A Simple Synthesis of 3,3-Diphenylcyclopropene

Full text of DOI:10.1080/00304948.2020.1794223

Organic Preparations and Procedures International
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A Simple Synthesis of 3,3-Diphenylcyclopropene
Alexey V. Nizovtsev
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ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
https://doi.org/10.1080/00304948.2020.1794223
OPPI BRIEF
A Simple Synthesis of 3,3-Diphenylcyclopropene
Alexey V. Nizovtsev
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences,
Moscow, Russia
ARTICLE HISTORY Received 29 April 2020; Accepted 29 May 2020
In organometallic chemistry, 3,3-diphenylcyclopropene 1 is a very attractive compound
1
for the preparation of metal vinyl carbene complexes 2 (Scheme 1). Perhaps the most
notable application was in the synthesis of the first-generation olefin metathesis catalysts
2
,3
4–6
6
7
8,9
promoted by Grubbs. In addition, vinyl carbene complexes of W,
Mo, Ti, Ru,
1
0
11
12
Re, Co and Ta have been prepared using 1. Several of its reactions promoted by
Zn or Rh compounds are also supposed to proceed with participation of carbene
1
3
14
complexes 2, and the formation of these species is proposed in certain reactions of 1 on
1
5
bulk gold metal surfaces. The compound has been used as a highly versatile substrate
1
6–18
for further structural elaboration.
Unfortunately, wider application of this com-
pound is restricted due to the lack of its rapid and convenient synthesis.
The traditional method of preparation of 1 takes place in three steps from 1,1-diphe-
nylethylene 3 (Scheme 2): 1) synthesis of cyclopropane 4; 2) partial reduction of the
CBr moiety; and 3) 1,2-elimination of HBr. This synthetic scheme has been used by a
2
1
4,18,19
number of researchers.
Methods of gem-dibromocyclopropane synthesis are well known and a convenient
20
18,19
preparation of cyclopropane 4 has been described,
but most of the drawbacks occur
during the further two steps. Several publications have reported the partial reduction of
1
2
dibromide 4 using different reagents including nBu SnH, silanes under blue LED
3
2
1
18,19,22
irradiation with Ir catalyst,
Grignards in the presence of Ti(OiPr)4
Fe(acac)3. Further elimination of HBr from 5 has been achieved by treatment with
tBuOK in dry DMSO and led to the desired product 1 with yields up to 96%.
or
2
3
12,18,19
Despite the high yields, the application of toxic compounds and the requirement for
column chromatography on silica gel at each step have limited these procedures.
We have chosen the same strategy for the preparation of cyclopropene 1 (Scheme 2)
but with some differences in synthetic protocols, which we now report. Thus, dibromide
4
was successfully reduced via the generation of an a-bromocyclopropylmagnesium
2
4
reagent followed by work-up with methanol at low temperature. In addition, mono-
bromide 5 was obtained by traditional reduction of 4 with EtMgBr promoted by Ti
2
5,26
compounds
but ether was replaced with THF and Ti(OiPr) with TiCl (THF) . This
4 4 2
25,26
resulted in the absence of any polar products
in the reaction mixture after aqueous
workup, greatly simplifying the product purification. Both methods provided 5 with
yields of 93-94% and purity greater than 99%. If necessary, the product could be further
CONTACT Alexey V. Nizovtsev
alexey.nizovtsev@gmail.com
Shemyakin-Ovchinnikov Institute of Bioorganic
Chemistry, Russian Academy of Sciences, Moscow, Russia.
ß 2020 Taylor & Francis Group, LLC

2
A. V. NIZOVTSEV
Ph
Ph
MLn
+
MLn
1
2
Scheme 1. Synthesis of metal vinylcarbene complexes from 3,3-diphenylcyclopropene 1.
a)
b) or c)
d)
Br
3
4
5
1
Br
Br
ꢀ
Scheme 2. Reagents and conditions: a) CHBr , tBuOK, hexane, ꢁ20 C, 1 h, 67%; b) 1. EtMgBr, THF,
3
ꢀ
ꢀ
ꢁ
65 C, 40 min; 2. MeOH, ꢁ70 C, 93%; c) EtMgBr, TiCl (THF) (2.5 mol.%), THF, RT, 10 min, 94%;
4
2
d) tBuOK, THF, RT, 19 h, 99%.
purified by crystallization from hexane (see Experimental section). Cyclopropene 1 was
prepared in 99% yield by elimination of HBr from 5 with tBuOK using dry THF instead
27
of DMSO. We have demonstrated that, in contrast to the reported procedure, the reac-
tion proceeds successfully without 18-crown-6. This is important because 18-crown-6 is
known to catalyze the addition of tert-butoxide anion to a double bond of cyclopro-
2
8
penes. Compound 1 thereby obtained did not require additional purification.
To conclude, we demonstrated that cyclopropene 1 can be easily obtained without
the use of toxic compounds and without the requirement of column chromatography.
We hope this method will stimulate further research in the field of metal vinyl carbene
complexes 2.
Experimental section
All reagents were obtained from commercial suppliers and were used without further
purification unless stated. Organic solutions were dried over anhydrous Na SO or
2
4
MgSO , filtered and, unless stated, were evaporated at 8 mbar. Yields quoted are for the
4
purified compounds. All compounds were homogeneous by TLC. TLC was performed
using ALUGRAM SIL G/UV254 (MACHEREY-NAGEL) with hexane as the eluting
solvent. Compounds were visualized either by examination under an ultraviolet source
or by contact with phosphomolybdic acid hydrate (2% solution in ethanol) followed by
ꢀ
heating to 200 C. Melting points are uncorrected. NMR spectra were recorded at 303K
on a Bruker Avance 400 or a Bruker AC-250 spectrometer operating at 400 MHz and
250 MHz for protons and 100 MHz and 62.9 MHz for carbon and in the latter case were
broad-band decoupled. Residual solvent signals were used as internal standards. IR spec-
tra were recorded on a Perkin Elmer 1600 FTIR apparatus. Ethylmagnesium bromide
was synthesized immediately prior use and titrated using the following procedure: the
aliquot of Grignard reagent (1.0 ml) was poured into deionized water (5 ml) and 0.1 M
HCl (20 ml) was added. The resulting solution was titrated with 0.1 M NaOH in the
presence of methyl orange.

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
3
1,1-Diphenylethylene (3)
A three-neck round bottom flask (500 ml) equipped with a reflux condenser, a thermometer,
a dry argon inlet, a dropping funnel and a magnetic stir bar was charged with magnesium
turnings (10.453 g, 430 mmol) and dry ether (200 ml) under argon. A solution of phenyl
bromide (69.09 g, 46.4 ml, 440 mmol) in dry ether (50 ml) was added in portions over 1.5 h
in such manner that after the initiation step the reaction mixture was gently boiling. After
ꢀ
complete addition the mixture was refluxed for 1.5 h and cooled to þ8 C. A solution of
acetophenone (48.06 g, 46.7 ml, 400 mmol) in dry ether (50 ml) was added to the prepared
ꢀ
Grignard reagent over 45 min keeping the temperature below þ17 C. The resulting vis-
ꢀ
cous suspension was refluxed for 30 min, cooled to þ7 C and a mixture of concentrated
ꢀ
HCl (90 ml) and water (60 ml) was carefully added keeping the temperature below þ25 C.
The organic layer was separated and the water layer was extracted with benzene (3x50 ml).
The organic layers were combined, concentrated in vacuo and 50% phosphoric acid (90 ml)
ꢀ
was added. The resulting mixture was heated at 120 C (external bath) for 1 h, cooled to
room temperature, the organic layer was separated and the aqueous layer was extracted
with benzene (3x30 ml). The combined organic layers were washed with saturated
NaHCO , saturated NH Cl, brine and dried over MgSO . After filtration, the solvent was
3
4
4
distilled off at atmospheric pressure. Vacuum distillation of the residue afforded 1,1-diphe-
ꢀ
nylethylene 3 (60.84 g, 338 mmol, 84%) as a colorless oil with bp 106-110 C/2 mbar
2
9
ꢀ
ꢁ1
(
1
(
lit bp 117-118 C/3.3mbar). IR (KBr, neat, cm ): 3079, 3056, 3028, 1610, 1601, 1574,
494, 1443, 1328, 1065, 1027, 899, 773, 698. H NMR (CDCl ): d 7.45-7.38 (m, 10H), 5.55
1
3
1
3
s, 2H). C NMR (CDCl ): d 150.1, 141.6, 128.3, 128.2, 127.8, 114.1.
3
1
,1-Dibromo-2,2-diphenylcyclopropane (4)
Bromoform (27.8 g, 9.6 ml, 110 mmol, 1.1 mol eq) was added to a mixture of 1,1-diphe-
nylethylene 3 (18.025 g, 100 mmol) and tBuOK (16.833 g, 150 mmol, 1.5 mol.eq.) in
ꢀ
ꢀ
hexane (300 ml) at -20 C over 15 min keeping the temperature near -25 C. The result-
ꢀ
ꢀ
ing suspension was stirred at ꢁ25 to ꢁ20 C for 1 h and then at 0 C for another 1 h.
Water (50 ml) was added and the organic solvent was evaporated in vacuo. The residue
was dissolved in CH Cl (200 ml), the organic layer was separated and the water layer
2
2
was extracted with CH Cl (3x30 ml). The combined organic layers were washed with
2
2
5
% HCl (3x30 ml), dried over MgSO and, after filtration, evaporated in vacuo. The
4
product was isolated by recrystallization from hot toluene (1 ml of solvent per 1 g of the
mixture). 1,1-Dibromo-2,2-diphenylcyclopropane 4 (19.86 g) was obtained as colorless
ꢀ
30
ꢀ
crystals with mp 157-159 C (lit mp 154-156 C). The mother liquor was evaporated
in vacuo and twice recrystallized from hot toluene to give further crops of the product.
1
The overall yield of 4 was 23.51 g (67 mmol, 67%). H NMR (CDCl ): d 7.46-7.41
3
13
(
m, 4H), 7.27-7.20 (m, 4H), 7.18-7.12 (m, 2H), 2.40 (s, 2H). C NMR (CDCl ): d
3
142.0, 129.4, 128.6, 127.5, 45.3, 34.7, 34.1.
Ethylmagnesium bromide in THF
A two-neck round bottom flask (250 ml) was charged with magnesium turnings
(2.917 g, 120 mmol, 1.2 mol eq) and dry THF (86 ml) under an inert atmosphere of

4
A. V. NIZOVTSEV
nitrogen. A solution of ethylbromide (10.9 g, 7.5 ml, 100 mmol) in dry THF (14 ml) was
added in portions in such a manner that after the initiation step the reaction mixture
was gently boiling. The overall time of addition was 30 min. After the addition the reac-
tion was stirred for an additional one hour at room temperature and titrated. The con-
centration of EtMgBr was 1.0 M.
Tetrachlorobis(tetrahydrofuran)titanium (IV), TiCl (THF)
4
2
Titanium tetrachloride (3.794 g, 2.2 ml, 20 mmol) was added slowly to dry THF (40 ml)
ꢀ
at ꢁ65 C with stirring by a magnetic stir bar under an inert atmosphere of argon
ꢀ
maintaining the temperature of the reaction mixture below ꢁ40 C. A strong exother-
mic effect was observed. The color turned to yellow and a large amount of precipitate
was formed. After the addition the mixture was stirred at room temperature for an add-
3
1–33
itional hour and evaporated in vacuo to give TiCl (THF)
(6.575 g, 19.7 mmol,
4
2
ꢀ
31
ꢀ
1
9
8%) as yellow crystals with mp 111-114 C (dec) (lit mp 126-128 C). H NMR
1
3
(
CDCl ): d 4.6-4.3 (m, 4H), 2.2-1.9 (m, 4H). C NMR (CDCl ): d 75.0, 25.6.
3
3
1
,1-Diphenyl-2-bromocyclopropane (5)
Method A: EtMgBr (48 ml, 1.0 M in THF, 48 mmol, 4 mol eq) was added to a solution
of 1,1-dibromo-2,2-diphenylcyclopropane 4 (4.225 g, 12 mmol) in dry THF (24 ml)
ꢀ
under an inert atmosphere of nitrogen at ꢁ70 C over 20 min. The temperature of the
ꢀ
reaction mixture was maintained during the addition below ꢁ65 C. The reaction mix-
ꢀ
ꢀ
ture was stirred at ꢁ67 to ꢁ61 C for another 30 minutes and cooled to -80 C.
ꢀ
Methanol (4 ml) was added carefully keeping the temperature below ꢁ70 C. A strong
exothermic effect was observed. The reaction mixture was warmed to room tempera-
ture, water (7 ml) was added and the resulting suspension was stirred for an hour. The
clear solution of the product was decanted, the remained solid triturated with ether
(2x15 ml) and the ether solutions were combined with the THF solution. The solid was
dissolved in a small amount of 5 M HCl, extracted with CH Cl (2x10 ml) and all com-
2
2
bined organic layers were dried over Na SO . After filtration, the solvent was evapo-
2
4
rated in vacuo, the residual viscous yellowish oil was dissolved in warm hexane (50 ml),
filtered and the solvent was evaporated in vacuo. The residue was dissolved again in
ꢀ
hexane (4 ml) and cooled to ꢁ20 C. Colorless crystals were obtained. The mother
liquor was removed by pipet, the product was recrystallized twice in the same manner
from hot hexane (each time from 4 ml of the solvent) and dried in vacuo to give
1
,1-diphenyl-2-bromocyclopropane 5 (3.037 g, 11.1 mmol, 93%) as colorless crystals with
ꢀ
24
ꢀ
mp 82.5-84 C (lit mp 77-79 C).
Method B: EtMgBr (2.0 ml, 1.0 M in THF, 3 mmol, 1.5 mol eq) was added to a solu-
tion of 4 (704 mg, 2 mmol) and TiCl (THF) (17 mg, 0.05 mmol, 2.5 mol.%) in dry THF
4
2
(5 ml) at room temperature over 10 min. After 10 min, water (10 ml) was added
dropwise and the organic solvent was evaporated in vacuo. The residue was mixed with
hexane (10 ml), the organic layer was separated and the water layer was extracted with
hexane (2x5 ml). The combined organic layers were dried over MgSO , filtered and
4
evaporated in vacuo to give 5 (514 mg, 1.88 mmol, 94%) as colorless crystals with

ORGANIC PREPARATIONS AND PROCEDURES INTERNATIONAL
5
ꢀ
24
ꢀ
1
mp 77-79 C (lit mp 77-79 C). H NMR (CDCl ): d 7.34-7.25 (m, 4H), 7.21-7.14 (m,
3
5
H), 7.12-7.08 (m, 1H), 3.61 (dd, 1H, J ¼ 7.8, 4.8 Hz), 1.80 (dd, 1H, J ¼ 7.8, 6.5 Hz), 1.75
13
(dd, 1H, J ¼ 6.5, 4.8 Hz). C NMR (CDCl ): d 144.3, 140.8, 130.6, 128.7, 128.3, 127.9,
3
127.3, 126.8, 36.4, 28.5, 24.0.
3
,3-Diphenylcyclopropene (1)
A solution of 1,1-diphenyl-2-bromocyclopropane 5 (2.185 g, 8 mmol) in dry THF (8 ml)
was added to a solution of tBuOK (1.796 g, 16 mmol, 2 mol eq) in dry THF (16 ml)
under an inert atmosphere of nitrogen with external cooling in an ice-water bath. The
reaction mixture was stirred at room temperature for 19 h, poured into a mixture of
ice-water (250 g) and hexane (50 ml), followed with brine (20 ml). The organic layer was
separated and the water layer was extracted with hexane (3x20 ml). The combined
organic layers were dried over Na SO , filtered and the solvent was evaporated in vacuo
2
4
1
9
to give pure 3,3-diphenylcycopropene 1 (1.520 g, 7.9 mmol, 99%) as a yellowish oil.
1
13
H NMR (CDCl ): d 7.51 (s, 2H), 7.33-7.28 (m, 4H), 7.23-7.19 (m, 6H). C NMR
3
(
CDCl ): d 147.2, 128.22, 128.20, 125.9, 113.4, 31.9.
3
Acknowledgments
This study was funded by RFBR according to the research project @ 19-03-00477. The author is
grateful to Prof. Dr. M. S. Baird (University of Wales, Bangor, UK), Prof. Dr. I. G. Bolesov
(Moscow State University, Moscow, Russia) and Prof. Dr. S. B. Tsogoeva (Friedrich-Alexander-
University of Erlangen-N u€ rnberg, Erlangen, Germany) for providing facilities to carry out the
work, as well as for fruitful discussions of the results.
ORCID
Alexey V. Nizovtsev
http://orcid.org/0000-0002-9608-1794
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