Synthesis of C2-Phosphorylated Indoles via Metal-Free 1,2-Phosphorylation of 3-Indolylmethanols with P(O)-H Species

Article abstract of DOI:10.1002/adsc.201900987

An efficient and practical method for synthesis of C2-phosphorylated indoles has been disclosed via a metal-free 1,2-phosphorylation of 3-indolylmethanols with H-phosphine oxides or H-phosphonates. This alternative protocol features a broad substrate scope with respect to both 3-indolylmethanols derived from isatins, acyclic α-keto amide, α-keto ester, 1,2-diketone and simple ketones and H-phosphine oxides or H-phosphonates, moderate to high yields and mild reaction conditions. Mechanistic studies indicate that this reaction proceeds via an unusual direct 1,2-addition pathway, in which the existence of an electron-withdrawing group adjacent to the hydroxyl group of 3-indolylmethanols plays a decisive role. (Figure presented.).

Full text of DOI:10.1002/adsc.201900987

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DOI: 10.1002/adsc.201900987
Synthesis of C2-Phosphorylated Indoles via Metal-Free 1,2-
Phosphorylation of 3-Indolylmethanols with P(O)-H Species
Yun-Xiang Zou,a Xiao-Yan Liu,a Jing Zhang,a Hong-Li Yang,a Xin-Yue Yang,a
Xiao-Ling Liu,a Yi-Wen Chu,a and Long Chena,*
a
Antibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics,
Chengdu University, 168 Hua Guan Road, Chengdu 610052, People’s Republic of China
E-mail: chenlong@cdu.edu.cn
Manuscript received: August 7, 2019; Revised manuscript received: September 30, 2019;
Version of record online: ■■■, ■■■■
Supporting information for this article is available on the WWW under https://doi.org/10.1002/adsc.201900987
disclosed an efficient rhodium-catalyzed pyrimidine-
Abstract: An efficient and practical method for
synthesis of C2-phosphorylated indoles has been
disclosed via a metal-free 1,2-phosphorylation of 3-
indolylmethanols with H-phosphine oxides or H-
directed CÀ H activation/phosphonylation of indoles to
obtain C2-phosphonylated indoles (eq 2, Scheme 2).[6]
However, these impressive advances still have some
drawbacks, such as the requirement of stoichiometric
phosphonates. This alternative protocol features a
amount of metal catalysts or oxidants[5a–c] and/or
broad substrate scope with respect to both 3-
expensive photoredox catalysts.[5d,e] Recently, Gao and
indolylmethanols derived from isatins, acyclic α-
Xu reported an efficient acid-catalyzed three compo-
keto amide, α-keto ester, 1,2-diketone and simple
nent reaction of indoles, H-phosphine oxides and
ketones and H-phosphine oxides or H-phosphonates,
ketones for the synthesis of C2-phosphinoylated
moderate to high yields and mild reaction condi-
indoles, in which they proposed a tandem Pudovik/
tions. Mechanistic studies indicate that this reaction
Friedel-Crafts reaction/1,3-P migration sequence for
proceeds via an unusual direct 1,2-addition pathway,
in which the existence of an electron-withdrawing
this reaction (eq 3, Scheme 1).[7] Yet, the features of
high reaction temperature, Ar atmosphere and limited
group adjacent to the hydroxyl group of 3-indolyl-
substrate generality should be further addressed. There-
methanols plays a decisive role.
fore, the development of novel metal-free protocols
leading to C2-phosphorylated indoles under mild
Keywords: 3-Indolylmethanols; Phosphorylated in-
conditions still remains urgent and highly desirable.
doles; 1,2-addition; Phosphorylation; Metal-free
Recently, 3-indolylmethanols have distinguished
themselves to be versatile synthons for accessing
diverse indole derivatives.[8,9] Under the Lewis or
As one of the most fascinating indole derivatives,[1,2] Brønsted acid catalysis, 3-indolylmethanols could be
phosphorus-containing indoles have gained great atten- readily transformed to carbocation and vinyliminium
tion from the organic community for their wide intermediates, which have a great tendency to undergo
applications in pharmaceuticals, agricultural chemicals 1,4-additions with various C-based nucleophiles to
and materials.[3] Particularly, C2-phosphorylated indole afford C3-functionalized indoles.[9] However, the 1,2-
derivatives show important values in synthetic and additions of this intermediate have been rarely reported
medicinal chemistry and material science.[4] As a despite this process could enable the formation of C2-
result, various approaches have been established to functionalized indoles.[10] The Shi’s group reported two
access such frameworks.[3] The direct C2-phosphoryla- examples of formal synthesis of C2-functionalized
tion of indole skeleton is one of the most important indoles via 1,4-addition initiated tandem reactions of
strategies, which has attracted considerable attention. isatin-derived 3-indolylmethanols.[10e,f] As more than
In this context, transition-metal and visible light photo- two steps are needed in both reactions, the overall
redox catalysis have presented their power in the yields of most cases are moderate. What’s more,
construction of C2-phosphorylated indoles through generally more than 12 hours were needed with heating
°
radical oxidative dehydrogenative coupling reactions conditions (50–55 C). Thus, we wondered if it was
between indoles and P(O)-H species (eq 1, possible to improve the yield of C2-functionalized
Scheme 1).[5] On the other hand, the group of Hong indoles from 3-indolylmethanols through developing
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Initially, we started our investigation by performing
the model reaction of N-benzyl isatin-derived 3-indolyl-
methanol 1a and Ph2P(O)H (2a) under open-air in the
presence of 10 mol% of HOTf (trifluoromethanesulfonic
°
acid) in DCE (ClCH2CH2Cl) at 25 C. To our delight, the
anticipated 1,2-addition product C2-phosphinoylated
indole 3a was obtained albeit in only 39% yield (entry 1,
table S1). The structure of 3a was unambiguously
determined by NMR, HRMS and further confirmed by
single-crystal X-ray diffraction analysis.[13] To improve
the efficiency, we continued to evaluate other reaction
parameters such as acid catalysts,[14,15] solvents, additives,
catalyst loading and the ratio of 1a and 2a, and finally
established the optimal reaction condition as follows:
°
25 C under air using 10 mol% of (�)-CSA as catalyst in
DCE (entry 4, table S1, Scheme 2). It should be noted
that the reaction could not proceed at all in the absence
of acid catalyst.
To demonstrate the practicable of current method,
we first tried the preparative scale synthesis of 3a by
running 1 mmol scale reaction using the optimal
condition and found 81% yield was obtained for 3a
(entry 4, table S1). We next checked other types of 3-
indolylmethanols (Scheme 3). Pleasantly, 3-indolylme-
thanols 4a–4d derived from acyclic α-keto amide, α-
keto ester, 1,2-diphenylketone and 2,2,2-trifluoro-1-
phenylethan-1-one could smoothly participate in this
reaction furnishing the desired 1,2-addition products
5a–5d in 84–90% yields. Unfortunately, 3-indolylme-
thanol 4e failed to react with 2a to give 5e, possibly
because 4e underwent elimination reaction under this
condition. And substrate 4f decomposed quickly under
current condition. Unexpectedly, the reactions of 3-
indolylmethanols 4g–4j with 2a gave the 1,4-addition
Scheme 1. Routes to C2-phosphorylated indoles.
Scheme 2. Synthesis of 3a from 1a and 2a.
the direct 1,2-additions of 3-indolylmethanols. How- adducts 6a–6d as the sole products (for possible
ever, to the best of our knowledge, neither have the reasons, see Scheme 5). After some conditions screen-
reaction of other nucleophiles such as P(O)-H species
with 3-indolymethanols been investigated, nor have
any processes been reported involve the direct 1,2-
additions of 3-indolylmethanols.
With continuous interest in the construction of CÀ P
bonds[11] via dehydrative coupling between alcohols
and P(O)-H species,[12] we detailed our findings herein
on the above-mentioned aspects by exploring the
reaction of 3-indolylmethanols with P(O)-H com-
pounds (eq 4, Scheme 1). Interestingly, the reaction
proceeded smoothly in the presence of (�)-CSA
°
(camphorsulfonic acid) at 25 C, tolerating broad scope
of 3-indolylmethanols and P(O)-H compounds to
furnish the desired C2-phosphorylated indoles in
moderate to high yields. Particularly, mechanistic
studies suggest that such products come from the direct
1,2-phosphorylation of the vinyliminium intermediate
derived from 3-indolylmethanols, which fills the gap
of direct 1,2-addition pathway in 3-the indolylmetha-
Scheme 3. Results with respect to other types of 3-indolylme-
thanols.
nol-involved reaction modes.
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ing, it was found that running the reaction of 4g and methanols could also be amenable to this reaction
°
2a using HOTf as catalyst in CH3CN at 100 C for affording 3k–3m in 68–78% yields. Besides, a serious of
24 h[12b] could allow the formation of 1,2-adduct 5g substrates with different R2 groups at different positions
from intermediate 6a. However, when 4h–4j were of the indole moiety could also be successfully altered,
subjected to this process, only trace amount of C2- leading to C2-phosphinoylation of 3-indolylmethanols in
phosphorylated indoles was generated. Nevertheless, overall good yields. It seemed that the electronic nature
the success in obtaining products 5g and 3- of the R2 substituents had no obvious effect on the
(phosphoryl)methylindoles 6a–6d from 3-indolylme- reaction, because there was no significant difference
thanols derived from diarylketones could serve as a between electron-donating and withdrawing groups in
good complement to the Xu’s method.[7]
terms of reaction time and yields (3n–3s). In addition,
Given the importance of oxindole-containing scaffolds N-methyl protected substrate could be also tolerated (3t),
in medicinal chemistry, we next examined the generality which indicated that the indole NÀ H group was not
of isatin-derived 3-indolylmethanols containing different crucial. During the further examnination of other sub-
R1/R2/R3/R4 groups (Table 1). Gratifyingly, the reaction stituents on the indole framework,[16] we found the
proceeded smoothly and afforded the desired C2- reaction of 3-indolylmethanol (1u) that derived from N-
°
phosphinoylated indoles 3 in generally good yields within Boc protected indole did not proceed at rt and even 80 C
30 minutes to 25.0 hours. In detail, various N-benzyl- for 24 h possibly due to the strong electron-withdrawing
isatin-derived 3-indolylmethanols bearing either electron- Boc group resulting in the difficulty in the formation of
donating or withdrawing R1 groups at the C4, C5 and C7 carbocation from 1u (for details, see Supporting
positions of the isatin moiety could participate in this Information).
reaction well to generate products 3a–3j. Remarkably, a
Isatin-derived 3-Indolylmethanol 1a was then chosen
significant steric effect could be observed as exemplified to evaluate the scope of disubstituted phosphine oxides or
by the fact 3-indolylmethanols with a bromo substituent H-phosphonates (Table 2). Diarylphosphine oxides with
at the C4 position gave inferior results (more reaction electron-donating groups including methyl, methoxyl, i-
time needed for 3b and 3j) to those with substituents at propyl and n-butyl at the ortho or para position of the
C5 position (3c–3h), while 3-indolylmethanols with
substituents at the C7 position furnished higher yields for
3i. N-methyl, N-phenyl and particular N-free 3-indolyl-
Table 2. Scope of di-substituted P(O)-H species.[a,b]
Table 1. Scope of isatin-derived 3-indolylmethanols.[a,b]
[a] Reaction conditions: 1 (0.36 mmol), 2a (0.3 mmol), (�)-
[a] Reaction conditions: 1a (0.36 mmol), 2 (0.3 mmol), (�)-
°
°
CSA (0.03 mmol), ClCH2CH2Cl (3.0 mL), stirred at 25 C
CSA (0.03 mmol), ClCH2CH2Cl (3.0 mL), stirred at 25 C
under air atmosphere.
under air atmosphere.
[b] Isolated yield.
[b] Isolated yield.
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phenyl ring gave products 3u–3v and 3x–3y in (�)-CSA or HOTf as catalyst. In fact, 7a could not be
°
°
moderate to good yields (48–71%). Substrates with converted to 3a at 25 C and even 80 C (eq 2,
electron-withdrawing bromo or chloro substituent seemed Scheme 4). In addition, 3a could not also be trans-
to afforded higher yields for 3w and 3z. 2-Naphthyl and formed to 7a under the same conditions (eq 3,
2-thienyl substituted phosphine oxides were also compat- Scheme 4). These results greatly indicated that 3a
ible, giving 3zb and 3zc in 78% and 62% yield, derived from the direct 1,2-addition rather than the
respectively. Compared to diarylphosphine oxides, di transformation of 1,4-addition adduct 7a under current
(benzyl)phosphine oxide showed lower reactivity, thus conditions. The low yield of 3a when using HOTf or
affording product 3zd in only 35% yield. Besides HClO4 as catalyst (entry 1 and 2, table S1) possibly
symmetric disubstitued phosphine oxides, unsymmetric resulted from the rapid decomposition of isatin-derived
phenyl benzyl H-phosphine oxide was also effective for 3-indolylmethanols under strong acids conditions,
this transformation, giving product 3ze as a single isomer because many polar unidentified complexes were
in 43% yield. Apart from phosphine oxides, symmetric produced when exposing 1a under HOTf conditions.
H-phosphonates were also examined, and the correspond- (for details, see SI) Subsequent radical trapping experi-
ing products 3zf–3zk were successfully obtained in ment using BHT (2,6-di-tert-butyl-4-methylphenol)
lower yields albeit with full conversion of 1, possibly due unaffecting the reaction together with reactions with
to the lower nucleophilicity of these phosphorus BHT or 4-bromophenol alone resulting in trace amount
nucleophiles.[15] Cyclic 4,4-dimethyl-1,3,2-dioxaphospho- of 3a (eq 4, Scheme 4) indicated that a radical
lane 2-oxide also gave the corresponding product 3zk in mechanism was not involved in this reaction.
relatively higher yield than that of symmetric H-
According to the control experiments and previous
phosphonates (3zg–3zj) with higher nucleophilicity. The reports,[8,10e,f] a possible reaction pathway was suggested
reason for this observed unusual phenomenon is still for the formation of C2-phosphorylated indoles from 3-
unknown.
indolylmethanols and P(O)-H species (Scheme 5). Under
In order to gain some insights into the formation of the catalysis of (�)-CSA or HOTf, 3-indolylmethanols 1
C2-phosphorylated indoles from 3-indolylmethanols, or 4 were easily transformed to their reactive resonant
several control experiments were conducted hybrids of carbocations I and II, vinyliminium, and
(Scheme 4). When the model reaction was carried out delocalized cation intermediates. The electron nature of
in the presence of 10 mol% of HOTf, apart from the R1 and R2 groups played an important role in the
1,2-addition product 3a, the 1,4-addition adduct 7a subsequent regioselectivity of trapping I or II by 2a. In
was also observed albeit in only 10% yield (eq 1, detail, when R1 and R2 were aryl groups, the generation
Scheme 4). According to our[12b] and Xu’s work,[7] we of carbocation I was preferential as it could be stabilized
wondered if 3a came from the transformation of 1,4- by these two aryl groups. In this case, I was attacked by
addition adduct 7a via a [1,3]-P migration process. For 2a thus giving the normal 1,4-addition products 6 that
the aim to confirm 3a came from 7a or the direct 1,2- might be further converted to the 1,2-addition adducts
addition, 7a was subjected to reaction conditions using (for 5g) via a reported 1,3-P migration.[7,12b] As we can
see here, the formation of 5g involved 1,4-addition and
sequential 1,3-P migration process, in which at least 96%
yield of intermediate 6a was obtained in the first 1,4-
additon step but the hard conversion of 6a to 5g
decreased the overall yield (30% yield for two steps).
This evidence further demonstrated the priority of direct
1,2-additions to 1,4-addition initiated tandem reactions in
the synthesis of C2-functionlized indoles from 3-
Scheme 4. Preliminary mechanistic studies.
Scheme 5. Suggested possible reaction pathway.
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The reaction was carried out under an air atmosphere. To a 10-mL
vial were added isatin-derived 3-indolylmethanols 1 or 4 (4a–4d)
(0.36 mmol, 1.2 equivs), R5R6P(O)H 2 (0.3 mmol, 1.0 equiv) and
(�)-CSA (7.0 mg, 10 mol%). After adding 3.0 mL of anhydrous
°
ClCH2CH2Cl, the reaction mixture was stirred at 25 or 60 C till
almost full conversion of 2 by TLC analysis. The reaction mixture
was directly subjected to column chromatography using petrol
ether/ethyl acetate (generally 2:1 to 1:1, v:v) or dichloromethane/
ethyl acetate (generally 10:1 to 5:1, v:v) as the eluent to afford C2-
phosphorylated indoles 3 or 5.
1-benzyl-3-(2-(diphenylphosphoryl)-1H-indol-3-yl)indolin-2-
°
one (3a). White solid, 142.0 mg, 88% yield; Mp: 234–236 C;
1H NMR (600 MHz, CDCl3): δ=9.71 (s, 1H), 8.11–8.07 (m,
2H), 7.86–7.82 (m, 2H), 7.62-7.61 (m, 1H), 7.58–7.53 (m, 3H),
7.48-7.46 (m, 2H), 7.40-7.39 (m, 2H), 7.37–7.36 (m, 1H), 7.34–
7.29 (m, 3H), 7.14–7.12 (m, 2H), 6.84–6.82 (m, 1H), 6.79 (t,
J=7.8 Hz, 1H), 6.72 (t, J=7.8 Hz, 1H), 6.58–6.57 (m, 1H),
6.49–6.48 (m, 1H), 5.16 (AB, J=18.0 Hz, 1H), 4.80 (s, 1H),
4.78 (AB, J=18.0 Hz, 1H); 13C{1H} NMR (150 MHz, CDCl3):
Scheme 6. Product elaboration.
indolylmethanols to some extent. In case of 3-indolylme-
thanols bearing an electron-withdrawing group adjacent
to the hydroxyl moiety, the delocalized carbocation
tended to form carbocation II, which was further trapped
δ=175.8, 142.7, 138.0 (d, JC-P =9.0 Hz), 135.8, 132.9 (d, JC-P
=
by 2a thus furnishing the direct 1,2-addition product 3 or 109.5 Hz), 132.7, 132.4 (d, JC-P =10.5 Hz), 132.0 (d, JC-P
=
10.5 Hz), 130.8 (d, JC-P =108.0 Hz), 129.0 (d, JC-P =4.5 Hz),
128.9 (d, JC-P =3.0 Hz), 128.7, 128.0, 127.9 (d, JC-P =30.0 Hz),
126.5 (d, JC-P =118.5 Hz), 126.3 (d, JC-P =10.5 Hz), 124.6 (d,
5a–5d.
The synthetic utility was demonstrated by further
transformations of the obtained phosphorus-containing
3,3’-bisindole derivatives (Scheme 6).[17] Treatment of
3a with BnBr using KOtBu as base afforded the C3-
benzylated product 8 along with little amount of 3-
hydroxyl-2-oxindole 9. The use of NaH as base
improved the yield of 9 in maximum to 74%.
Considering the importance of indole-based phosphine
ligands in some transition metal catalyzed reactions,[18]
We tried the reduction of P=O moiety and fortunately
found 3a could be readily converted to tertiary
phosphine 10 by using the HSiCl3/Et3N system.
J
C-P =21.0 Hz), 122.7, 120.2 (d, JC-P =34.5 Hz), 119.3 (d, JC-P =
12.0 Hz), 112.2, 108.8, 44.2, 44.0; 31P{1H} NMR (243 MHz,
CDCl3): δ=23.2; HRMS (ESI): Exact mass calcd for
C35H27N2O2P [M+H]+: 539.1883, Found: 539.1876.
Acknowledgements
The financial support from the National Natural Science
Foundation of China (21801027), the Sichuan Science and
Technology Program (2018HH0007) and Chengdu University
New Faculty Start-up Funding (2081916045) is highly appre-
ciated.
In summary, we have established a Brønsted acid[19]
catalyzed 1,2-phosphorylation of 3-indolylmethanols
with P(O)-H species, which provided an efficient
protocol for the synthesis of C2-phosphorylated
indoles. Besides widely-used isatin-derived 3-indolyl-
methanols, acyclic α-keto amide, α-keto ester, 1,2-
diphenylketone and diarylketones derived ones could
participate in this reaction, affording the desired
products in moderate to high yields. Mechanistic
studies indicate that this reaction proceeds via a direct
1,2-addition pathway, in which the existence of an
electron-withdrawing group adjacent to the hydroxyl
group of 3-indolylmethanols plays a decisive role. This
protocol not only offers an alternative efficient proto-
col for synthesis of C2-phosphorylated indoles but also
fills the gap of 1,2-addition pathway in the 3-
indolylmethanol-involved reaction modes that still
deserves further exploration.
References
[1] G. W. Gribble, Heterocyclic Scaffolds II: Reactions and
Applications of Indoles, Springer-Verlag, Berlin, Heidel-
berg, 2010.
[2] For some reviews, see: a) F.-E. Chen, J. Huang, Chem.
Rev. 2005, 105, 4671; b) M. Sechi, M. Derudas, R.
Dallocchio, A. Dessi, A. Bacchi, L. Sannia, F. Carta, M.
Palomba, O. Ragab, C. Chan, R. Shoemaker, S. Sei, R.
Dayam, N. Neamati, J. Med. Chem. 2004, 47, 5298;
c) Y.-M. Li, M. Sun, H.-L. Wang, Q.-P. Tian, S.-D. Yang,
Angew. Chem. Int. Ed. 2013, 52, 3972; d) M. Bandini, A.
Eichholzer, Angew. Chem. Int. Ed. 2009, 48, 9608;
e) A. J. Kochanowska-Karamyan, M. T. Hamann, Chem.
Rev. 2010, 110, 4489.
[3] L. Chen, Y.-X. Zou, Org. Biomol. Chem. 2018, 16, 7544.
[4] a) P. Gong, K.-Q. Ye, J.-B. Sun, P. Chen, P.-C. Xue, H.
Yang, R. Lu, RSC Adv. 2015, 5, 94990; b) F. Rataboul,
A. Zapf, R. Jackstell, S. Harkal, T. Riermeier, A.
Monsees, U. Dingerdissen, M. Beller, Chem. Eur. J.
2014, 10, 2983.
Experimental Section
General Procedure for (�)-CSA-catalyzed phosphorylation
of 3-indolylmethanols 1, 4a–4d
Adv. Synth. Catal. 2019, 361, 1–7
5
© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
��
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[5] For selected examples, see: a) H. Wang, X. Li, F. Wu, B. [12] For a recent review, see: a) L. Chen, Y.-X. Zou, X.-Y.
Wan, Synthesis 2012, 44, 941; b) M. Yadav, S. Dara, V.
Saikam, M. Kumar, S. K. Aithagani, S. Paul, R. A.
Vishwakarma, P. P. Singh, Eur. J. Org. Chem. 2015,
2015, 6526; c) W.-B. Sun, J.-F. Xue, G.-Y. Zhang, R.-S.
Zeng, L.-T. An, P.-Z. Zhang, J.-P. Zou, Adv. Synth. Catal.
2016, 358, 1753; d) Z. Zhao, Z. Min, W. Dong, Z. Peng,
D. An, Synth. Commun. 2016, 46, 128; e) R. S. Shaikh, I.
Ghosh, B. König, Chem. Eur. J. 2017, 23, 12120.
[6] M. Min, D. Kang, S. Jung, S. Hong, Adv. Synth. Catal.
2016, 358, 1296.
Liu, X.-J. Gou, Adv. Synth. Catal. 2019, 361, 3490; for
selected examples, see: b) L. Chen, Y.-X. Zou, X.-Y.
Fang, J. Wu, X.-H. Sun, Org. Biomol. Chem. 2018, 16,
7417; c) L. Chen, X.-Y. Fang, Y.-X. Zou, Org. Biomol.
Chem. 2018, 16, 951; d) Y. Nishibayashi, I. Wakiji, M.
Hadai, J. Am. Chem. Soc. 2000, 122, 11019; e) C. Shan,
F. Chen, J. Pan, Y. Gao, P. Xu, Y. Zhao, J. Org. Chem.
2017, 82, 11659; f) X.-R. Song, R. Li, T. Yang, J. Bai, R.
Yang, X. Chen, H. Ding, Q. Xiao, Y.-M. Liang,
Tetrahedron Lett. 2018, 59, 3763; g) Z. M. Hang, J.
Yang, Q. Xu, C. Dong, L.-B. Han, R. Shen, Adv. Synth.
Catal. 2018, 360, 334; h) X. Wo, P. Xie, W. Fu, C. Gao,
Y. Liu, Z. Sun, T.-P. Loh, Chem. Commun. 2018, 54,
11132; i) F. Chen, Y. Xia, R. Lin, Y. Gao, P. Xu, Y. Zhao,
Org. Lett. 2019, 21, 579; j) J.-Y. Du, Y.-H. Ma, R.-Q.
Yuan, N. Xin, S.-Z. Nie, C.-L. Ma, C.-Z. Li, C.-Q. Zhao,
Org. Lett. 2018, 20, 477.
[7] J. Pan, R. Zhao, J. Guo, D. Ma, Y. Xia, Y. Gao, P. Xu, Y.
Zhao, Green Chem. 2019, 21, 792.
[8] For selected reviews, see: a) L. Wang, Y. Chen, J. Xiao,
Asian J. Org. Chem. 2014, 3, 1036; b) H. Wu, Y. P. He,
F. Shi, Synthesis 2015, 47, 1990; c) G.-J. Mei, F. Shi, J.
Org. Chem. 2017, 82, 7695; d) S. Zhu, L. Xu, L. Wang,
J. Xiao, Chin. J. Org. Chem. 2016, 36, 1229.
[9] For selected enantioselective substitutions, see: a) L.-J. [13] CCDC 1899201 for 3a, for details, see the Supporting
Zhou, Y.-C. Zhang, J.-J. Zhao, F. Shi, S.-J. Tu, J. Org. Information.
Chem. 2014, 79, 10390; b) P.-G. Cozzi, F. Benfatti, L. [14] a) H. Huang, H.-J. Pan, Y.-D. Cai, M. Liu, H. Tian, Y.
Zoli, Angew. Chem. Int. Ed. 2009, 48, 1313; c) B. Han,
Y.-C. Xiao, Y. Yao, Y.-C. Chen, Angew. Chem. Int. Ed.
2010, 49, 10189; d) X.-X. Sun, B.-X. Du, H.-H. Zhang,
L. Ji, F. Shi, ChemCatChem 2015, 7, 1211; e) J. Xiao, K.
Zhao, T.-P. Loh , Chem. Asian J. 2011, 6, 2890; f) L. Xu,
H. Chen, J. Liu, L. Zhou, Q. Liu, Y. Lan, J. Xiao, Org.
Shi, Org. Biomol. Chem. 2015, 13, 3566; b) A. A.
Boezio, J. Pytkowicz, A. Coté, A. B. Charette, J. Am.
Chem. Soc. 2003, 125, 14260; c) J.-N. Desrosiers, A. B.
Charette, Angew. Chem. Int. Ed. 2007, 46, 5955;
d) G. M. R. Canlas, S. R. Gilbertson, Chem. Commun.
2014, 50, 5007.
Chem. Front. 2019, 6, 1162; g) L. Song, Q.-X. Guo, X.- [15] a) D.-P. Zhao, D.-X. Yang, Y.-J. Wang, Y. Wang, L.-Q.
C. Li, J. Tian, Y.-G. Peng, Angew. Chem. Int. Ed. 2012,
51, 1899; h) C. Guo, J. Song, J.-Z. Huang, P.-H. Chen,
S.-W. Luo, L.-Z. Gong, Angew. Chem. Int. Ed. 2012, 51,
Wang, L.-J. Mao, R. Wang, Chem. Sci. 2011, 2, 1918;
b) R. G. Pearson, J. Songstad, J. Am. Chem. Soc. 1967,
89, 1827.
1046; i) M. Xiao, D. Ren, L. Xu, S.-S. Li, L. Yu, J. Xiao, [16] We have also checked the reactions of 3-indolylmetha-
Org. Lett. 2017, 19, 5724; j) W. Tan, B.-X. Du, X. Li, X.
Zhu, F. Shi, S.-J. Tu, J. Org. Chem. 2014, 79, 4635; k) J.
Xiao, H. Wen, L. Wang, L. Xu, Z. Hao, C.-L. Shao, C.-Y.
Wang, Green Chem. 2016, 18, 1032; l) Y. Liu, H.-H.
nols 1v and 1w that were derived from 2-methyl and 2-
phenyl substituted indole, respectively, but found no
desired corresponding C2-phosphorylated indoles were
obtained. For details, see supporting information.
Zhang, Y.-C. Zhang, Y. Jiang, F. Shi, S.-J. Tu, Chem. [17] For selected reviews, see: a) A. Steven, L. E. Overman,
Commun. 2014, 50, 12054; m) H. Wen, L. Wang, L. Xu,
Z. Hao, C.-L. Shao, C.-Y. Xiao, Wang, J. Adv. Synth.
Catal. 2015, 357, 4023.
Angew. Chem. Int. Ed. 2007, 46, 5488; b) P. Ruiz-
Sanchis, S. A. Savina, F. Albericio, M. Alvarez, Chem.
Eur. J. 2011, 17, 1388; for recent related examples, see:
c) T.-R. Li, M.-M. Zhang, B.-C. Wang, L.-Q. Lu, W.-J.
Xiao, Org. Lett. 2018, 20, 3237; d) C. Ma, F. Jiang, F.-T.
Sheng, Y. Jiao, G.-J. Mei, F. Shi, Angew. Chem. Int. Ed.
2019, 58, 3014; e) C. Ma, J.-Y. Zhou, Y.-Z. Zhang, Y.
Jiao, G.-J. Mei, F. Shi, Chem. Asian J. 2018, 13, 2549.
[10] a) S. Raucher, A. S.-T. Lui, J. Am. Chem. Soc. 1978,
100, 4902; b) S. Raucher, K.-J. Hwang, J.-E. MacDon-
ald, Tetrahedron Lett. 1979, 20, 3057; c) S. Raucher, J.-
E. MacDonald, R.-F. Lawrence, J. Am. Chem. Soc. 1981,
103, 2419; d) S. Raucher, P. Klein, J. Org. Chem. 1986,
51, 123; e) X. Li, W. Tan, Y.-X. Gong, F. Shi, J. Org. [18] a) C. M. So, C. P. Lau, F. Y. Kwong, Org. Lett. 2007, 9,
Chem. 2015, 80, 1841; f) Y. Liu, R.-Y. Zhu, H.-Z. Li, Y.
Jiang, F. Shi, Synthesis 2015, 47, 1436.
2795; b) D. Saha, R. Ghosh, A. Sarkar, Tetrahedron
2013, 69, 3951; c) C. M. So, Z. Zhou, C. P. Lau, F. Y.
Kwong, Angew. Chem. Int. Ed. 2008, 47, 6402.
[11] For selected reviews on CÀ P bond construction, see:
a) C. S. Demmer, N. Krogsgaard-Larsen, L. Bunch, [19] We also tried using (1R)-(À )-10-camphorsulfonic acid
Chem. Rev. 2011, 111, 7981; b) Q. Xu, L.-B. Han, J.
Organomet. Chem. 2011, 696, 130; c) A. L. Schwan,
Chem. Soc. Rev. 2004, 33, 218; d) H. Zhang, X.-Y.
Zhang, D.-Q. Dong, Z.-L. Wang, RSC Adv. 2015, 5,
52824; e) Y.-M. Li, S.-D. Yang, Synlett 2013, 24, 1739;
f) A. Hosseinian, F. A. S. Nasab, S. Ahmadi, Z. Rahma-
ni, E. Vessally, RSC Adv. 2018, 8, 26383.
and
(R)-(À )-1,1’-binaphthyl-2,2’-diyl-hydrogenphos-
phate as the chiral catalyst for the reaction of 1a and 2a
to examine if the enantioenriched product 3a could be
generated. Unfortunately, 3a was obtained in racemic
form in both cases.
Adv. Synth. Catal. 2019, 361, 1–7
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Synthesis of C2-Phosphorylated Indoles via Metal-Free 1,2-
Phosphorylation of 3-Indolylmethanols with P(O)-H Species
Adv. Synth. Catal. 2019, 361, 1–7
Y.-X. Zou, X.-Y. Liu, J. Zhang, H.-L. Yang, X.-Y. Yang, X.-
L. Liu, Y.-W. Chu, L. Chen*