Atropselective Synthesis of N,C-Bis(diphenylphosphanes) from Bridged 2-Arylindoles Based on Effective Point-to-Axial Asymmetric Inductions after an Unusual Dilithiation ⊥

Article abstract of DOI:10.1021/acs.orglett.9b03896

An asymmetric methanolysis of glutaric anhydride and 6 ensuing steps gave veratrol-annulated dimethylcyclo-heptenone diastereomers with 99% ee; ring closures occurred by Friedel-Crafts acylations of carboxylic acids obtained by stereospecific hydrogenolyses of a pair of diastereomeric δ-lactones. The mentioned cycloheptenones and Ph-NH-NH₂ underwent Fischer indole syntheses providing the tetracyclic indoles cis- and trans-14a, respectively. Double lithiations with BuLi and quenchings with ClPPh₂ furnished the diphosphanes cis- and trans-15 with perfect (P)- and (M)-atropselectivity, respectively.

Full text of DOI:10.1021/acs.orglett.9b03896

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Atropselective Synthesis of N,C-Bis(diphenylphosphanes) from
Bridged 2‑Arylindoles Based on Effective Point-to-Axial Asymmetric
Inductions after an Unusual Dilithiation⊥
̈
̈
Felix Bauerle and Reinhard Bruckner*
Institut fu
̈
r Organische Chemie, Albert-Ludwigs-Universitat, Albertstr. 21, D-79104 Freiburg, Germany
̈
S
* Supporting Information
ABSTRACT: An asymmetric methanolysis of glutaric anhydride and 6 ensuing steps gave veratrol-annulated dimethylcyclo-
heptenone diastereomers with 99% ee; ring closures occurred by Friedel−Crafts acylations of carboxylic acids obtained by
stereospecific hydrogenolyses of a pair of diastereomeric δ-lactones. The mentioned cycloheptenones and Ph−NH−NH2
underwent Fischer indole syntheses providing the tetracyclic indoles cis- and trans-14a, respectively. Double lithiations with
BuLi and quenchings with ClPPh2 furnished the diphosphanes cis- and trans-15 with perfect (P)- and (M)-atropselectivity,
respectively.
nantiomerically pure diphosphanes are abundantly used
1
Eligands in asymmetric catalysis. An important subclass
thereof contains a diisocyclic C2-symmetric 1,1′-biaryl-2,2′-
bis(diphosphane) scaffold. The most famous diphenylphos-
phane of this design is BINAP.2 Many variations thereof are
known, including H8-BINAP,3 SEGPHOS,4 DIFLUOR-
PHOS,5 SUNPHOS,6 SYNPHOS,7 SOLPHOS,8 a nameless
aza analog thereof,9 and many others.1 Related diphosphane
designs are BIPHEMP,10 MeO-BIPHEP,11 CnTunaPhos =
Figure 1. C2-symmetric 3,3′-biindolyl-2,2′-bis(diphosphane) 1,16 2,2′-
TUNEPHOS,12 Bu-PQ-PHOSPHOS,13 Pent-PQ-PHOS-
biindolyl-1,1′-bis(diphosphane) 2,17 and 2,2′-biindolyl-3,3′-bis-
PHOS,14 Hex-PQ-PHOSPHOS,14 and many more.1 Almost
all diphosphanes of this kind have been synthesized atrop-
unselectively: by resolving the racemic phosphane, the
corresponding racemic bis(phosphane oxide), or a racemic
precursor. The only atropselective syntheses in this series used
point-to-axial asymmetric inductions which allowed Ullmann
couplings (inter alia) to afford the bis(phosphane oxide)
precursors of one diphosphane with ds = 78:228 and of three
other diphosphanes with de ≥ 98%.13,14
Diheterocyclic C2-symmetric 1,1′-biaryl-2,2′-bis-
(diphosphanes) have been reported as well.15 Figure 1
illustrates them by the biindolyldiphosphanes 1−4.16−19
Compounds 1−3b16−18 and all respective diphosphanes
based on other heterocycles20 stem from resolving racemic
mixtures, wherein the biaryl axis had been established without
atropcontrol. The only atropselective diphosphane syntheses in
this series exploited point-to-axial asymmetric inductions in
two dibrominations of a 2,2′-biindolyl (ds = 95:5 and 5:95).19
(diphosphanes) 3a,b,18 and 4.19
Refunctionalizations afforded the diphosphanes 4 [= (R,R,P)-
4] and dia-4 [= (R,R,M)-4] atropisomerically pure.19
Monoheterocyclic and therefore only C1-symmetric
biarylbis(diphenylphosphanes) exist, too. Those with an
arylindole scaffold (5−9,21−23 Figure 2) can be regarded as
hybrids of the earlier mentioned diisocyclic C2-symmetric 1,1′-
biaryl-2,2′-bis(diphosphane) scaffolds and the diphosphane
motifs from Figure 1. None of them has been obtained
atropisomerically pure yet. In contrast, the present study
reveals perfectly atropselective syntheses of the arylindole
diphosphanes cis-15, which is P-configured, and trans-15,
which is M-configured (formulas: Figure 4).
Received: October 31, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b03896
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
our concept, we synthesized their representatives cis- and trans-
14a34 and derived the arylindolediphosphanes cis- and trans-15
therefrom (formulas: Figure 4).
Figure 2. Arylindole-based diphosphanes known to date.
Our approach was inspired by a 60 year old observation:24
The UV absorption of the cycloheptadieno-phenylindole 10
(Figure 3) exhibits a hypsochromic shift relative to the
Figure 4. C1-symmetric biarylbis(diphosphanes) cis-15 and trans-15,
their precursors cis-14a and trans-14a (cf. Figure 3), and their
conceived origin from the enantiomerically pure δ-ketoester 18.
Figure 3. Cycloheptadieno-2-arylindoles: scaffolds with temporary, if
not permanent twists.
analogous cyclohexadieno-phenylindole.24 This was attributed
to a decreased conjugation across the indole-phenyl bond due
to “the polymethylene chain acting as a lever which turns the
benzene moiety out of the indole plane”.24 The resulting twist
about the phenyl-indole bond causes the formation of an
(equilibrating) 50:50 mixture of an (M)- and a (P)-
atropisomer.25 We wanted to design cycloheptadieno-phenyl-
indoles which would twist unidirectionally (with or without
equilibrating with each other) and thereby result as single
atropisomers in a conceptually novel manner.
Our retrosynthetic analyses of the cyloheptadieno-arylin-
doles cis- and trans-14a proceeded via the equally configured
cylohepteno-veratroles cis- and trans-17, respectively, to the
veratrol-containing δ-ketoester 18 (Figure 4). Its aliphatic
moiety should originate from an unsymmetric derivative 16 of
3-methylglutaric acid. Type-16 compounds can be obtained by
desymmetrizing 3-methylglutaric anhydride (19) by an
asymmetric methanolysis.35 We started synthesizing com-
pounds cis- and trans-14a using Bolm’s variant36 of such a
reaction37 (Scheme 1). Methanolysis of 19 in chlorobenzene
rather than in CCl436,38 provided 97% of the glutaric half-ester
16a with 70% ee;39 three low-temperature recrystallizations40a
of the salt(s)40 formed with 1.0 equiv of (−)-cinchonidine
increased the ee39 of regenerated 16a to 99%. This compound
was converted into the acid chloride 16b. Without purification,
a CH2Cl2 solution acylated veratrol (20) at room temp after
the addition of 1.0 equiv of either AlCl3 or Me2AlCl. To our
surprise, the resulting δ-ketoester 18 was racemic.41,42 We
surmise that racemization occurred by the mechanism
suggested in Scheme 2.
We proceeded to the (R)-configured δ-ketoester 18 rather
than to rac-18 after activating the glutaric half-ester 16a as the
S-ethyl thioester 16c, which we isolated in 70% yield, or as the
mixed anhydride 16d (accessed with MeO2C−O−CO2Me43
rather than with MeO2C−Cl), which we carried on without
purification (Scheme 1). The thioester 16c and an excess of
veratrylzinc halide 21a (prepared from 4-iodoveratrol by
succcessive I → Li and Li → ZnCl exchanges) coupled in a
Fukuyama ketone synthesis.44 It delivered over 60% of the δ-
ketoester 18. However, this compound was hard to separate
from considerable amounts of accompanying 3,3′,4,4′-
tetramethoxybiphenyl by flash chromatography on silica
gel.45 Coupling the mixed anhydride 16d with the veratrolbor-
onic acid 21b [prepared from 4-bromoveratrol as described;46
The atropisomerization of a few derivatives of the
unsubstituted cycloheptadieno-phenylindole 1026 and some
related biaryls was studied by 1H NMR spectroscopy:
Compound 1327 did not atropisomerize, but compounds
1128 and 1227 did. Biphenylrather than 2-phenylindole
c o n t a i n i n g
a
C H 2 − C H 2 − C H 2 b r i d g e
(ΔG‡
= 12.5 kcal/mol29)
atropisomerization in the 1H NMR spectrometer
and their CH2−C(CO2Et)2−CH2- or CH2−O−CH2-contain-
ing analogs atropisomerize with similar rates.30 A biphenyl with
a meso-configured C(Me)H−NH−C(Me)H bridge atropiso-
merizes more slowly (ΔG‡ = 13.6 kcal/mol31) and a biphenyl
with a O−CH2−O bridge much faster (ΔG‡ ≈ 1 kcal/mol32).
Related biphenyls contain the chiral bridges C(Me)H−NH−
C(Me)H31 or CH2−NH−C(Me)H33 and are single atrop-
isomers. Their stereocenter(s) differentiate(s) the stabilities of
the respective (diastereomorphic!) atropisomers so much that
the more stable atropisomer does not cross the atropisome-
rization barrierno matter how low it might bebecause there
is no driving force.
The preceding insights and our objective of modifying the
(P)- and (M)-twisted scaffold 10 to exclusively (P)- or
exclusively (M)-twisted derivatives let us screen the
atropisomerical preferences of several type-14 and type-dia-
14 cyloheptadieno-arylindoles (formulas: Figure 3). Proving
B
DOI: 10.1021/acs.orglett.9b03896
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
a
Scheme 1. Synthesis of δ-Ketoester 18
Scheme 3. Synthesis of the Cycloheptadieno(arylindolyls)
cis- and trans-14
a
a
Reaction conditions: (a) MeOH (3.0 equiv), (−)-quinine (1.1
equiv), chlorobenzene/toluene (1:1), −55 °C, 72 h; 97%, 70% ee; (b)
(−)-cinchonidine (1.0 equiv), acetone/H2O, 40 °C → 4 °C, 24 h; aq.
HCl (1 M); 20%, 99% ee; (c) (COCl)2 (1.1 equiv), DMF (cat.),
CH2Cl2, room temp, 3 h; (d) AlCl3 (1.0 equiv), 20 (1.0 equiv),
CH2Cl2, room temp, 20 h; 97% over the 2 steps; (e) same as (d) but
Me2AlCl (1.0 equiv); 89% over the 2 steps; (f) DCC (1.0 equiv),
EtSH (1.0 equiv), DMAP (20 mol %), CH2Cl2, room temp, 18 h;
70%; (g) MeO2C−O−CO2Me (3.0 equiv), 21b (1.2 equiv),
Pd(OAc)2 (3.0 mol %), P(p-anisyl)3 (7.0 mol %), H2O (17 mol
%), THF, 80 °C, 16 h; 79%; (h) 21a (3.0 equiv), PdCl2(PPh3)2 (5.0
mol %), THF, room temp, 16 h; 60% over the 2 steps.
Scheme 2. Mechanism of the Enantiomerization 16b → ent-
16b Which Causes the Racemization of the Acid Chloride
16b under both Friedel−Crafts Acylation Conditions of
Scheme 1
a
Reaction conditions: (a) MeMgCl (1.5 equiv), THF, −78 °C →
room temp, 18 h; 37% 29,47a 25% dia-29,47b 20% de; (b) H2
(balloon), Pd/C (10 wt-%, 15 mol %), EtOH, room temp, 19 h;
90% 30 or 92% dia-30; (c) Polyphosphoric acid (10 times the mass of
30 or dia-30), sulfolane, 100 °C, 1 h; 90% cis-1747c or 88% trans-17;
(d) PhNHNH2 (1.0 equiv), HCl (concd, 4.0 equiv), EtOH, reflux, 24
h; 72% cis-14 or 68% trans-17.
bonds akin to our examples 29 → 30 and dia-29 → dia-30 and
proceeding with inversions of configurations, too, were first
investigated by Mitsui et al.48 One such hydrogenolysis of a
tolyl-substituted δ-lactone was accomplished by Campagne et
al.49 during our own studies.
yield: 56% (60%46)] was a better synthesis43a of the desired δ-
ketoester 18 because no difficult to separate 3,3′,4,4′-
tetramethoxybiphenyl interfered.
Our cycloheptadieno-arylindole syntheses continued by
adding MeMgCl to the carbonyl group of the δ-ketoester 18
(Scheme 3). Quenching the reaction mixture with satd. aq.
NaHCO3, extractive workup, and purification by flash
chromatography on silica gel45 furnished no δ-hydroxyesters
but the derived valerolactones 2947a and dia-2947b with ds =
60:40. Next, the benzylic C−O bonds of lactones 29 and dia-
29 were hydrogenolyzed in EtOH catalyzed by 15 mol % Pd/
C. Under this proviso, both hydrogenolyses exhibited ≥95%
inversion of configuration. This rendered the carboxylic acids
30 (whose follow-up product cis-17 was X-rayed,47c revealing
the steric course of the preceding hydrogenolysis) and dia-30,
respectively. Less Pd/C, other catalysts [Pd-black, Pd(OH)2],
or other solvents (MeOH, AcOEt, and 2-Me-THF) gave
inferior selectivities. Hydrogenolyses of tertiary Cbenzylic−O
At 100 °C the carboxylic acids 30 and dia-30 underwent
Friedel−Crafts cyclizations in polyphosphoric acid50 which we
diluted with sulfolane51 to improve miscibilities and thereby
increase yields (Scheme 3). This led to the benzosuberone cis-
1747c in 90% yield rather than only in 53% yield and to the
benzosuberone trans-17 in 88% yield. Cis-17 crystallized from
n-hexane with dr = 100:0 while trans-17 remained an oil with
dr = 95:5. The last steps of Scheme 3 are Fischer indole
syntheses combining the Friedel−Crafts products cis-17 or
trans-17 with phenylhydrazine in hot ethanolic HCl.52 A 72%
yield of the bridged arylindole cis-14 resulted from cis-17, and a
68% yield of trans-14 resulted from trans-17. Cis-14 was
diastereopure immediately, whereas trans-14 had to be
crystallized to become diastereopure.
C
DOI: 10.1021/acs.orglett.9b03896
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Organic Letters
Letter
The H−N−C2−C1′−C2′−H motifs of the arylindoles cis-
were not only atropselective but additionally atropdivergent.
These findings underline the viability of a concept first laid out
in the discussion of Figure 3.
and trans-14 gave Li−N−C2−C1′−C2′−Li motifs upon
exposure to 2 equiv of nBuLi provided that TMEDA was
present (Scheme 4, not depicted). Treatment with ClPPh2
ASSOCIATED CONTENT
* Supporting Information
■
S
Scheme 4. N-Directed Lithiation/Phosphorylation of the
Cycloheptadieno(indolylaryls) cis- and trans-14; Lithiation
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.9b03896.
a
Analogies and Differences
Experimental procedures, characterization data, NMR
spectra, and details concerning the X-ray analyses.
(PDF)
Accession Codes
CCDC 1533413, 1533414, 1549686, 1561798, and 1578270
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge via www.ccdc.ca-
m.ac.uk/data_request/cif, or by emailing data_request@ccdc.
cam.ac.uk, or by contacting The Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; fax:
+44 1223 336033.
AUTHOR INFORMATION
Corresponding Author
■
*E-mail: reinhard.brueckner@organik.chemie.uni-freiburg.de.
ORCID
Reinhard Bruckner: 0000-0002-9028-8436
̈
Notes
a
Reaction conditions: (a) nBuLi (2.5 equiv), TMEDA (2.5 equiv),
The authors declare no competing financial interest.
Et2O, room temp, 3 h; ClPPh2 (10 equiv), −78 °C → room temp, 18
h; 72%;47d (b) Same as (a); 63%;47e (c) Reference 53; LiTMP (5.0
equiv), THF, −10 °C, 1 h; HCO2Et (1.0 equiv), TMSCl (10.0 equiv),
−78 °C → room temp; 75%; (d) Same as (a) but using sBuLi instead
of nBuLi; 40%.
ACKNOWLEDGMENTS
We are grateful to Ina Klaproth for skilled technical assistance
and to Dr. Daniel Kratzert and Bouhmadi Benkmil (Institut fu
■
̈
r
Anorganische und Analytische Chemie) for the X-ray structure
analyses.
established the Ph2P−N−C2−C1′−C2′−PPh2 motifs of the
diphosphane targets cis- and trans-15. Purification by flash
chromatography on silica gel45 rendered cis-15 in 72% yield
and trans-15 in 63% yield.
DEDICATION
■
⊥Dedicated to Professor Rolf Huisgen at the occasion of his
99th birthday.
The double C- and N-lithiation employed in the last step of
our routes to the diphosphanes cis- and trans-15 was
unprecedented. The closest-related dilithiation of that kind
was the transformation 31 → 3353 (Scheme 4; the NH group
of 31 belongs to a vinylogous amide and thus should be more
acidic than the NH group of the indoles cis- and trans-14). The
feasibility of lithiating a 2-arylindole twice does not require the
support of a MeO group: 3-Methyl-2-phenylindole (32) was
both C- and N-lithiated with sBuLi (though not with nBuLi);
this allowed progression to the previously described54
diphosphane 8 in 40% yield.55
In the solid state, the N−C2−C1′−C2′ motifs of our
diphosphanes are twisted in opposite senses. These twists
allow the following dihedral angle quantifications: +62.8° in
cis-1547d and −67.9° in trans-15.47e The different signs of these
angles are due to the biaryl axis being (P)-configured in
diphosphane cis-15 yet (M)-configured in trans-15. This
contrast arises in response to the changing configurations of
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DOI: 10.1021/acs.orglett.9b03896
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
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(17) Benincori, T.; Brenna, E.; Sannicolo, F.; Trimarco, L.;
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(18) Benincori, T.; Piccolo, O.; Rizzo, S.; Sannicolo, F. J. Org. Chem.
́
́
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Pedrosa, R. J. Org. Chem. 2010, 75, 5417−5420.
(40) (a) Low-temperature recrystallization: Lehr, K.; Furstner, A.
̈
́
Tetrahedron 2012, 68, 7695−7700. (b) Original recrystallization:
́
́
2000, 65, 8340−8347.
Poppe, L.; Novak, L.; Kolonits, P.; Bata, A.; Szantay, C. Tetrahedron
1988, 44, 1477−1487.
(19) Baumann, T.; Bruckner, R. Angew. Chem. 2019, 131, 4762−
̈
4768; Angew. Chem., Int. Ed. 2019, 58, 4714−4719.
(41) The ee of the δ-ketoester 18 was determined by HPLC (details:
Supporting Information).
̀
(20) (a) Benincori, T.; Brenna, E.; Sannicolo, F.; Trimarco, L.;
Antognazza, P.; Cesarotti, E.; Demartin, F.; Pilati, T. J. Org. Chem.
(42) (a) The conditions of step (e) of Scheme 1 allowed 5-chloro-
2-hexyl-1-methylindole to be acylated with the acid chloride 16b (ee
not reported) within 1 h which gave 90% of a δ-ketoester of 80% ee:
Patel, P.; Reddy, C. N.; Gore, V.; Chourey, S.; Ye, Q.; Quedraogo, Y.
P.; Gravely, S.; Pawell, W. S.; Rokack, J. ACS Med. Chem. Lett. 2014,
5, 815−819. The indole is more nucleophilic than veratrol (20) and
thus leaves less or no time for the acid chloride 16b to racemize.
(43) Method: (a) Gooßen, L. J.; Ghosh, K. Angew. Chem. 2001, 113,
3566−3568; Angew. Chem., Int. Ed. 2001, 40, 3458−3460.
(b) Gooßen, L. G.; Winkel, L.; Dohring, A.; Ghosh, K.; Paetzold, J.
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(44) Method: Tokuyama, H.; Yokoshima, S.; Yamashita, T.;
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(45) Still, W. C.; Kahn, M.; Mitra, A. J. Org. Chem. 1978, 43, 2923−
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́
1996, 61, 6244−6251. (b) Benincori, T.; Brenna, E.; Sannicolo, F.;
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O.; Sannicolo, F. J. Org. Chem. 2000, 65, 2043−2047. (d) Andersen,
N. G.; Parvez, M.; McDonald, R.; Keay, B. A. Org. Lett. 2000, 2,
2817−2820. (e) Pai, C.-C.; Lin, C.-W.; Lin, C.-C.; Chen, C.-C.; Chan,
A. S. C. J. Am. Chem. Soc. 2000, 122, 11513−11514.
(21) Artemova, N. V.; Chevykalova, Ma. N.; Luzikov, Y. N.;
Nifant’ev, I. E.; Nifant’ev, E. E. Tetrahedron 2004, 60, 10365−10370.
(22) Kuang, F.; Su, Q.; Zhou, Y.; Yuan, A. Faming Zhuanli Shenqing
2017, CN 107445989 A 20171208.
̈
̀
(23) Sannicolo, F.; Benincori, T.; Rizzo, S.; Gladiali, S.; Pulacchini,
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(24) Huisgen, R.; Ugi, I. Justus Liebigs Ann. Chem. 1957, 610, 57−66.
(25) In this letter, “atropisomer”, “to atropisomerize”, and
“atropisomerization” refer to biaryls exchanging an (M)-conformation
about their biaryl axis for a (P)-conformation or undergoing the
reverse processes, by which “(P)-configured biaryl atropisomers”
render “(M)-configured biaryl atropisomers”.
(46) Zhang, Q.-Q.; Xie, J. H.; Yang, X.-H.; Xie, J.-B.; Zhou, Q.-L.
Org. Lett. 2012, 14, 6158−6161.
(47) (a) Racemic lactone 29 formed crystals whose structure was
elucidated by X-ray analysis; the corresponding data are contained in
CCDC 1578270. (b) Racemic lactone dia-29 formed crystals whose
structure was elucidated by X-ray analysis; the corresponding data are
contained in CCDC 1533413. (c) Racemic benzosuberone cis-17
(obtained by the Friedel−Crafts acylation of the hydrogenolysis
product dia-29) formed crystals whose structure was determined by
1
(26) 100 H NMR spectrum of compound 10: Hong, B.-C.; Jiang,
Y.-F.; Chang, Y.-L.; Lee, S.-J. J. Chin. Chem. Soc. 2006, 53, 647−662.
(27) 100 MHz 1H NMR spectra of compounds 12 and 13: Fujimori,
K.; Yamane, K. Bull. Chem. Soc. Jpn. 1978, 51, 3579−3581.
E
DOI: 10.1021/acs.orglett.9b03896
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
X-ray crystallography; the corresponding data are contained in CCDC
1533414. (d) Racemic diphosphane cis-15 formed crystals whose
structure was elucidated by X-ray analysis; the corresponding data are
contained in CCDC 1549686. (e) Racemic diphosphane trans-15
formed crystals whose structure was elucidated by X-ray analysis; the
corresponding data are contained in CCDC 1561798.
(48) (a) Mitsui, S.; Iijima, K.; Masuko, T. Nippon Kagaku Zasshi
1963, 84, 833−838. (b) Mitsui, S.; Imaizumi, S.; Takamura, I.;
Takamura, M. Nippon Kagaku Zasshi 1963, 84, 838−841. (c) Mitsui,
S.; Iijima, K.; Masuko, T. J. Chem. Soc. Japan, Pure Chem. Sect. (Nippon
Kagaku Zasshi) 1963, 84, 842−845. (d) Konno, K.; Mitsui, S. Nippon
Kagaku Zasshi 1964, 85, 497−500. (e) Mitsui, S.; Iijima, K. J. Chem.
Soc. Japan, Pure Chem. Sect. (Nippon Kagaku Zasshi) 1964, 86, 682−
686. (f) Mitsui, S.; Kudo, Y.; Kobayashi, M. Tetrahedron 1969, 25,
1921−1927. (g) Mechanistic studies: Garbisch, E. W., Jr.; Schreader,
L.; Frankel, J. J. J. Am. Chem. Soc. 1967, 89, 4233−4235.
(49) Spielmann, K.; de Figueiredo, R. M.; Campagne, J.-M. J. Org.
Chem. 2017, 82, 4737−4743.
(50) Method: Uhlig, F. Angew. Chem. 1954, 66, 435−436.
(51) Method: Nelson, P. H.; Untsch, K. G. U.S. Patent 4038299A
1977.
(52) Reaction conditions: Dufour, F.; Kirsch, G. Synlett 2006, 2006,
1021−1022.
(53) Scopton, A.; Kelly, T. R. J. J. Org. Chem. 2005, 70, 10004−
10012.
(54) Reference 23 prepared the same diphosphane 8 via the identical
dilithio intermediate but gained the latter by converting a N−H to a
N−Li bond (monolithiation) and a C−Br to a C−Li bond (Li/Br
exchange).
(55) 2-Phenylindole underwent such a dilithiation, too. Quenching
with Ph2PCl delivered a complex mixture but quenching with
Me3SiCl led to 3-(trimethylsilyl)-2-[2-(trimethylsilyl)phenyl]indole in
50% yield.
F
DOI: 10.1021/acs.orglett.9b03896
Org. Lett. XXXX, XXX, XXX−XXX