzed radical
addition/cyclizations of diaryl(arylethynyl)phosphine oxides with simple toluene derivatives and cycloalkanes for
the synthesis of benzo[b]phosphole oxides.9a,b Yet, the potential of this methodology has not been studied well:
some examples9 only focused on simple toluene derivatives and alkanes which have no active functional group,
making them difficult to carry out further transformations (Scheme 1b). Given the significance of constructing a
new type of benzo[b]phospholes to create advanced optoelectronic materials, we envisioned this approach could be
extended to the synthesis of various new hydroxymethyl benzo[b]phosphole oxides from stable and readily
available alcohols, which could use the active hydroxyl functional groups as potential sites to generate larger
conjugated benzo[b]phosphole oxides via intramolecular Friedel-Crafts alkylation. However, direct introduction of
a hydroxyl group in such a process has never been reported to date. As part of our ongoing endeavors to develop
environmentally friendly protocols to constructing phosphorus-containing heterocycles,4c,e,9a,b herein, we would
like to reveal our further important progress in this field, and first disclosed a facile AIBN-initiated radical
cyclization of various readily available alcohols with diaryl(arylethynyl)phosphine oxides to assemble a wide
range of structurally complex hydroxymethyl benzo[b]phosphole oxides and 6H-indeno[2,1-b]phosphindole
5-oxide derivatives of potent interest in material chemistry by one-pot process under metal-free and base-free
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conditions, which proceeded through the sequence of C(sp3)−H bond cleavage, oxyalkylation of triple bond,
intramolecular cyclization and Friedel-Crafts alkylation accompanied by the construction of three new C-C bonds.
To the best of our knowledge, there is still no example of employing radical addition/cyclization of alcohols with
diaryl(arylethynyl)phosphine oxides to access novel hydroxymethyl benzo[b]phosphole oxides and
6H-indeno[2,1-b]phosphindole 5-oxide derivatives.
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RESULTS AND DISCUSSION
Initially, our investigations focused on the direct C−H functionalization of 2-propanol (2a) with diphenyl-
(phenylethynyl)phosphine oxide (1a) to optimize the reaction conditions (Table 1). Unfortunately, no desired
product 3a was observed using DTBP (di-t-butyl peroxide) as the oxidant at 100 °C for 24 hours (entry 1). A
subsequent survey on the role of other oxidants including DCP (dicumyl peroxide), TBPB (t-butyl
peroxybenzoate), TBHP (t-butyl hydroperoxide) and H2O2 for the aforementioned transformation disclosed that
TBHP could afford the desired product 3a in 45% yield (entry 5), while other oxidants examined were poorly
effective (TBPB, entry 4) or entirely ineffective (DCP and H2O2; entries 2-3). To advance the process further, the
o
effect of temperature was evaluated, with the finding that enhancing the temperature to 120 C could improve the
product yield up to 55% (entry 6), but further enhancing the reaction temperature led to the yield reduction (entry
7). Encouraged by this promising result, some initiators were evaluated, and it was found that AIBN was the
optimal initiator for the process and could increase the product yield up to 74%, but the addition of TBAI or CuBr
completely suppressed this reaction (entries 8-10), probably since some side-reactions including the oxidation of
2-propanol to acetone and the decomposition of TBHP in the presence of TBAI or CuBr, caused the oxidant TBHP to be
consumed quickly. These results indicated that AIBN might be beneficial to the generation and stabilization of
α-hydroxyalkyl radicals which are different from benzyl radicals and cycloalkyl radicals.9a,b Additionally, a lower
loading of AIBN (15 mol %) gave a similar yield, yet, using 10 mol % of AIBN led to the yield reduction (entries
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11-12). To our delight, we found that extending the reaction time to 36 hours gave rise to a higher yield of 85%
(entry 13). Altering the loading of TBHP could not promote the yield (entries 16-17). Noting that because some
side-reactions such as the oxidation of 2-propanol to acetone by TBHP and slow decomposition of TBHP would
consume TBHP under the present reaction system, an excess amount of TBHP was required for high yield. No
desired product was obtained without TBHP, revealing that TBHP plays a key role in this process with high
efficiency (entry 18). Under argon, the reaction still provided a similar yield of 84%, showing that it is not
sensitive to air and moisture (entry 19).
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Table 1. Optimization of the Reaction Conditionsa
entry
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initiator
—
oxidant
DTBP (5)
DCP (5)
temp (°C ) yield (%)
100
100
100
100
100
120
130
120
120
120
120
120
120
120
120
120
120
120
120
0
2
—
0
3
—
H2O2 (5)
0
4
—
TBPB (5)
TBHP (5)
TBHP (5)
TBHP (5)
TBHP (5)
TBHP (5)
TBHP (5)
TBHP (5)
TBHP (5)
TBHP (5)
TBHP (5)
TBHP (5)
TBHP (4)
TBHP (6)
—
18
45
55
51
0
5
—
6
—
7
—
8
TBAI (20)
CuBr (20)
AIBN (20)
AIBN (10)
AIBN (15)
AIBN (15)
AIBN (15)
AIBN (100)
AIBN (15)
AIBN (15)
AIBN (15)
AIBN (15)
9
0
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12
13b
14c
15c
16
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18
19d
74
60
75
85
82
78
52
83
0
TBHP (5)
84
aReaction conditions: 1a (0.2 mmol), 2a (2 mL), initiator (mol %), oxidant (equiv) and TBHP (70% in water) at
120 °C for 24 h under air. bFor 36 h. cFor 48 h. dUnder Ar.
With the optimized conditions in hand (Table 1, entry 13), the oxidative addition/cyclization of various
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diaryl(arylethynyl)phosphine oxides 1 with 2a was first investigated to understand the generality of this
methodology. As shown in Table 2, this method was found to be quite general, and a wide range of
diaryl(arylethynyl)phosphine oxides 1 with electron-rich groups and either electron-deficient groups on the
phenylethynyl moiety were all compatible with the present conditions and generated the desired products in
moderate to high yields, without a distinct electronic effect on the reactivity being observed. Chloro- and
bromo-substituted substrates could afford the target products (3f and 3g) in 84% and 80% yields, respectively,
revealing that the potential of the new approach for synthesizing highly functionalized molecules by next coupling
of these halide products. Notably, 1 bearing strong electron-deficient groups such as trifluoromethyl and cyano
could also participate in the reaction and gave the relative products 3h and 3i in moderate to high yields.
Interestingly, heterocyclic substrate 1j containing a pyridine ring also led to the desired product 3j in a good yield.
It is noteworthy that 1k gave a mixture of regioisomeric products 3k due to a radical mechanism involving similar
radical aryl migration.4a,b In addition, ethyl phenyl(phenylethynyl)-phosphinate 1l could also react with 2a to
provide 3l in a moderate yield of 61%. Importantly, using this novel method, even an active hydroxyl substituent
could successfully survive under the present conditions to give the desired products, providing a general and
powerful tool for the preparation of valuable hydroxymethyl benzo[b]phosphole oxides, which could be further
transformed easily.
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Table 2. Reaction Scope of Diaryl(phenylethynyl)phosphine Oxides with 2aa
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aReaction conditions: 1 (0.2 mmol), 2a (2 mL), AIBN (15 mol %), TBHP (70% in water, 5 equiv) at 120 oC for 36
h under air.
The generality of this C-H functionalization reaction was further evaluated by using various alcohols with
diphenyl(phenylethynyl)phosphine oxide 1a, and the results were shown in Table 3. We first investigated the
effect of primary alcohols with different carbon chain length on the reaction. Apart from 2a, other alcohols such as
ethanol 2b and 3-pentanol 2c were all suitable substrates, and the corresponding compounds 3m and 3n were
obtained in good yields of 65% and 60%, respectively. The straight chain alcohols like n-butanol 2d and n-hexanol
2e were also used as the reaction partners, but produced the corresponding products 3o and 3p in relatively lower
yields. Moreover, cyclohexanol 2f could also react with 1a to generate the expected product 3q in 40% yield.
Interestingly, oxidative C-H functionalization of 2-methoxy-ethan-1-ol 2g having four methylene C-H bonds and
three methyl C-H bonds proceeded with single-site selectivity at the less hindered secondary site, and furnished the
target product in a good yield of 65%, without finding other C-H functionalization products according to the
analysis of in situ 31P NMR. 2h having an acetamide unit could also provide the corresponding product 3s
selectively in a moderate yield. In addition, benzyl alcohol as the substrate did not generate the desired product 3t
due to the oxidation of benzyl alcohol to benzaldehyde in the presence of TBHP and AIBN. Fortunately, the
product 3m was recrystallized from ethyl acetate/n-hexane as colorless crystals, and the molecular structure of 3m
was determined by a single-crystal X-ray analysis.10 The results revealed that the hydroxymethyl moiety was
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preferentially installed at the α-position of the P=O bond and the regioselectivity was controlled by innate
electronic nature of the substrates.
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Table 3. AIBN-Initiated Radical Addition/Cyclization of Alcohols with 1aa
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aReaction conditions: 1a (0.2 mmol), alcohol 2 (2 mL), AIBN (15 mol %), TBHP (70% in water, 5 equiv) at 120
oC for 36 h under air.
Much attention has been paid to obtain intriguing physical and photoelectric properties through extending
π-electron systems of benzo[b]phospholes,6 since their properties heavily rely on the parent π-conjugated
frameworks due to the weak aromaticity of the phosphole ring.3c Notably, the compound 3 has an active hydroxyl
functional group, which provides a potential site to construct larger π-conjugated benzo[b]phosphole systems via a
simple Friedel-Crafts alkylation. To validate the feasibility of our designed strategy, the intramolecular
Friedel-Crafts alkylation of readily available 3a was investigated as a model reaction. Upon evaluating the reaction
conditions by variations of the acid, the solvent and temperature, the preferred reaction parameters for the
intramolecular cyclization were identified as follows: the reaction of 3a (0.2 mmol) in the presence of TfOH (50
mol %) in HFIP (1,1,1,3,3,3-hexafluoro-2-propanol, 1 mL) at 90 oC for 24 h, the desired macroconjugated
6H-indeno[2,1-b]phosphindole 5-oxide 4a was produced in an excellent yield of 96% (see the Supporting
Information for details). Based on this positive result, we next explored for direct synthesis of the compound 4a
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from 1a with 2a by a simple one-pot approach. To our delight, the expected 6H-indeno[2,1-b]phosphindole
5-oxide product 4a could be obtained in 80% yield via a one-pot process. Next, the one-pot reaction of various
diaryl-(aryethynyl)phosphine oxides with alcohols for the synthesis of diverse 6H-indeno[2,1-b]phosphindole
5-oxides 4 was surveyed. As shown in Table 4, various diaryl- (aryethynyl)phosphine oxides having both
electron-donating groups and electron-withdrawing groups were compatible with the reaction conditions and
generated the corresponding products 4a-4j in moderate to high yields. In addition to 2-propanol, other secondary
alcohols 2c and 2f could undergo the transformation to give the demand products 4i and 4j. Furthermore, the
product 4f was successfully crystallized from dichloromethane/n-hexane and determined by single-crystal X-ray
diffraction.10 Notably, the sequential C-H functionalization and intramolecular Friedel-Crafts alkylation can be
operated in one–pot, firstly providing a general and convenient approach to synthesize a new class of
macroconjugated 6H-indeno[2,1-b]phosphindole 5-oxides containing important benzo[b]phosphole core from
simple staring materials.
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Table 4. One-pot Synthesis of 6H-indeno[2,1-b]phosphindole 5-oxidesa
o
aReaction conditions: 1 (0.2 mmol), 2 (2 mL), AIBN (15 mol %), TBHP (70 % in water, 5 equiv) at 120 C under
air; after 36 h, removed solvent under vacuum; then added TfOH (50 mol %) and HFIP (1 mL) and stirred for 24 h
at 90 oC under air.
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To show the synthetic application of the present method, several experiments were performed (Scheme 2).
Notably, a gram-scale experiment was conducted to afford 3a in good yield by using 1a (10 mmol, 3.02 g) with 2a
under the optimal conditions, disclosing the process can be scaled to a gram-scale with good efficiency (Scheme
2a). Moreover, the compound 3a having a reactive hydroxyl unit as an effective reaction site could be easily
introduced a terminal alkenyl group through simple intramolecular dehydration or alcoholysis of acryloyl chloride
(Scheme 2b). In addition, as expected, the diyne 1m could also undergo the reaction to furnish a
bis(benzophosphole-3-yl)benzene moiety, which might be used in organic electronics,2c,3a followed by the
Friedel-Crafts alkylation of 3u producing an interesting 6,13-dihydro-s-indaceno-[2,1-b:6,5-b']bis(phosphindole)
5,12-dioxide framework (Scheme 2c).
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Scheme 2. Application Studies.
To demonstrate the possible mechanism of this AIBN-initiated addition/cyclization, the kinetic isotope effect
was examined by the reaction of deuterated 2-propanol with 1a, and a significant KIE was obtained with the kH/kD
= 4.56 (Scheme 2a), revealing that the C−H cleavage on the 2-propanol might be one of the rate-limiting steps of
the approach.11 Moreover, using 2 equivalents of BHT or 4 equivalents of TEMPO as the radical scavenger could
suppress the reaction completely, showing this reaction might undergo a free radical mechanism (Scheme 2b).
Scheme 3. Experiments for the Mechanism Study.
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Based on the above observations and relevant reports,4a,b,12 a plausible mechanism was outlined in Scheme 4.
First, the tert-butoxyl radical and 2-hydroxy-2-methyl-propanenitrile (CpOH) confirmed by the GC-MS analysis
were produced from TBHP and AIBN under heating.12. Then, the hydrogen atom of 2-propanol 2a was abstracted
by tert-butoxyl radical to generate α-hydroxyalkyl radical A. Next, an alkenyl radical B was generated through the
addition of A to the α-position of the P=O bond in 1a. Given the formation of two regioisomeric products, B might
proceed two paths to provide the product 3a by the dehydrogenation of intermediate C or F.4a,b Subsequent
elimination of the OH group in 3a easily took place with the aid of a Bronsted acid, TfOH, to deliver the tertiary
carbocation intermediate G, which is finally transformed to the desired product 4a via intramolecular
Friedel-Crafts alkylation.
Scheme 4. Proposed mechanism.
Table 5. The optical properties of 3a-3u, 4a-4k, 5a and 6aa
compound
λabs (nm)
319
λemb (nm)
386
φF c (%)
0.67
1.1
τd (ns)
1.05
3a
3b
3c
343
394
1.23
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1.3
1.31
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0.96
2.1
1.6
1.1
2.3
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3.3
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2.9
2.9
1.2
3.7
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1.34
1.01
0.726
1.67
1.09
0.993
1.94
—
3d
3e
3f
3g
3h
3i
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3j
3k
3l
0.952
1.39
1.73
1.04
0.965
1.46
5.48
1.50
13.72
11.41
14.32
12.94
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9.78
10.89
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7.79
17.42
1.03
1.19
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aIn solutions of CH2Cl2 (5×10-5 M); bEmission maxima upon excitation at the absorption maximum wavelengths;
cAbsolute fluorescence quantum yields determined by a calibrate integrating system; dFluorescence lifetime.
The optical properties of 3a-3u, 4a-4k, 5a and 6a in dilute CH2Cl2 were investigated and were summarized in
Table 5. And the absorption and fluorescence spectra of 3a, 3u, 4a and 4k were shown in Figure 1. In the UV-vis
absorption spectra, 4a and 4k displayed red-shifted main absorption peak at 340 nm and 361 nm in comparison
with 319 nm of 3a and 330 nm of 3u. These redshifts might be attributed to extending π-conjugation and enforcing
planar rigidity of compound 4.13 Additionally, the larger conjugated 4a and 4k exhibited different fluorescence
maximum wavelengths from 3a and 3u in the range of 386-440 nm. The fluorescence quantum yields (φF) of 4a
and 4k are 52% and 65%, respectively, which are higher than those of 3a (0.67%) and 3u (8.9%). Moreover, the
more emissive 4a and 4k showed longer fluorescence lifetimes than the less emissive 3a and 3u. These interesting
results indicated that a novel type of 6H-indeno[2,1-b]phosphindole 5-oxide derivatives might find potential
application as advanced organic optoelectronic materials.
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3a 4a
Fig. 1. (a) UV-vis absorption spectra and (b) fluorescence spectra of solutions of 3a, 3u, 4a and 4k in CH2Cl2
(5×10-5 M). Photographs of 3a and 4a in CH2Cl2 (5×10-5 M) under irradiation with UV light at 365 nm were
shown in the inset.
CONCLUSION
In summary, we revealed the first AIBN-initiated oxidative radical addition/cyclization of various readily
available alcohols with diaryl(arylethynyl)phosphine oxides, providing a facile and environmentally benign
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synthetic route to structurally diverse hydroxyalkyl benzo[b]phospholes through sequential C(sp3)−H/C(sp2)−H
functionalization under metal-free and base-free conditions. Attractively, a rapid introduction of an active hydroxyl
into the product represents a prominent advantage of this method. Worthy of note is that the convenient synthesis
of novel extending conjugated 6H-indeno[2,1-b]phosphindole 5-oxide derivatives of excellent optical properties
was firstly realized from alcohols in one pot. Most importantly, the present method avoids the residual heavy metal
in the target product, eliminating the effect on its performance for organic electronic devices. Additionally, easily
accessible starting materials, good functional group compatibility, excellent regioselectivity and high atom- and
step-economy will open a new avenue for the preparation of a new family of important benzo[b]phosphole oxide
frameworks and should find broad applications in synthetic and material science.
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EXPERIMENTAL SECTION
1
The H, 13C and 31P NMR spectra were recorded at 298 K in deuterated solvents (CDCl3) using Bruker Avance
400 MHz or 500 MHz spectrometer. NMR chemical shifts were determined relative to CDCl3 as the internal
reference (δH = 7.26 ppm, δC = 77.16 ppm). NMR data are represented as follows: chemical shift, multiplicity (s =
singlet, d = doublet, t = triplet, q = quartet, m = multiplet), coupling constants in Hertz (Hz), integration. HRMS
spectra of all compounds were recorded on a Waters Micromass LCT Premier TOF-MS apparatus. Infrared spectra
were recorded on a Nicollet Avatar 330 spectrometer. Melting points were recorded on a MP120 Digital
Melting-Point apparatus. The optical properties were recorded on F7000 and FLS980 fluorescence spectrometers
and UV-2550 ultraviolet-visible spectrophotometer. The products were purified by column chromatography on
silica gel 300-400 mesh. Flash column chromatography purification was carried out by a gradient elution method
using ethyl acetate (EA) in light petroleum ether (PE).
All reactions were performed in oven-dried Schlenk tubes. 1a-1m substrates were prepared according to the
known reference.14 Anhydrous solvents (THF, CH2Cl2) were purchased and used without further purification, and
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toluene and Et3N were distilled from sodium and CaH2, respectively, prior to use. Other reagents were purchased
from commercial sources and used without further purification.
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A typical procedure for the synthesis of 1a. A toluene solution (5.0 mL) of ethynylbenzene ((219.6 μL, 2.0
mmol), CuI (38.0 mg, 0.2 mmol), Ph2PCl (441.2 μL, 2.4 mmol), and Et3N (454.4 μL, 4.0 mmol) was stirred under
nitrogen at 80 °C for 8 h. After usual workup with CH2Cl2 and NH4Claq, the combined organic layer was washed
with brine, and dried over MgSO4. After filtration, the solvents were evaporated. The crude product was used for
next step without purification. To a THF solution (20.0 mL) of the crude diphenyl(phenylethynyl)phosphine was
added H2O2aq (30%, 1.0 mL, 8.0 mmol) slowly at 0 °C, and the mixture was stirred at rt for 2 h. After workup with
CH2Cl2 and water, the combined organic layer was washed with brine and dried over MgSO4. After filtration, the
solvents were evaporated. The crude product was subjected to column chromatography on silica gel
(hexane/AcOEt, 3:1) to afford 1a in a pure form (525.9 mg, 87% yield). Other compounds (1b-1m) are also
synthesized based on the above procedure.
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Procedure for the gram-scale synthesis of 3a. In an oven dried Schlenk tube equipped with a magnetic stir
bar, 1a (0.2 mmol, 3.02 g), AIBN (1.5 mmol, 246.3 mg) and TBHP (70% in water, 50 mmol, 6.4 g) were mixed in
o
2a (60 mL) and then stirred at 120 C (in oli bath) for 36 h under air. The mixture was cooled down to room
temperature and purified by flash chromatography (petroleum ether/ethyl acetate = 3:1-1:1) to afford the
corresponding product 3a (2.52 g, 70% yield).
General procedure for the synthesis of hydroxymethyl benzo[b]phosphole oxides 3a-3s. In an oven-dried
Schlenk tube equipped with a magnetic stir bar, diaryl(arylethynyl) phosphine oxide 1 (0.2 mmol), AIBN (4.9 mg,
0.03 mmol, 15 mol %) and TBHP (70% tert-butyl hydroperoxide in water, 128.7 mg, 1.0 mmol, 5 equiv) were
mixed in 2 (2 mL) and then stirred at 120 oC (in oil bath) for 36 h under air. The mixture was cooled down to room
temperature and purified by flash chromatography (petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to afford the
corresponding products.
2-(2-Hydroxypropan-2-yl)-1,3-diphenylphosphindole 1-oxide (3a).4b Purified by flash chromatography (silica gel,
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petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid, mp 214.3-216.1 °C, 61.2 mg
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1
(85%); H NMR (CDCl3, 400 MHz): δ 1.11 (s, 3H), 1.31 (s, 3H), 3.14 (s, 1H), 6.72 (dd, J = 2.3, 7.6 Hz, 1H),
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7.24-7.30 (m, 3H), 7.34 (t, J = 7.5Hz, 1H), 7.40-7.52 (m, 6H), 7.58 (t, J = 8.1 Hz, 1H), 7.78 (dd, J = 7.0, 12.8 Hz,
2H); 13C{1H} NMR (CDCl3, 400 MHz) δ 30.8 (d, J = 1.4 Hz), 31.8 (d, J = 1.7 Hz), 73.5, (d, J = 7.2 Hz), 123.6 (d,
J = 11.2 Hz), 128.4 (d, J = 5.5 Hz), 128.5 (d, J = 10.7 Hz), 128.6 (d, J = 3.0 Hz), 128.7 (d, J = 1.4 Hz), 128.8 (d, J
= 8.9 Hz), 128.9 (d, J = 11.0 Hz), 130.7 (d, J = 100.5 Hz), 131.0 (d, J = 11.0 Hz), 131.3 (d, J = 101.1 Hz), 131.9 (d,
J = 2.2 Hz), 132.8, 134.8 (d, J = 17.0 Hz), 144.5 (d, J = 94.7 Hz), 145.1 (d, J = 28.1 Hz), 148.7 (d, J = 20.6 Hz);
31P{1H} NMR (CDCl3, 400 MHz): δ 42.3; HRMS m/z (M+Na+) calcd for C23H21O2PNa+: 383.1181, found
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383.1184; IR (film) νmax: 3308, 1448, 1191, 1137, 712, 514 cm-1
.
2-(2-Hydroxypropan-2-yl)-1-phenyl-3-(p-tolyl)phosphindole 1-oxide (3b). Purified by flash chromatography
(silica gel, petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid, mp 220.3-221.1 °C,
47.9 mg (64%); 1H NMR (CDCl3, 500 MHz): δ 1.13 (s, 3H), 1.32 (s, 3H), 2.43 (s, 3H), 3.08 (s, 1H), 6.72 (dd, J =
2.7, 7.5 Hz, 1H), 7.12-7.30 (m, 2H), 7.27-7.36 (m, 4H), 7.42-7.45 (m, 2H), 7.50-7.57 (m, 2H), 7.78-7.80 (m, 2H);
13C{1H} NMR (CDCl3, 400 MHz) δ 30.9, 31.8, 36.8, 73.5, (d, J = 7.1 Hz), 123.7 (d, J = 11.9 Hz), 128.3, 128.5 (d,
J = 9.7 Hz), 128.6, 128.8 (d, J = 12.6 Hz), 129.0 (d, J = 10.4 Hz), 129.5 (d, J = 27.9 Hz), 130.6 (d, J = 101.7 Hz),
131.1 (d, J = 11.1 Hz), 131.2 (d, J = 103.4 Hz), 131.6, 132.0 (d, J = 2.7 Hz), 132.9, 138.3, 144.6 (d, J = 92.3 Hz),
145.4 (d, J = 30.0 Hz), 149.2 (d, J = 20.5 Hz); 31P{1H} NMR (CDCl3, 500 MHz): δ 41.8; HRMS m/z (M+H+)
calcd for C24H23O2PH+: 375.1508, found 375.1511; IR (film) νmax: 3308, 2875, 1448, 1191, 1137, 712, 514 cm-1
.
3-(4-(Tert-butyl)phenyl)-2-(2-hydroxypropan-2-yl)-1-phenylphosphindole 1-oxide (3c). Purified by flash
chromatography (silica gel, petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid,
mp 221.3-222.1 °C, 55.8 mg (67%); 1H NMR (CDCl3, 500 MHz): δ 1.13 (s, 3H), 1.31 (s, 3H), 1.37 (s, 9H), 3.03 (s,
1H), 6.68 (dd, J = 2.5, 7.2 Hz, 1H), 7.17 (dd, J = 1.8, 8.0 Hz, 1H), 7.20 (dd, J = 1.8, 8.0 Hz, 1H), 7.28 (dd, J = 3.2,
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7.1 Hz, 1H), 7.34 (t, J = 7.6 Hz, 1H), 7.41-7.56 (m, 6H), 7.78 (dd, J = 7.1, 12.8 Hz, 2H); 13C{1H} NMR (CDCl3,
500 MHz) δ 30.9 (d, J = 1.6 Hz), 31.35, 31.8 (d, J = 1.8 Hz), 34.7, 73.5, (d, J = 7.3 Hz), 123.7 (d, J = 11.4 Hz),
125.6 (d, J = 40.3 Hz), 128.1 (d, J = 39.9 Hz), 128.4 (d, J = 9.4 Hz), 128.7 (d, J = 12.5 Hz), 128.9 (d, J = 10.8 Hz),
130.7 (d, J = 100.7 Hz), 131.0 (d, J = 11.0 Hz), 131.3 (d, J = 105.0 Hz), 131.6 (d, J = 16.2 Hz),131.9 (d, J = 2.3
Hz), 132.8 (d, J = 1.4 Hz), 144.3 (d, J = 91.8 Hz), 145.3 (d, J = 28.3 Hz), 149.0 (d, J = 20.5 Hz), 151.5; 31P{1H}
NMR (CDCl3, 500 MHz): δ 41.8; HRMS m/z (2M+Na+) calcd for C54H58O4P2Na+: 855.3703, found 855.3702; IR
(film) νmax: 3311 2928, 2695, 1513, 1178, 1129, 701, 514 cm-1.
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2-(2-Hydroxypropan-2-yl)-3-(4-methoxyphenyl)-1-phenylphosphindole 1-oxide (3d). Purified by flash
chromatography (silica gel, petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid,
mp 226.3-226.9 °C, 54.6 mg (70%); 1H NMR (CDCl3, 500 MHz): δ 1.13 (s, 3H), 1.31 (s, 3H), 2.93 (s, 1H), 3.87(s,
3H), 6.73 (dd, J = 2.4, 7.5 Hz, 1H), 7.00 (dd, J = 2.6, 8.4 Hz, 1H), 7.03 (dd, J = 2.6, 8.4 Hz, 1H), 7.16 (dd, J = 2.0,
8.2 Hz, 1H), 7.20 (dd, J = 2.3, 8.5 Hz, 1H), 7.29 (dd, 2.8, 7.1 Hz, 1H), 7.35 (t, J = 7.6 Hz, 1H), 7.41-7.44 (m, 2H),
748-7.56 (m, 2H), 7.77 (dd, J = 7.2, 12.9 Hz, 2H); 13C{1H} NMR (CDCl3, 500 MHz) δ 30.9 (d, J = 1.8 Hz), 31.8
(d, J = 2.7 Hz), 55.3, 73.5, (d, J = 7.2 Hz), 114.2 (d, J = 5.7 Hz), 123.6 (d, J = 11.5 Hz), 126.6 (d, J = 16.5 Hz),
128.4 (d, J = 9.6 Hz), 128.7 (d, J = 12.5 Hz), 128.9 (d, J = 10.6 Hz), 129.7 (d, J = 41.2 Hz), 130.7 (d, J = 100.7
Hz), 131.0 (d, J = 11.0 Hz), 131.3 (d, J = 105.0 Hz), 131.9 (d, J = 3.0 Hz), 132.9, 144.6 (d, J = 91.8 Hz）, 145.4 (d,
J = 28.9 Hz), 148.8 (d, J = 20.7 Hz), 159.6; 31P{1H} NMR (CDCl3, 500 MHz): δ 41.7; HRMS m/z (M+Na+) calcd
for C24H23O3PNa+: 413.0717, found 413.0713; IR (film) νmax: 2929, 1421, 1201, 1156, 718, 514 cm-1
.
3-(4-Fluorophenyl)-2-(2-hydroxypropan-2-yl)-1-phenylphosphindole 1-oxide (3e). Purified by flash
chromatography (silica gel, petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid,
1
mp 227.6-228.6 °C, 57.5 mg (76%); H NMR (CDCl3, 500 MHz): δ 1.13 (s, 3H), 1.32 (s, 3H), 3.51 (s, 1H), 6.70
(dd, J = 2.4, 7.9 Hz, 1H), 7.17-7.32 (m, 5H), 7.37 (t, J = 7.5 Hz, 1H), 7.42 (dd, J = 5.1, 8.0 Hz, 2H), 7.50 (t, J = 7.0
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Hz, 1H), 7.56 (t, J = 8.1 Hz, 1H) 7.77 (dd, J = 7.6, 12.7 Hz, 2H); 13C{1H} NMR (CDCl3, 500 MHz) δ 30.9 (d, J =
1.7 Hz), 31.8 (d, J = 1.8 Hz), 73.2, (d, J = 7.0 Hz), 115.9 (dd, J = 3.8, 21.6 Hz), 116.0 (d, J = 21.6 Hz), 123.4 (d, J
= 11.5 Hz), 128.6 (d, J = 9.8 Hz), 128.7 (d, J = 12.9 Hz), 129.0 (d, J = 10.0 Hz), 130.2 (d, J = 7.8 Hz), 130.5 (d, J
= 70.3 Hz), 130.6 (d, J = 11.0 Hz), 131.3 (d, J = 105.2 Hz), 132.0 (d, J = 2.5 Hz), 132.9, 145.0 (d, J = 6.7 Hz),
145.3 (d, J = 112.7 Hz), 147.7 (d, J = 21.0 Hz）, 162.6 (d, J = 248.4 Hz); 31P{1H} NMR (CDCl3, 500 MHz): δ 41.4;
HRMS m/z (M+Na+) calcd for C23H20FO2PNa+: 401.1077, found 401.1076; IR (film) νmax: 3298, 1502, 1224, 1174,
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725 cm-1
.
3-(4-Chlorophenyl)-2-(2-hydroxypropan-2-yl)-1-phenylphosphindole 1-oxide (3f). Purified by flash
chromatography (silica gel, petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid,
1
mp 224.0-225.2 °C, 66.2 mg (84%); H NMR (CDCl3, 400 MHz): δ 1.05 (s, 3H), 1.29 (s, 3H), 3.32 (s, 1H), 6.67
(dd, J = 1.9, 7.4 Hz, 1H), 7.20 (t, J = 8.3 Hz, 1H), 7.29 (dd, J = 4.0, 7.4 Hz, 2H), 7.35 (t, J = 7.5 Hz, 1H), 7.39-7.56
(m, 6H), 7.74 (dd, J = 8.0, 12.8 Hz, 2H); 13C{1H} NMR (CDCl3, 500 MHz) δ 30.9 (d, J = 1.8 Hz),31.8 (d, J = 1.6
Hz), 73.2, (d, J = 7.1 Hz), 116.0 (d, J = 21.6 Hz), 123.4 (d, J = 11.1 Hz), 128.8 (d, J = 16.6 Hz), 128.9 (d, J = 63.5
Hz), 129.0 (d, J = 34.2 Hz), 130.0 (d, J = 40.8 Hz), 130.4 (d, J = 100.8 Hz), 131.0 (d, J = 11.0 Hz), 131.7, 132.0 (d,
J = 2.6 Hz), 133.0, 133.2(d, J = 16.45 Hz), 134.5, 144.7 (d, J = 28.0 Hz), 145.3 (d, J = 91.4 Hz), 147.5 (d, J = 21.8
Hz); 31P{1H} NMR (CDCl3, 400 MHz): δ 41.5; HRMS m/z (M+H+) calcd for C23H20ClO2PH+: 395.0962, found
395.0962; IR (film) νmax: 3330, 1485, 1199, 1134, 721 cm-1.
3-(4-Bromophenyl)-2-(2-hydroxypropan-2-yl)-1-phenylphosphindole 1-oxide (3g). Purified by flash
chromatography (silica gel, petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid,
1
mp 225.2-226.1 °C, 70.1 mg (80%); H NMR (CDCl3, 500 MHz): δ 1.11 (s, 3H), 1.30 (s, 3H), 3.22 (s, 1H), 6.67
(dd, J = 2.4, 7.5 Hz, 1H), 7.13-7.17(m, 2H), 7.27-7.31(m, 1H), 7.35(t, J = 7.6 Hz, 1H), 7.40-7.43(m, 2H), 7.50(td,
J = 7.4, 1.2, 1H),7.56 (t, J = 8.2 Hz, 1H),7.60-7.64(m, 2H), 7.74 (dd, J = 7.1, 12.9 Hz, 2H); 13C{1H} NMR (CDCl3,
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500 MHz) δ 30.9 (d, J = 1.8 Hz), 31.9 (d, J = 1.8 Hz), 73.3, (d, J = 7.2 Hz), 122.6, 118.2, 123.2 (d, J = 11.2 Hz),
128.6 (d, J = 8.8 Hz), 128.7 (d, J = 12.2 Hz), 129.1 (d, J = 10.5 Hz),130.3 (d, J = 38.8 Hz), 130.4 (d, J = 102.3 Hz),
131.0 (d, J = 11.5 Hz), 131.8 (d, J = 21.9 Hz), 131.9 (d, J = 34.2 Hz), 132.0 (d, J = 2.7 Hz), 132.5 (d, J = 107.7
Hz), 133.8 (d, J = 16.3 Hz), 144.7(d, J = 28.3 Hz), 145.3 (d, J = 90.8 Hz), 147.4 (d, J = 21.5 Hz); 31P{1H} NMR
(CDCl3, 500 MHz): δ 41.5; HRMS m/z (M+Na+) calcd for C23H20BrO2PNa+: 461.0277, found 461.0276; IR (film)
νmax: 3330, 1485, 1198, 1134, 744 cm-1.
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2-(2-Hydroxypropan-2-yl)-1-phenyl-3-(4-(trifluoromethyl)phenyl)phosphindole 1-oxide (3h). Purified by flash
chromatography (silica gel, petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid,
1
mp 221.0-221.8 °C, 71.1 mg (83%); H NMR (CDCl3, 500 MHz): δ 1.11 (s, 3H), 1.28 (s, 3H), 3.35 (s, 1H), 6.62
(dd, J = 2.5, 7.5 Hz, 1H), 7.29-7.32 (m, 1H), 7.36(t, J = 7.6 Hz, 1H), 7.39-7.44 (m, 4H), 7.50 (td, J = 7.3, 1.3,
1H),7.56 (t, J = 8.2 Hz, 1H), 7.73-7.78 (m, 4H); 13C{1H} NMR (CDCl3, 500 MHz) δ 30.9 (d, J = 1.5 Hz), 31.9 (d,
J = 1.5 Hz), 73.1, (d, JC-F = 7.2 Hz), 123.3 (d, J = 11.0 Hz), 123.9 (d, JP-F = 272.4 Hz), 125.5 (q, J = 3.4 Hz), 125.8
(q, J = 3.6 Hz), 128.7 (d, J = 12.6 Hz),128.9 (d, J = 19.5 Hz), 129.3 (d, J = 12.1 Hz), 130.3 (d, J = 101.6 Hz),
130.7 (d, J = 32.9 Hz), 131.0 (d, J = 11.1 Hz), 131.7, 132.1 (d, J = 2.7 Hz), 133.0, 139.0 (d, J = 16.5 Hz), 144.4 (d,
J = 27.9 Hz), 145.6(d, J = 90.9 Hz), 147.1 (d, J = 21.1 Hz); 31P{1H} NMR (CDCl3, 500 MHz): δ 41.5; HRMS m/z
(M+Na+) calcd for C24H20F3O2PNa+: 451.1045, found 451.1053; IR (film) νmax: 3288, 1428, 1268, 1171, 1125, 832,
701, 514 cm-1.
4-(2-(2-Hydroxypropan-2-yl)-1-oxido-1-phenylphosphindol-3-yl)benzonitrile
(3i).
Purified
by
flash
chromatography (silica gel, petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid,
1
mp 221.7-223.5 °C, 48.5 mg (63%); H NMR (CDCl3, 500 MHz): δ 1.13 (s, 3H), 1.26 (s, 3H), 3.27 (s, 1H), 6.59
(dd, J = 2.2, 7.1 Hz, 1H), 7.30-7.46(m, 6H), 7.52(dd, J = 1.6, 7.5 Hz, 1H), 7.57 (t, J = 8.2 Hz, 1H), 7.72-7.81 (m,
4H); 13C{1H} NMR (CDCl3, 500 MHz) δ 31.0 (d, J = 1.5 Hz), 31.8 (d, J = 1.9 Hz), 73.1, (d, J = 7.5 Hz), 112.5,
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118.2, 123.2 (d, J = 11.0 Hz), 128.8 (d, J = 12.6 Hz), 128.9 (d, J = 9.6 Hz), 129.4 (d, J = 10.3 Hz), 128.6 (d, J =
33.8 Hz), 130.0 (d, J = 101.7 Hz), 131.0 (d, J = 11.1 Hz), 131.2 (d, J = 105.6 Hz), 132.2 (d, J = 2.7 Hz), 132.4 (d, J
= 22.5 Hz), 133.1, 140.3 (d, J = 16.6 Hz), 144.1 (d, J = 28.0 Hz), 145.9 (d, J = 90.2 Hz), 146.6 (d, J = 21.2 Hz);
31P{1H} NMR (CDCl3, 400 MHz): δ 41.4; HRMS m/z (2M+Na+) calcd for C48H40N2O4P2Na+:793.2356, found
793.2356; IR (film) νmax: 3313, 2230, 1451, 1211, 11224, 706, 514 cm-1.
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2-(2-Hydroxypropan-2-yl)-1-phenyl-3-(pyridin-2-yl)phosphindole
1-oxide
(3j).
Purified
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chromatography (silica gel, petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid,
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mp 239.2-240.9 °C, 42.6 mg (59%); H NMR (CDCl3, 500 MHz): δ 1.21 (s, 3H), 1.32 (s, 3H), 4.68 (s, 1H),
6.93-6.94 (m, 1H), 7.31-7.35 (m, 1H), 7.39-7.46 (m, 4H), 7.49-7.52 (m, 2H), 7.59 (t, J = 8.3 Hz, 1H), 7.83-7.93 (m,
3H), 8.77 (s, 1H); 13C{1H} NMR (CDCl3, 400 MHz) δ 30.4, 31.5, 72.0, (d, J = 9.2 Hz), 123.4, 123.8 (d, J = 6.1
Hz), 124.8, 128.9 (d, J = 7.1 Hz), 129.0 (d, J = 3.6 Hz), 129.3 (d, J = 10.0 Hz), 129.9, 131.1 (d, J = 11.0 Hz), 132.6
(d, J = 94.5 Hz), 137.1 (d, J = 5.8 Hz), 149.8 (d, J = 6.0 Hz); 31P{1H} NMR (CDCl3, 500 MHz): δ 40.5; HRMS
m/z (2M+Na+) calcd for C44H40N2O4P2Na+:745.2356, found 745.2360; IR (film) νmax: 3262, 3188, 2982, 1456,
1191, 1137, 724, 514 cm-1.
Compounds 3k. Purified by flash chromatography (silica gel, petroleum ether/ethyl acetate from 3:1 to 1:1, v/v)
1
to give the desired products: Solid, 55.9 mg (72%); H NMR (CDCl3, 500 MHz): δ 1.11 (d, J = 5.4 Hz, 6H), 1.29
(d, J = 5.4 Hz, 6H), 2.26 (d, J = 22.0 Hz, 6H), 2.38 (d, J = 3.9Hz, 6H), 3.04 (s, 2H), 6.46-6.57 (m, 2H), 7.08-7.13
(m, 2H), 7.22-7.28 (m, 8H), 7.36 (d, J = 9.7 Hz, 1H), 7.41-7.50 (m, 7H), 7.64-7.70 (m, 4H); 13C{1H} NMR (CDCl3,
400 MHz) δ 21.3, 21.8, 21.9, 31.0 (d, J = 6.5 Hz), 31.9, 73.5 (t, J = 7.3 Hz), 123.5 (d, J = 11.8 Hz), 124.5 (d, J =
11.7 Hz), 127.3 (d, J = 102.7 Hz), 128.4 (d, J = 3.7 Hz), 128.5, 128.6, 128.7, 128.9 (t, J = 3.9 Hz), 129.3 (d, J = 9.7
Hz), 129.6 (d, J = 12.5 Hz), 129.6 (d, J = 13.0 Hz), 131.2 (d, J = 11.4 Hz), 131.2 (d, J = 10.9 Hz), 132.0, 133.4 (d,
J = 1.8 Hz), 135.0, 135.1, 135.2, 139.3 (d, J = 10.2 Hz), 142.5, 142.6, 143.2, 143.7, 143.9, 144.6, 145.5, 145.7,
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148.6 (d, J = 20.1 Hz), 148.8 (d, J = 20.7 Hz); 31P{1H} NMR (CDCl3, 500 MHz): δ 42.1, 42.3.
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1-Ethoxy-2-(2-hydroxypropan-2-yl)-3-phenylphosphindole 1-oxide (3l). Purified by flash chromatography (silica
gel, petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid, mp 182.2-183.6 °C, 40.0
mg (61%); 1H NMR (CDCl3, 500 MHz): δ 1.33 (s, 3H), 1.38 (t, J = 7.0 Hz, 6H), 3.02 (s, 1H), 4.21-4.36 (m, 2H),
6.56-6.59 (m, 1H), 7.17-7.21 (m, 2H), 7.26-7.32 (m, 2H), 7.41-7.46 (m, 3H), 7.60-7.64 (m, 1H); 13C{1H} NMR
(CDCl3, 500 MHz) δ 16.6 (d, J = 6.5 Hz), 30.6 (d, J = 2.7 Hz), 31.5 (d, J = 2.7 Hz), 62.4 (d, J = 6.5 Hz), 72.7, (d, J
= 6.5 Hz), 123.5 (d, J = 13.8 Hz), 127.0 (d, J = 116.2 Hz), 127.0 (d, J = 8.9 Hz), 128.3, 128.4 (d, J = 5.3 Hz), 128.6
(d, J = 12.7 Hz), 128.7 (d, J = 4.6 Hz), 128.8, 132.9 (d, J = 1.8 Hz), 134.5 (d, J = 19.8 Hz), 140.0 (d, J = 118.7 Hz),
142.8 (d, J = 36.5 Hz), 147.4 (d, J = 26.4 Hz); 31P{1H} NMR (CDCl3, 500 MHz): δ 47.8; HRMS m/z (M+Na+)
calcd for C19H21O3PNa+:351.1121, found 351.1121; IR (film) νmax: 3277, 1590, 1489, 1352, 1137, 712, 514 cm-1.
2-(1-Hydroxyethyl)-1,3-diphenylphosphindole 1-oxide (3m). Purified by flash chromatography (silica gel,
petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid, mp 221.2-222.0 °C, 45.0 mg
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(65%); H NMR (CDCl3, 400 MHz): δ 1.47 (d, J = 6.6 Hz, 3H), 2.29 (s, 1H), 4.70-4.76 (m, 1H), 7.22 (d, J = 6.7
Hz, 1H), 7.28-7.34 (m, 3H), 7.37-7.42 (m,3H), 7.44-7.51 (m, 4H), 7.57 (t, J = 8.6 Hz, 1H),7.78 (dd, J = 6.9, 12.8
Hz, 2H); 13C{1H} NMR (CDCl3, 400 MHz) δ 23.7 (d, J = 1.9 Hz), 66.2 (d, J = 7.6 Hz), 123.7 (d, J = 10.7 Hz),
128.4 (d, J = 41.5 Hz), 128.7 (d, J = 4.4 Hz), 128.8 (d, J = 11.0 Hz), 129.2 (d, J = 11.1 Hz), 130.9 ( d, J = 100.5
Hz), 131.0 (d, J = 11.0 Hz), 131.9 (d, J = 2.6 Hz), 132.4 (d, J = 106.8 Hz), 132.8, 133.5 (d, J = 15.2 Hz), 139.8 (d,
J = 93.2 Hz), 143.7 (d, J = 27.1 Hz), 150.2 (d, J = 20.5 Hz); 31P{1H} NMR (CDCl3, 400 MHz): δ 39.8; HRMS m/z
(M+H+) calcd for C22H19O2PH+: 347.1195, found 347.1195; IR (film) νmax: 3297, 1439, 1183, 1100, 716 cm-1.
2-(3-Hydroxypentan-3-yl)-1,3-diphenylphosphindole 1-oxide (3n). Purified by flash chromatography (silica gel,
petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid, mp 231.1-232.8 °C, 46.6 mg
(60%); 1H NMR (CDCl3, 400 MHz): δ 0.41 (t, J = 7.4 Hz, 3H), 0.95 (t, J = 7.4 Hz, 3H), 1.24-1.39 (m,
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2H),1.43-1.55 (m, 2H), 3.39 (s, 1H), 6.66 (dd, J = 2.4, 7.3 Hz, 1H), 7.17-7.20 (m, 1H), 7.22 (d, J = 6.7 Hz, 1H),
7.28-7.33 (m, 1H), 7.36-7.49 (m, 7H), 7.58 (t, J = 8.4 Hz, 1H),7.67-7.72 (m, 2H); 13C{1H} NMR (CDCl3, 400
MHz) δ 7.76, 7.93, 33.5 (d, J = 2.1 Hz), 35.1 (d, J = 1.6 Hz), 79.6 (d, J = 5.2 Hz), 123.4 (d, J = 11.0 Hz), 127.6,
128.1 (d, J = 21.2 Hz), 128.4 (d, J = 4.7 Hz), 128.5, 128.7, 128.8 (d, J = 3.7 Hz), 130.5 ( d, J = 101.7 Hz), 131.1 (d,
J = 103.7 Hz), 131.8 (d, J = 10.9 Hz), 131.9 (d, J = 2.4 Hz), 133.0, 134.7 (d, J = 16.5 Hz), 143.4 (d, J = 91.5 Hz),
145.7 (d, J = 28.7 Hz), 147.7 (d, J = 20.3 Hz); 31P{1H} NMR (CDCl3, 400 MHz): δ 43.7; HRMS m/z (M+H+)
calcd for C25H25O2PH+: 389.1665, found 389.1665; IR (film) νmax: 3340, 2699, 2881, 1458, 1231, 1134, 712, 514
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2-(1-Hydroxybutyl)-1,3-diphenylphosphindole 1-oxide (3o). Purified by flash chromatography (silica gel,
petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid, mp 230.7-232.3 °C, 33.7 mg
(45%); 1H NMR (CDCl3, 400 MHz): δ 0.74 (t, J = 7.6 Hz, 3H), 1.21-1.36 (m, 2H), 1.71-1.92 (m, 1H), 2.05 (s, 1H),
3.39 (s, 1H), 4.53-4.61 (m, 1H), 7.02 (dd, J = 2.7, 7.5 Hz, 1H), 7.28-7.34 (m, 3H), 7.37-7.42 (m, 3H), 7.43-7.50 (m,
4H), 7.57 (t, J = 8.3 Hz, 1H), 7.80 (dd, J = 7.0, 12.7, 2H); 13C{1H} NMR (CDCl3, 400 MHz) δ 13.5, 18.9, 39.0,
69.8 (d, J = 6.6 Hz), 123.7 (d, J = 10.9 Hz), 128.5 (d, J = 37.5 Hz), 128.7 (d, J = 7.3 Hz), 128.8 (d, J = 2.8 Hz),
128.8 (d, J = 9.6 Hz), 129.1 (d, J = 10.8 Hz), 130.9 (d, J = 10.9 Hz), 131.1 (d, J = 100.9 Hz), 131.9 (d, J = 3.5 Hz),
132.2 (d, J = 115.3 Hz), 132.7, 133.5 (d, J = 15.4 Hz), 139.2 (d, J = 93.2 Hz), 143.4 (d, J = 27.1 Hz), 150.6 (d, J =
20.6 Hz); 31P{1H} NMR (CDCl3, 400 MHz): δ 39.3; HRMS m/z (M+H+) calcd for C24H23O2PH+: 375.1508, found
375.1508; IR (film) νmax: 3315, 2927, 2865, 1441, 1187, 1105, 715 cm-1.
2-(1-Hydroxyhexyl)-1,3-diphenylphosphindole 1-oxide (3p). Purified by flash chromatography (silica gel,
petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid, mp 233.5-235.1 °C, 29.0 mg
1
(36%); H NMR (CDCl3, 400 MHz): δ 0.76 (t, J = 6.9 Hz, 3H), 0.99-1.10 (m, 3H), 1.12-1.28 (m, 2H), 1.71-1.89
(m, 2H), 2.01(d, J = 4.8 Hz, 1H), 2.32 (s, 1H), 4.51-4.57 (m, 1H), 7.01 (dd, J = 2.6, 7.5 Hz, 1H), 7.28-7.34 (m, 3H),
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7.37-7.42 (m, 3H), 7.44-7.51 (m, 4H), 7.57 (t, J = 8.3 Hz, 1H), 7.78 (dd, J = 7.3, 12.7, 2H); 13C{1H} NMR (CDCl3,
400 MHz) δ 13.9, 22.4, 25.3, 31.1, 36.9, 70.1 (d, J = 7.0 Hz), 123.7 (d, J = 10.9 Hz), 128.5 (d, J = 33.1 Hz), 128.8
(d, J = 9.6 Hz), 128.8 (d, J = 9.8 Hz), 129.1 (d, J = 10.5 Hz), 130.9 (d, J = 10.9 Hz), 131.1 (d, J = 100.4 Hz), 131.9
(d, J = 2.4 Hz), 132.4 (d, J = 104.6 Hz), 132.7, 133.6 (d, J = 15.2 Hz), 139.3 (d, J = 93.2 Hz), 143.5 (d, J = 27.2
Hz), 150.6 (d, J = 20.7 Hz); 31P{1H} NMR (CDCl3, 400 MHz): δ 39.3; HRMS m/z (M+H+) calcd for C26H27O2PH+:
403.1821, found 403.1830; IR (film) νmax: 3313, 2931, 2857, 1587, 1448, 1203, 1110, 713 cm-1.
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2-(1-Hydroxycyclohexyl)-1,3-diphenylphosphindole 1-oxide (3q). Purified by flash chromatography (silica gel,
petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid, mp 238.2-239.2 °C, 32.0 mg
(40%); 1H NMR (CDCl3, 500 MHz): δ 0.78 (d, J = 12.5 Hz, 1H), 1.23-1.33 (m, 2H), 1.40-1.54 (m, 6H), 1.81 (d, J
= 10.5 Hz, 1H), 2.62 (s, 1H), 6.65 (dd, J = 2.3, 7.5 Hz, 1H), 7.27-7.35 (m, 4H), 7.42-7.48 (m, 4H), 7.49-7.53 (m,
3H), 7.79 (dd, J = 7.0, 12.9 Hz, 2H); 13C{1H} NMR (CDCl3, 500 MHz) δ 21.1, 24.9, 37.6, 38.5, 74.9 (d, J = 7.2
Hz), 123.6 (d, J = 11.1 Hz), 128.3 (d, J = 3.2 Hz), 128.4 (d, J = 6.0 Hz), 128.5 (d, J = 3.4 Hz), 128.6 (d, J = 3.1
Hz), 128.8 (d, J = 8.0 Hz), 128.9 (d, J = 10.5 Hz), 130.8 (d, J = 101.4 Hz), 130.9 (d, J = 10.8 Hz), 131.4 (d, J =
111.7 Hz), 131.9 (d, J = 2.6 Hz), 132.8, 135.1 (d, J = 16.4 Hz), 144.9 (d, J = 122.6 Hz), 145.1 (d, J = 2.7 Hz),
149.0(d, J = 20.8 Hz); 31P{1H} NMR (CDCl3, 500 MHz): δ 42.2; HRMS m/z (M+H+) calcd for C26H25O2PH+:
401.1665, found 401.1665; IR (film) νmax: 3279, 2924, 1186, 1131, 724 cm-1.
2-(1-Hydroxy-2-methoxyethyl)-1,3-diphenylphosphindole 1-oxide (3r). Purified by flash chromatography (silica
gel, petroleum ether/ethyl acetate from 3:1 to 1:1, v/v) to give the desired product: Solid, mp 227.6-228.8 °C, 48.9
mg (65%); 1H NMR (CDCl3, 500 MHz): δ 2.63 (s, 3H), 3.84 (dd, J = 5.0, 7.0 Hz, 1H), 3.95 (dd, J = 5.3, 11.9 Hz,
1H), 3.95 (dt, J = 20.7, 5.1 Hz, 1H), 7.04 (dd, J = 2.8, 7.6 Hz, 1H), 7.30 (s, 2H), 7.37-7.52 (m, 8H), 7.64 (t, J = 8.3,
1H), 7.75 (dd, J = 7.1, 13.1 Hz, 2H); 13C{1H} NMR (CDCl3, 500 MHz) δ 56.3, 64.4, 79.2 (d, J = 6.5 Hz), 124.2 (d,
J = 10.8 Hz), 128.6 (d, J = 12.8 Hz), 129.2, 129.2 (d, J = 9.8 Hz), 129.7 (d, J = 10.8 Hz), 129.7 (d, J = 102.5 Hz),
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131.1 (d, J = 106.1 Hz), 131.3 (d, J = 11.4 Hz), 131.4 (d, J = 29.1 Hz), 132.3 (d, J = 2.7 Hz), 133.2, 134.7 (d, J =
91.9 Hz), 143.9 (d, J = 26.6 Hz), 154.8 (d, J = 20.6 Hz); 31P{1H} NMR (CDCl3, 500 MHz): δ 41.6; HRMS m/z
(M+Na+) calcd for C23H21O3PNa+:399.1121, found 399.1117; IR (film) νmax: 3302, 2820, 1438, 1188, 1132, 710,
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.
N-(2-Hydroxy-2-(1-oxido-1,3-diphenylphosphindol-2-yl)ethyl)acetamide (3s). Purified by flash chromatography
(silica gel, petroleum ether/ethyl acetate from 2:1 to 1:2, v/v) to give the desired product: Solid, mp 243.1-244.3 °C,
32.2 mg (40%); 1H NMR (CDCl3, 500 MHz): δ 1.13 (s, 3H), 3.63 (dd, J = 4.0, 7.8 Hz, 1H), 3.82 (dd, J = 11.8 Hz,
1H), 4.27 (s, 1H), 4.72-4.79 (m, 1H), 6.32 (d, J = 6.9 Hz, 1H), 7.04 (dd, J = 2.8, 4.8 Hz, 1H), 7.24 (d, J = 5.7 Hz,
1H), 7.30-7.34 (m, 1H), 7.41-7.46 (m, 5H), 7.48-7.55 (m, 3H), 7.73-7.77 (m, 2H), 7.92 (d, J = 8.2, 1H); 13C{1H}
NMR (CDCl3, 500 MHz) δ 21.9, 50.8 (d, J = 6.7 Hz), 65.4, 124.4 (d, J = 11.0 Hz), 128.2, 128.9 (d, J = 20.1 Hz),
128.9 (d, J = 10.0 Hz), 129.0 (d, J = 97.4 Hz), 129.1 (d, J = 3.1 Hz), 129.6 (d, J = 11.0 Hz), 130.9 (d, J = 108.1
Hz), 131.0 (d, J = 11.5 Hz), 132.5 (d, J = 2.6 Hz), 132.8 (d, J = 14.5 Hz), 133.5, 135.0 (d, J = 92.9 Hz), 144.3 (d, J
= 26.9 Hz), 153.4 (d, J = 20.5 Hz), 169.8; 31P{1H} NMR (CDCl3, 500 MHz): δ 41.4; HRMS m/z (M+H+) calcd for
C24H22NO2PH+: 404.1410, found 404.1412; IR (film) νmax: 3302, 2820, 1438, 1188, 1132, 710, 515 cm-1.
Procedure for the Synthesis of 3u. In an oven dried Schlenk tube equipped with a magnetic stir bar,
(1,4-phenylenebis(ethyne-2,1-diyl))bis(diphenylphosphine oxide) 1m (105.2 mg, 0.2 mmol), AIBN (9.9 mg, 0.06
mmol, 30 mol %) and TBHP (70% tert-butyl hydroperoxide in water, 128.7 mg, 2.0 mmol, 10 equiv) were mixed
o
in 2a (2 mL) and then stirred at 120 C (in oil bath) for 72 h under air. The mixture was cooled down to room
temperature and purified by flash chromatography (petroleum ether/ethyl acetate from 1:1 to 1:5, v/v) to afford the
corresponding product 3u (51.4 mg, 40% yield).
3,3'-(1,4-Phenylene)bis(2-(2-hydroxypropan-2-yl)-1-phenylphosphindole 1-oxide (3u). Purified by flash
chromatography (silica gel, petroleum ether/ethyl acetate from 1:1 to 1:5, v/v) to give the desired product: Solid,
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mp 256.3-257.9 °C, 51.4 mg (40%); H NMR (CDCl3, 500 MHz): δ 1.12 (s, 6H), 1.25 (s, 6H), 2.62 (s, 2H), 6.68
(dd, J = 1.8, 7.4 Hz, 1H), 6.82 (dd, J = 2.1, 5.4 Hz, 1H), 7.35-7.41 (m, 4H), 7.43-7.47 (m, 8H), 7.54 (t, J = 7.4 Hz,
2H), 7.58-7.63 (m, 2H), 7.77-7.81 (m, 4H); 13C{1H} NMR (CDCl3, 500 MHz) δ 30.9, 31.9 (d, J = 2.0 Hz), 73.5 (d,
J = 6.9 Hz), 123.6 (d, J = 11.1 Hz), 128.4 (d, J = 4.7 Hz), 128.5 (d, J = 10.9 Hz), 128.7 (d, J = 2.7 Hz), 128.9 (d, J
= 8.9 Hz), 129.0 (d, J = 10.4 Hz), 130.8 (d, J = 100.7 Hz), 130.9, 131.1 (d, J = 11.0 Hz), 132.5 (d, J = 99.2 Hz),
134.9 (d, J = 17.4 Hz), 144.1, 145.1 (d, J = 3.5 Hz), 145.2 (d, J = 28.2 Hz), 148.7 (d, J = 20.3 Hz); 31P{1H} NMR
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(CDCl3, 500 MHz): δ 41.9; HRMS m/z (M+H+) calcd for C40H36O4P2H+: 643.2162, found 643.2165; IR (film) νmax
:
3312, 1452, 1178, 1125, 712, 514 cm-1.
General Procedure for the Synthesis of 6H-indeno[2,1-b]phosphindole 5-oxide 4a-4j. In an oven dried Schlenk
tube equipped with a magnetic stir bar, diaryl(arylethynyl) phosphine oxide 1 (0.2 mmol), AIBN (4.9 mg, 0.03
mmol, 15 mol %) and TBHP (70% tert-butyl hydroperoxide in water, 128.7 mg, 1.0 mmol, 5 equiv) were mixed in
o
2 (2 mL) and then stirred at 120 C (in oil bath) for 36 h under air. The mixture was cooled down to room
temperature and solvent was removed under vacuum for
1
hour. Afterwards HFIP
(1,1,1,3,3,3-hexafluoro-2-propanol, 1 mL) and trifluoromethanesulfonic acid (15.0 mg, 0.1 mmol, 50 mol %) were
added and stirred at 90 oC for another 24 hours under air. The mixture was cooled down to room temperature and
purified by flash chromatography (petroleum ether/ethyl acetate from 5:1 to 3:1, v/v) to afford the corresponding
products.
6,6-Dimethyl-5-phenyl-6H-indeno[2,1-b]phosphindole 5-oxide (4a). Purified by flash chromatography (silica
gel, petroleum ether/ethyl acetate from 5:1 to 3:1, v/v) to give the desired product: Solid, mp 231.7-232.2 °C, 54.7
mg (80%); 1H NMR (CDCl3, 400 MHz): δ 1.10 (s, 3H), 1.62 (s, 3H), 7.35-7.43 (m, 6H), 7.48 (td J = 1.6, 7.3 Hz,
1H), 7.55-7.63 (m, 2H), 7.74 (dd, J = 7.1, 12.9 Hz, 2H), 7.90-7.93 (m, 2H); 13C{1H} NMR (CDCl3, 400 MHz) δ
25.1 (d, J = 17.4 Hz), 49.6 (d, J = 9.9 Hz), 122.4 (t, J = 4.5 Hz), 127.1 , 128.5 (d, J = 78.6 Hz), 128.7 (d, J = 12.6
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Hz), 129.1 (d, J = 11.4 Hz), 129.6 (d, J = 10.0 Hz), 129.8 (d, J = 103.4 Hz), 131.1 (d, J = 11.0 Hz), 132.1 (d, J =
2.7 Hz), 132.6, 135.9 (d, J = 15.3 Hz), 138.4 (d, J = 20.0 Hz), 138.5 (d, J = 107.1 Hz), 148.5 (d, J = 104.1 Hz),
154.5 (d, J = 24.4 Hz), 160.0 (d, J = 8.7 Hz); 31P{1H} NMR (CDCl3, 400 MHz): δ 27.0; HRMS m/z (M+H+) calcd
for C23H19OPH+: 343.1246, found 343.1246; IR (film) νmax: 3211, 2598, 1448, 1355, 701, 525 cm-1.
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6,6,8-Trimethyl-5-phenyl-6H-indeno[2,1-b]phosphindole 5-oxide (4b). Purified by flash chromatography (silica
gel, petroleum ether/ethyl acetate from 5:1 to 3:1, v/v) to give the desired product: Solid, mp 234.6-236.2 °C, 42.7
mg (60%); δ 1H NMR ( CDCl3, 400 MHz): δ 1.08 (s, 3H), 1.60 (s, 3H), 2.44 (s, 3H), 7.21-7.22 (m, 2H), 7.32-7.39
(m, 3H), 7.46 (td, J = 1.4, 7.6 Hz, 1H), 7.52-7.62 (m, 2H), 7.71-7.80 (m, 3H), 7.91 (dd, J = 3.3, 7.6 Hz, 1H);
13C{1H} NMR (CDCl3, 500 MHz) δ 21.9, 25.2 (d, J = 14.9 Hz), 49.4 (d, J = 10.0 Hz), 122.1, 122.4 (d, J = 9.3 Hz),
123.1 (d, J = 1.8 Hz), 127.9, 128.7 (d, J = 13.6 Hz), 129.1 (d, J = 11.0 Hz), 129.6 (d, J = 11.0 Hz), 131.2 (t, J =
11.1 Hz), 132.4 (d, J = 48.0 Hz), 133.3 (d, J = 14.9 Hz), 138.5 (d, J = 20.3 Hz), 138.7, 139.1, 160.4 (d, J = 8.8 Hz);
31P{1H} NMR (CDCl3, 400 MHz): δ 27.3; HRMS m/z (2M+Na+) calcd for C48H42O2P2Na+:735.2252, found
735.2551; IR (film) νmax: 3255, 2692, 2598, 1432, 1361, 711 cm-1.
8-(Tert-butyl)-6,6-dimethyl-5-phenyl-6H-indeno[2,1-b]phosphindole 5-oxide (4c). Purified by flash
chromatography (silica gel, petroleum ether/ethyl acetate from 5:1 to 3:1, v/v) to give the desired product: Solid,
1
mp 234.2-236.1 °C, 51.0 mg (64%); H NMR (CDCl3, 500 MHz): δ 1.11 (s, 3H), 1.38 (s, 9H), 1.63 (s, 3H),
7.35-7.39 (m, 3H), 7.42 (d, J = 1.6 Hz, 1H), 7.45 (d, J = 1.7 Hz, 1H), 7.47 (d, J = 1.8 Hz, 1H), 7.54-7.63 (m, 2H),
7.71-7.76 (m, 2H), 7.85 (d, J = 8.1 Hz, 1H), 7.89 (dd, J = 3.3, 7.5Hz, 1H); 13C{1H} NMR (CDCl3, 500 MHz) δ
25.3, 31.6, 49.6 (d, J = 9.8 Hz), 119.1, 121.8, 122.3 (d, J = 9.1 Hz), 124.3, 128.7 (d, J = 12.6 Hz), 129.1 (d, J =
11.3 Hz), 129.6 (d, J = 10.0 Hz), 129.9 (d, J = 104.7 Hz), 131.1 (d, J = 11.0 Hz), 132.0 (d, J = 3.6 Hz), 132.5,
133.2 (d, J = 15.3 Hz), 138.4 (d, J = 20.4 Hz), 138.6 (d, J = 107.4 Hz), 148.9 (d, J = 105.2 Hz), 152.0, 154.5 (d, J
= 24.2 Hz), 160.6 (d, J = 9.0 Hz); 31P{1H} NMR (CDCl3, 500 MHz): δ 27.2; HRMS m/z (M+Na+) calcd for
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C27H27OPNa+: 421.1692, found 421.1703; IR (film) νmax: 3209, 2872, 2587, 1445, 1338, 714, 511 cm-1.
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8-Methoxy-6,6-dimethyl-5-phenyl-6H-indeno[2,1-b]phosphindole
5-oxide
(4d).
Purified
by
flash
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chromatography (silica gel, petroleum ether/ethyl acetate from 5:1 to 3:1, v/v) to give the desired product: Solid,
mp 228.3-229.2°C, 44.7 mg (60%); 1H NMR (CDCl3, 500 MHz): δ 1.00 (s, 3H), 1.46 (s, 3H), 3.88 (s, 3H), 6.88 (d,
J = 2.3 Hz, 1H), 6.94 (dd, J = 2.3, 8.4 Hz, 1H), 7.15 (s, 1H), 7.29-7.33 (m, 2H), 7.42-7.47 (m, 3H), 7.70-7.78 (m,
3H), 7.78 (d, J = 8.4 Hz, 1H); 13C{1H} NMR (CDCl3, 500 MHz) δ 25.2 (d, J = 21.3 Hz), 49.4 (d, J = 9.9 Hz), 55.6,
108.6, 112.4, 122.2 (d, J = 9.3 Hz), 123.1, 128.7 (d, J = 12.8 Hz), 129.1 (d, J = 11.5 Hz), 129.8 (d, J = 10.2 Hz),
131.2 (d, J = 11.2 Hz), 132.1 (d, J = 2.6 Hz), 132.5, 132.5, 138.2 (d, J = 20.9 Hz), 154.9, 160.5, 162.5 (d, J = 9.2
Hz); 31P{1H} NMR (CDCl3, 500 MHz): δ 27.7; HRMS m/z (2M+Na+) calcd for C48H42O4P2Na+: 767.2451, found
767.2451; IR (film) νmax: 3235, 2850, 2611, 1452, 1367, 718, 514 cm-1.
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8-Fluoro-6,6-dimethyl-5-phenyl-6H-indeno[2,1-b]phosphindole 5-oxide (4e). Purified by flash chromatography
(silica gel, petroleum ether/ethyl acetate from 5:1 to 3:1, v/v) to give the desired product: Solid, mp 235.2-236.8 °C,
1
52.6 mg (73%); H NMR (CDCl3, 500 MHz): δ 1.11 (s, 3H), 1.64 (s, 3H), 7.40-7.43 (m, 5H), 7.52 (t, J = 7.4 Hz,
1H), 7.60 (t, J = 7.6 Hz, 1H), 7.65 (dd, J = 2.8, 7.5 Hz, 1H), 7.75 (dd, J = 5.7, 7.3 Hz, 2H), 7.84-7.88 (m, 2H);
13C{1H} NMR (CDCl3, 500 MHz) δ 25.1 (d, J = 25.6 Hz), 49.8 (d, J = 9.9 Hz), 122.4 (d, J = 10.1 Hz), 123.1 (d, J
= 1.8 Hz), 123.2, 127.5, 128.9 (d, J = 12.5 Hz), 129.4 (d, J = 11.2 Hz), 129.7 (d, J = 103.7 Hz), 129.9 (d, J = 10.1
Hz), 131.2 (d, J = 11.0 Hz), 132.3 (d, J = 2.5 Hz), 132.7, 132.5 (d, J = 21.1 Hz), 134.6, 138.1 (d, J = 19.6 Hz),
138.5 (d, J = 97.2 Hz), 150.4 (d, J = 92.3 Hz), 153.5 (d, J = 24.1 Hz), 161.8 (d, JC-F = 231.5 Hz); 31P{1H} NMR
(CDCl3, 500 MHz): δ 26.5; HRMS m/z (M+H+) calcd for C23H18OPH+: 361.1158, found 361.1162; IR (film) νmax
:
3261, 2641, 1467, 1392, 739, 521 cm-1.
8-Chloro-6,6-dimethyl-5-phenyl-6H-indeno[2,1-b]phosphindole 5-oxide (4f). Purified by flash chromatography
(silica gel, petroleum ether/ethyl acetate from 5:1 to 3:1, v/v) to give the desired product: Solid, mp 232.5-233.1 °C,
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62.4 mg (83%); 1H NMR (CDCl3, 500 MHz): δ 1.08 (s, 3H), 1.61 (s, 3H), 7.37-7.41 (m, 5H), 7.49 (td, J = 7.3, 1.4
Hz, 1H), 7.55-7.63 (m, 2H), 7.72 (dd, J = 7.0, 13.0 Hz, 2H), 7.80-7.85 (m, 2H); 13C{1H} NMR (CDCl3, 500 MHz)
δ 24.9 (d, J = 26.0 Hz), 49.7 (d, J = 9.9 Hz), 122.3 (d, J = 9.1 Hz), 123.0 (d, J = 1.6 Hz), 123.1, 127.4 , 128.8 (d, J
= 12.7 Hz), 129.3 (d, J = 11.4 Hz), 129.5 (d, J = 103.6 Hz), 129.8 (d, J = 10.1 Hz), 131.1 (d, J = 11.0 Hz), 132.2 (d,
J = 3.6 Hz), 132.6 (d, J = 1.8 Hz), 134.4 (d, J = 15.4 Hz), 134.5, 137.9 (d, J = 20.0 Hz), 138.4 (d, J = 107.0 Hz),
150.2 (d, J = 103.7 Hz), 153.4 (d, J = 25.4 Hz), 161.7 (d, J = 9.1 Hz); 31P{1H} NMR (CDCl3, 500 MHz): δ 26.6;
HRMS m/z (M+H+) calcd for C23H18OPH+: 377.0857, found 377.0857; IR (film) νmax: 3252, 2634, 1459, 1387,
731, 521 cm-1.
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8-Bromo-6,6-dimethyl-5-phenyl-6H-indeno[2,1-b]phosphindole 5-oxide (4g). Purified by flash chromatography
(silica gel, petroleum ether/ethyl acetate from 5:1 to 3:1, v/v) to give the desired product: Solid, mp 235.2-236.8 °C,
65.5 mg (78%); 1H NMR (CDCl3, 400 MHz): δ 1.07 (s, 3H), 1.60 (s, 3H), 7.36-7.41 (m, 3H), 7.49 (td, J = 7.2, 1.3
Hz, 1H), 7.53-7.63 (m, 4H), 7.70-7.77 (m, 3H), 7.84 (dd, J = 3.3, 7.5 Hz, 1H); 13C{1H} NMR (CDCl3, 400 MHz) δ
24.9 (d, J = 28.0 Hz), 49.8 (d, J = 9.9 Hz), 122.3 (d, J = 9.3 Hz), 122.8, 123.4, 127.4 , 125.9 (d, J = 1.50 Hz), 128.8
(d, J = 12.7 Hz), 129.3 (d, J = 11.4 Hz), 129.8 (d, J = 10.0 Hz), 130.3, 131.1 (d, J = 12.0 Hz), 132.3 (d, J = 2.3 Hz),
132.7, 134.8 (d, J = 15.4 Hz), 138.0, 138.3 (d, J = 107.8 Hz), 150.1 (d, J = 103.6 Hz), 153.6 (d, J = 24.3 Hz), 161.8
(d, J = 9.6 Hz); 31P{1H} NMR (CDCl3, 500 MHz): δ 26.9; HRMS m/z (M+Na+) calcd for C23H18BrOPNa+:
443.0171, found 443.0180; IR (film) νmax: 3258, 2641, 1464, 1395, 741, 525 cm-1
.
6,6-Dimethyl-5-phenyl-8-(trifluoromethyl)-6H-indeno[2,1-b]phosphindole 5-oxide (4h). Purified by flash
chromatography (silica gel, petroleum ether/ethyl acetate from 5:1 to 3:1, v/v) to give the desired product: Solid,
mp 237.2-239.0 °C, 63.2 mg (77%); 1H NMR (CDCl3, 400 MHz): δ 1.13 (s, 3H), 1.67 (s, 3H), 6.03-6.08 (m, 1H),
7.39-7.44 (m, 3H), 7.51 (td, J = 7.4, 1.2 Hz, 1H), 7.60-7.67 (m, 2H), 7.71-7.75 (m, 2H), 7.91 (dd, J = 3.3, 7.6 Hz,
1H), 8.09 (d, J = 1.2 Hz, 1H), 8.20 (dd, J = 1.5, 8.0 Hz, 1H); 13C{1H} NMR (CDCl3, 500 MHz) δ 24.8 (d, J = 34.2
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Hz), 50.1 (d, J = 9.7 Hz), 67.2 (d, J = 34.6 Hz), 122.6 (t, J = 4.8 Hz), 124.0 (q, J = 1.7 Hz), 126.0, 129.0 (d, J =
12.7 Hz), 129.1 (d, J = 104.4 Hz), 129.7 (d, J = 11.3 Hz), 130.2 (t, J = 4.7 Hz), 131.2 (d, J = 11.0 Hz), 132.6 (d, J
= 2.6 Hz), 133.0, 137.7, 138.2 (d, J = 89.0 Hz), 142.2 (d, J = 15.1 Hz), 153.0 (d, J = 24.3 Hz), 154.9 (d, J = 101.3
Hz), 160.3 (d, J = 9.1 Hz), 163.4; 31P{1H} NMR (CDCl3, 400 MHz): δ 26.1; HRMS m/z (2M+Na+) calcd for
C48H36F6O2P2Na+: 843.1987, found 843.1986; IR (film) νmax: 3240, 2618, 1471, 1377, 1142, 723, 513 cm-1.
6,6-Diethyl-5-phenyl-6H-indeno[2,1-b]phosphindole 5-oxide (4i). Purified by flash chromatography (silica gel,
petroleum ether/ethyl acetate from 5:1 to 3:1, v/v) to give the desired product: Solid, mp 242.2-244.1 °C, 40.7 mg
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(55%); H NMR (CDCl3, 400 MHz): δ -0.02 (t, J = 7.4 Hz, 3H), 0.69 (t, J = 7.4 Hz, 3H), 155-1.59 (m, 1H),
1.70-1.74 (m, 1H), 1.96-2.02 (m, 1H), 2.24-2.28 (m, 1H), 7.27-7.29 (m, 1H), 7.34-7.40 (m, 5H), 7.47 (td, J = 7.3,
1.4 Hz, 1H), 7.59 (t, J = 7.7 Hz, 1H), 7.63-7.67 (m, 1H), 7.70-7.74 (m, 2H), 7.89-7.92 (m, 2H); 13C{1H} NMR
(CDCl3, 500 MHz) δ 8.3, 9.0, 30.6, 31.1, 59.6 (d, J = 9.7 Hz), 122.2, 122.2 (d, J = 9.4 Hz), 122.7 (d, J = 1.7 Hz),
126.9, 128.0, 128.6 (d, J = 12.6 Hz), 129.1 (d, J = 11.1 Hz), 129.9 (d, J = 10.0 Hz), 130.1 (d, J = 104.0 Hz), 131.2
(d, J = 11.0 Hz), 132.2 (d, J = 2.7 Hz), 137.9 (d, J = 107.3 Hz), 138.2 (d, J = 15.4 Hz), 138.7 (d, J = 20.5 Hz),
146.8 (d, J = 102.9 Hz), 156.4 (d, J = 10.1 Hz), 156.5 (d, J = 6.2 Hz), 173.4; 31P{1H} NMR (CDCl3, 500 MHz): δ
28.3; HRMS m/z (M+H+) calcd for C25H23OPH+: 371.1559, found 371.1559; IR (film) νmax: 3224, 2843, 2607,
1462, 1364, 714, 526 cm-1
.
5'-Phenylspiro[cyclohexane-1,6'-indeno[2,1-b]phosphindole] 5'-oxide (4j). Purified by flash chromatography
(silica gel, petroleum ether/ethyl acetate from 5:1 to 3:1, v/v) to give the desired product: Solid, mp 251.6-252.1 °C,
29.0 mg (38%); 1H NMR (CDCl3, 500 MHz): δ 0.90-1.05 (m, 1H), 1.23-1.28 (m, 1H), 1.32-1.45 (m, 2H),
1.68-1.72 (m, 2H), 1.77-1.81 (m, 2H), 2.08 (d, J = 22.1 Hz, 2H), 7.24-7.28 (m, 1H), 7.34-7.38 (m, 2H), 7.43-7.52
(m, 5H), 7.59 (td, J = 7.5, 2.6 Hz, 1H), 7.74-7.78 (m, 2H), 7.59 (dd, J = 2.9, 4.5 Hz, 1H), 7.95-7.97 (m, 1H);
13C{1H} NMR (CDCl3, 500 MHz) δ 20.9, 23.4, 24.3, 25.3, 37.8, 35.7, 56.2 (d, J = 8.6 Hz), 122.3 (d, J = 10.0 Hz),
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