Insertion of [1.1.1]propellane into aromatic disulfides

Article abstract of DOI:10.3762/bjoc.15.114

Herein we present the synthesis of symmetrically and unsymmetrically substituted 1,3-bissulfanylbicyclo[1.1.1]pentanes from disulfides and [1.1.1]propellane. Bicyclo[1.1.1]pentanes (BCPs) recently gained interest as rigid linkers and as bioisosters of parasubstituted benzene and alkyne moieties. The most promising precursor for BCPs is [1.1.1]propellane (1). The available methods to synthesize BCPs are quite limited and many groups contribute to the development of novel methods. The insertion of 1 into disulfide bonds is known, but has never been thoroughly investigated. In this study, we show that an UV initiated radical reaction can be used to synthesize symmetrically and unsymmetrically substituted BCP sulfides by reaction of [1.1.1]propellane (1) with disulfides. Depending on the ratio of 1 to the disulfide, only the BCP product (with up to 98% yield) or a mixture of BCP and [2]staffane can be obtained. The reaction tolerates functional groups such as halogens, alkyl and methoxy groups. The separation of the corresponding BCP and [2]staffane products is challenging but possible by column chromatography and preparative TLC in most cases. Single crystal X-ray diffraction analysis confirms the rod-like structure of the [2]staffanes that is often required in material applications.

Full text of DOI:10.3762/bjoc.15.114

Insertion of [1.1.1]propellane into aromatic disulfides
Robin M. Bär1, Gregor Heinrich1, Martin Nieger2, Olaf Fuhr3 and Stefan Bräse*1,4
Full Research Paper
Open Access
Address:
Beilstein J. Org. Chem. 2019, 15, 1172–1180.
1Institute of Organic Chemistry, Karlsruhe Institute of Technology
(KIT), Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany, 2Department of
Chemistry, University of Helsinki, P.O. Box 55 (A. I. Virtasen aukio 1),
00014 University of Helsinki, Finland, 3Institute of Nanotechnology
(INT) and Karlsruhe Nano-Micro Facility (KNMF), Karlsruhe Institute
of Technology (KIT), Hermann-von-Helmholtz-Platz 1, 76344
Eggenstein-Leopoldshafen, Germany and 4Institute of Toxicology and
Genetics, Karlsruhe Institute of Technology (KIT),
doi:10.3762/bjoc.15.114
Received: 16 March 2019
Accepted: 16 May 2019
Published: 28 May 2019
Associate Editor: J. A. Murphy
Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen,
Germany
© 2019 Bär et al.; licensee Beilstein-Institut.
License and terms: see end of document.
Email:
Stefan Bräse* - braese@kit.edu
* Corresponding author
Keywords:
bicyclo[1.1.1]pentane; bioisosteres; disulfides; linkers;
[1.1.1]propellane
Abstract
Herein we present the synthesis of symmetrically and unsymmetrically substituted 1,3-bissulfanylbicyclo[1.1.1]pentanes from
disulfides and [1.1.1]propellane. Bicyclo[1.1.1]pentanes (BCPs) recently gained interest as rigid linkers and as bioisosters of para-
substituted benzene and alkyne moieties. The most promising precursor for BCPs is [1.1.1]propellane (1). The available methods to
synthesize BCPs are quite limited and many groups contribute to the development of novel methods. The insertion of 1 into disul-
fide bonds is known, but has never been thoroughly investigated. In this study, we show that an UV initiated radical reaction can be
used to synthesize symmetrically and unsymmetrically substituted BCP sulfides by reaction of [1.1.1]propellane (1) with disulfides.
Depending on the ratio of 1 to the disulfide, only the BCP product (with up to 98% yield) or a mixture of BCP and [2]staffane can
be obtained. The reaction tolerates functional groups such as halogens, alkyl and methoxy groups. The separation of the corre-
sponding BCP and [2]staffane products is challenging but possible by column chromatography and preparative TLC in most cases.
Single crystal X-ray diffraction analysis confirms the rod-like structure of the [2]staffanes that is often required in material applica-
tions.
Introduction
Rigid structures are emerging in both materials science and me- alkyne groups [5] in well-known compounds, e.g., imatinib [3]
dicinal chemistry [1]. Often referred to as bioisosteres, small and tazarotene [5]. The increase of the three-dimensionality and
strained hydrocarbons are used to replace phenyl [2-4] or the disruption of the π-system can lead to improved properties,
1172

Beilstein J. Org. Chem. 2019, 15, 1172–1180.
e.g., increased water-solubility of drug candidates [2] or the tion of 1 with nucleophiles also proceeds through a radical
electronical separation of a photoswitch and a chromophore [6]. mechanism [14,15]. The reaction with alkyl halides, initially de-
Often used moieties for these kinds of applications are trip- scribed by Michl et al. [16], has recently been further investigat-
tycenes, cubanes, bicyclo[2.2.2]octanes (BCOs) and ed by Anderson et al. (Scheme 1) [17]. Both groups showed that
bicyclo[1.1.1]pentanes (BCPs) [1]. In their pioneering work the BCP halide can be lithiated to further modify the products.
Stepan et al. replaced a para-substituted fluorophenyl ring in The opening of 1 with Grignard reagents enables the synthesis
the γ-secretase inhibitor BMS-708,163 with a BCP whereby the of aryl and some alkyl-substituted BCPs and a subsequent
oral absorption and in vitro metabolic stability could be signifi- cross-coupling reaction [5,18].
cantly increased [2]. BCPs are usually derived from
[1.1.1]propellane (1) [7]. However, the available methods to To provide bicyclo[1.1.1]pentylamine as a building block in
synthesize useful BCP building blocks are quite limited and large-scale syntheses, Bunker et al. developed a synthesis of
current research focuses on the development of such methods hydrazine BCP via a manganese-catalyzed reaction, which can
(Scheme 1).
easily be converted to the corresponding amine [19]. An alter-
native approach by Baran et al. installs the BCP late-stage at a
After the first synthesis of [1.1.1]propellane (1) by Wiberg and secondary aliphatic amine via the corresponding turbo-amide
Walker in 1982 [8] and the improved route by Szeimies et al. in [20,21]. Uchiyama et al. investigated the reaction mechanism of
1985 [9] the compound and its reactions were intensely investi- a radical multicomponent carboamination of 1. This reaction
gated [10]. Michl et al. synthesized terminally functionalized provides access to internal BCPs next to amines [22].
polymers derived from 1, so-called [n]staffanes, and discussed
their application as rigid tectones [11,12].
The reaction of 1 with thiophenol has been known since 1985
and, given the high yield, used to determine the concentration of
The characteristic reactivity of 1 emerges from the strained propellane solutions [23]. Our group investigated this reaction
central bond, which was opened with free radicals in most further and proved the generality of the thiol addition [24].
cases. The reaction with diacetyl and subsequent oxidation
leads to the important intermediate bicyclo[1.1.1]pentane-1,3- In analogy to this reaction, the insertion of 1 into disulfide
dicarboxylic acid which provides access to unsymmetrically bonds has been discovered early, but only very few examples
substituted BCPs (not shown) [13]. It is assumed that the reac- can be found in the literature [10,11,25-28].
Scheme 1: Summary of the most recent methods to obtain different BCPs from 1.
1173

Beilstein J. Org. Chem. 2019, 15, 1172–1180.
In this work, the insertion of [1.1.1]propellane (1) into disulfide detailed conditions [28]. They used diacetyldithiol and 1 to
bonds was investigated further to enable the synthesis of novel obtain bisacetylthio[n]staffanes. To find feasible conditions for
BCP building blocks. After optimizing the reaction conditions, the insertion of 1 into disulfide bonds, a screening with irradia-
the scope of the reaction was tested, followed by a proof-of- tions of different wavelengths and other reaction conditions was
concept that enables a new route to unsymmetrically substi- performed (Scheme 2). The screening reaction was set up with
tuted BCPs.
1.0 equiv of diphenyl disulfide (10a) and 1.0 equiv of 1 in
diethyl ether at room temperature and the consumption of the
starting material was monitored by GC–MS over a period of 1 h
Results and Discussion
As a starting point, [1.1.1]propellane (1) has been prepared by a (Figure 1). In this first screening approach the products were
published procedure as a solution in diethyl ether [20], quanti- not isolated. The relative conversion was determined by inte-
fied by the reaction with thiophenol [23] and stored at −78 °C. grating the signals of 10a and the products 6a and 11a. No other
Solutions of 1 were obtained with concentrations between signals were detected and the sum of the integrals was defined
0.40–0.55 M.
as 100%. This method cannot be used to determine yields or
absolute concentrations as no internal standard was added.
Optimization
As some reactions of disulfides with 1 have been reported under In the dark, no conversion could be observed at all. The expo-
different conditions we decided to compare and tune these sure to daylight led to a conversion of less than 10% after 1 h.
conditions. Szeimies et al. used azobisisobutyronitrile (AIBN) With a 500 W halogen lamp, 90% of the starting material was
as a radical initiator and heated the reaction mixture in a Carius consumed after 1 h. By the addition of di-tert-butyl peroxide
tube to 80 °C [27]. Wiberg et al. initiated the reaction by irradi- (DTBP) as a radical initiator, the conversion could be acceler-
ation with a 60 W light bulb overnight [10]. Michl et al. were ated in the beginning of the measurement. However, after the
the first to use UV irradiation in this reaction, but did not report work-up of the reaction with radical initiator, an insoluble white
Scheme 2: Screening reaction performed with different types of irradiation (see Figure 1).
Figure 1: Optimization of the reaction conditions. The relative conversion was determined by GC–MS. The use of a radical initiator (di-tert-butyl
peroxide, DTBP) led to increased amounts of insoluble polymer.
1174

Beilstein J. Org. Chem. 2019, 15, 1172–1180.
solid, presumably longer [n]staffanes, was discovered. When The analysis of compound 6a by single-crystal X-ray diffrac-
the reaction was performed in a 500 W UV reactor (medium- tion [29] revealed a distance of 1.844(3) Å between the bridge-
pressure mercury-vapor lamps, 254 nm) without a radical initia- head carbons of the BCP unit (Figure 2).
tor almost full conversion (≈90%) was observed after 15 min.
The use of UV light at room temperature seemed feasible and
the conversion was faster than reported by Wiberg et al. [10].
The absence of a radical initiator is advantageous as the forma-
tion of longer [n]staffanes is usually promoted by the initiators.
After this initial screening a reaction time of 20 min was
chosen.
Scope and limitations
The ratio of the products 6a and 11a could easily be changed by
Figure 2: Molecular structure of 6a (displacement parameters are
drawn at 50% probability level), distance C1–C3 1.844(3) Å.
the amount of disulfide used in the reaction. We found that
3.0 equiv of the disulfide led to almost exclusive formation of
6a (Table 1, entry 1). These conditions were applied to differ-
ent aromatic disulfides and the corresponding products were ob- When 2.0 equiv of 1 and 1.0 equiv of 10a were used, the yield
tained in fair to quantitative yields. The high yields for the of 6a dropped dramatically and the [2]staffane product 11a was
BCPs 6 highlight the advantage of this mild method. Wiberg et obtained in poor yield (Table 1, entry 3). The separation was
al. reported a yield of 45% for 6a [10] and Szeimies et al. ob- possible by preparative TLC. It is assumed that longer staffane
tained 63% of 6a and 27% of 11a [27]. Halogen substitutions chains are formed in this reaction. However, the isolation and
were tolerated as well as methyl and methoxy groups. All prod- characterization of these compounds was not successful. The in-
ucts of substituted aromatic disulfides are previously unre- fluence of the ratio of 1:10 on the formation of the [2]staffane
ported.
was also investigated for some of the substituted disulfides. The
Table 1: Results of the insertion of 1 into aromatic disulfide bonds. The ratio of 1:10 determines the amount of [2]staffane formed.
Entry
Disulfide 10
R
Ratio of 1:10
Yield 6 [%]
Yield 11 [%]
1
10a
10a
10a
10a
10b
10b
10c
10c
10d
10d
10e
10f
H
1:3
1:1
2:1
3:1
1:3
2:1
1:3
2:1
1:3
2:1
1:3
1:3
98a
51c
32c
33c
98a
34c
96a
34c
96a
35c
94a
61a
–b
2
H
5c
3
H
10c
20c
–b
4
H
5
4-Cl
4-Cl
3,5-Cl2
3,5-Cl2
4-Me
4-Me
4-OMe
2-Ph
6
15c
–b
7
8
8c
9
traces
12c
traces
–b
10
11
12
aIsolated yield, purified by column chromatography. bNot observed. cIsolated yield, purified by preparative TLC.
1175

Beilstein J. Org. Chem. 2019, 15, 1172–1180.
overall trend was the same for all reactions with yields of Insertion into aliphatic disulfides
around 35% for 6 and between 8–15% for 11. The yield of 11a To investigate the insertion of 1 into aliphatic disulfides, benzyl
could be increased to 20% by using a ratio of 3:1 (Table 1, entry disulfide 12 was chosen as a model compound. As the forma-
4).
tion of thiyl radicals is critical to the reaction and most aliphat-
ic disulfides do not absorb UV light at the used wavelength,
The radical reaction as proposed in Scheme 3 should lead to radical initiators should be taken into account for other disul-
higher yields of 11 with an increasing amount of 1. As the fides. However, for 12 the reaction was successful without
kinetically controlled reactions depend on the concentration of radical initiator and the BCP 13 was obtained as the main prod-
the reaction partners, the dimerization becomes less dominant uct (Scheme 4). The purification was possible by HPLC
with a low concentration of the BCP radical. The propagation (reversed-phase) and the yield was significantly lower com-
with the disulfide proceeds faster as the disulfide concentration pared to the aromatic disulfides. Szeimies et al. also synthe-
is higher. The formation of staffanes seems to be less favored sized alkyl-substituted BCP and staffane sulfides with the previ-
than the propagation with the disulfide. This observation is in ously described method (see optimization) in similar yields
accordance with previous calculations and experimental results [27]. Presumably, there are two factors contributing to the
[17,22].
lowered yield. The bond dissociation energy (BDE) of dialkyl-
Scheme 3: Proposed mechanism of the propellane insertion into disulfide bonds.
Scheme 4: The insertion of 1 into dibenzyl disulfide (12) led to the formation of BCP 13 and traces of [2]staffane 14. The structure of 14 could be
proven by single-crystal X-ray diffraction (displacement parameters are drawn at 50% probability level).
1176

Beilstein J. Org. Chem. 2019, 15, 1172–1180.
disulfides is higher than the BDE of diaryl disulfides [30]. product mixture with the ratio 1:2:1 would be expected. The ob-
Therefore lower concentrations of thiyl radicals are present to tained yields of 18, 45 and 24%, respectively differ slightly
initiate the reaction. The second reason could be the absorption from this ratio.
of the UV irradiation. In the benzyl group only the aromatic part
can absorb the light and a transfer has to take place to promote To facilitate the separation of the products we switched the
the homolytic cleavage of the disulfide.
disulfides used in this reaction to 10a and 10e (Scheme 6). With
the bigger difference in polarity of the substituents, the prod-
In first purification attempts [2]staffane 14 could be identified ucts 6a, 16 and 6e could be separated by column chromatogra-
in a mixture with 13 in traces. From the product mixture we phy and preparative TLC. Again, we observed a deviation from
could obtain single-crystals of 14 to confirm the structure by the expected product ratio. This leads to the assumption that the
X-ray diffraction (Scheme 4) [31]. The rod-like structure of the 4-methoxybenzenethiyl radical is either formed faster and/or
[2]staffane unit now becomes more tangible. The distance in reacts more rapidly with 1 than the corresponding benzenethiyl
one BCP unit equals 1.857(3) Å (C1–C5) and the two units are radical. The calculated BDE (DFT calculation) of 10e is slightly
1.491(4) Å apart from each other (C1–C1’).
lower with 49.0 kcal/mol compared to 10a with 54.5 kcal/mol
[32]. This difference hints towards the faster formation of the
4-methoxybenzenethiyl radical, but the values are in the same
Reaction with different mixtures of disulfides
The synthesis of useful unsymmetrically substituted BCPs region. To ascertain the main factor for this trend further inves-
remains a challenge and only few direct routes from 1 are avail- tigations are necessary. We observed the same trend in the thiol
able (see Introduction). The insertion into disulfides could addition to 1, when thiophenol and 4-methoxythiophenol were
provide an alternative approach. With the two disulfides 10a used in a competitive reaction [24].
and 10d as starting materials a product mixture of 6a, 15 and 6d
was obtained (Scheme 5). The yields were determined by NMR The structure of 16 could be confirmed by single-crystal X-ray
spectroscopy as the products could not be separated by column diffraction [33]. With 16 as the main product of this reaction,
chromatography (Figure 3). Analytical samples could be ob- this method provides new access to unsymmetrically substi-
tained by purification of this mixture via HPLC (reversed-phase tuted BCPs directly from 1 and purely symmetrical starting ma-
column). If one assumes equal reaction rates for the propellane terials. This finding will be pursued with a selective cleavage or
insertion, independent from the substitution of the disulfide, a oxidation of one sulfide in further studies.
Scheme 5: Reaction of propellane (1) with the two disulfides 10a and 10d. When two different disulfides were used, all three possible products were
obtained. The yields were determined by NMR spectroscopy (Figure 3).
1177

Beilstein J. Org. Chem. 2019, 15, 1172–1180.
Figure 3: NMR spectra of pure 6a (green) and 6d (red) and the obtained mixture with the new compound 15 (blue).
Scheme 6: The reaction of 1 with the two disulfides 10a and 10e led to the known products 6a, 6e and to the unsymmetrically substituted BCP 16 as
the main product. The compounds could be separated by column chromatography and preparative TLC. The structure of 16 could be confirmed by
single-crystal X-ray diffraction (displacement parameters are drawn at 50% probability level).
1178

Beilstein J. Org. Chem. 2019, 15, 1172–1180.
Conclusion
inspiring discussions about reaction kinetics. We acknowledge
The reported reaction of [1.1.1]propellane with aromatic and to the support by two projects of the German Research Founda-
a certain extend aliphatic disulfides provides access to tion, namely BR 1750/34-1 (use of the electronic lab notebook
[2]staffanes and symmetrical and unsymmetrical BCPs. The and repository Chemotion to disclose the herein described
separation of these compounds is often challenging due to the research data) and BR1750/40-1, JU2909/5-1 (service for the
similar polarity. However, the reaction conditions can be tuned deposit of physical samples of the isolated compounds).
to obtain solely the BCP compound in high yields. By mixing
ORCID® iDs
Robin M. Bär - https://orcid.org/0000-0002-5122-7809
two aromatic disulfides in this reaction three different products
can be obtained, with the unsymmetrically substituted com-
Olaf Fuhr - https://orcid.org/0000-0003-3516-2440
pound as the main product. This method will become particular-
Stefan Bräse - https://orcid.org/0000-0003-4845-3191
ly interesting if the two sulfides of the product can be modified
individually. This approach to unsymmetrically substituted
References
1. Locke, G. M.; Bernhard, S. S. R.; Senge, M. O. Chem. – Eur. J. 2019,
BCPs will be further investigated.
25, 4590–4647. doi:10.1002/chem.201804225
2. Stepan, A. F.; Subramanyam, C.; Efremov, I. V.; Dutra, J. K.;
Supporting Information
O’Sullivan, T. J.; DiRico, K. J.; McDonald, W. S.; Won, A.; Dorff, P. H.;
Full experimental details and analytical data (1H NMR,
13C NMR, X-ray analysis) are provided in the following
files.
Nolan, C. E.; Becker, S. L.; Pustilnik, L. R.; Riddell, D. R.;
Kauffman, G. W.; Kormos, B. L.; Zhang, L.; Lu, Y.; Capetta, S. H.;
Green, M. E.; Karki, K.; Sibley, E.; Atchison, K. P.; Hallgren, A. J.;
Oborski, C. E.; Robshaw, A. E.; Sneed, B.; O’Donnell, C. J.
J. Med. Chem. 2012, 55, 3414–3424. doi:10.1021/jm300094u
3. Nicolaou, K. C.; Vourloumis, D.; Totokotsopoulos, S.; Papakyriakou, A.;
Karsunky, H.; Fernando, H.; Gavrilyuk, J.; Webb, D.; Stepan, A. F.
ChemMedChem 2016, 11, 31–37. doi:10.1002/cmdc.201500510
4. Measom, N. D.; Down, K. D.; Hirst, D. J.; Jamieson, C.; Manas, E. S.;
Patel, V. K.; Somers, D. O. ACS Med. Chem. Lett. 2017, 8, 43–48.
doi:10.1021/acsmedchemlett.6b00281
Supporting Information File 1
Description and analyses.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-15-114-S1.pdf]
Supporting Information File 2
Spectra.
5. Makarov, I. S.; Brocklehurst, C. E.; Karaghiosoff, K.; Koch, G.;
Knochel, P. Angew. Chem., Int. Ed. 2017, 56, 12774–12777.
doi:10.1002/anie.201706799
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-15-114-S2.pdf]
6. de Meijere, A.; Zhao, L.; Belov, V. N.; Bossi, M.; Noltemeyer, M.;
Hell, S. W. Chem. – Eur. J. 2007, 13, 2503–2516.
doi:10.1002/chem.200601316
Supporting Information File 3
RInChIs.
7. Dilmaç, A. M.; Spuling, E.; de Meijere, A.; Bräse, S.
Angew. Chem., Int. Ed. 2017, 56, 5684–5718.
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-15-114-S3.xlsx]
doi:10.1002/anie.201603951
8. Wiberg, K. B.; Walker, F. H. J. Am. Chem. Soc. 1982, 104, 5239–5240.
doi:10.1021/ja00383a046
Supporting Information File 4
DOIs data repository.
9. Semmler, K.; Szeimies, G.; Belzner, J. J. Am. Chem. Soc. 1985, 107,
6410–6411. doi:10.1021/ja00308a053
10.Wiberg, K. B.; Waddell, S. T. J. Am. Chem. Soc. 1990, 112,
2194–2216. doi:10.1021/ja00162a022
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-15-114-S4.xlsx]
11.Kaszynski, P.; Friedli, A. C.; Michl, J. J. Am. Chem. Soc. 1992, 114,
601–620. doi:10.1021/ja00028a029
Supporting Information File 5
Reference samples molecule archive.
12.Kaszynski, P.; Michl, J. J. Am. Chem. Soc. 1988, 110, 5225–5226.
doi:10.1021/ja00223a070
[https://www.beilstein-journals.org/bjoc/content/
supplementary/1860-5397-15-114-S5.xlsx]
13.Kaszynski, P.; Michl, J. J. Org. Chem. 1988, 53, 4593–4594.
doi:10.1021/jo00254a038
14.Rehm, J. D.; Ziemer, B.; Szeimies, G. Eur. J. Org. Chem. 1999,
2079–2085.
doi:10.1002/(sici)1099-0690(199909)1999:9<2079::aid-ejoc2079>3.3.c
o;2-4
Acknowledgements
15.Levin, M. D.; Kaszynski, P.; Michl, J. Chem. Rev. 2000, 100, 169–234.
doi:10.1021/cr990094z
R.M.B. acknowledges the SFB 1176 funded by the German
Research Foundation (DFG) in the context of projects A4 & B3
for funding. We thank A. Dilmac and N. Griebenow for initial
experiments and advice and Prof. Matthias Olzmann (KIT) for
16.Kaszynski, P.; McMurdie, N. D.; Michl, J. J. Org. Chem. 1991, 56,
307–316. doi:10.1021/jo00001a058
1179

Beilstein J. Org. Chem. 2019, 15, 1172–1180.
17.Caputo, D. F. J.; Arroniz, C.; Dürr, A. B.; Mousseau, J. J.;
Stepan, A. F.; Mansfield, S. J.; Anderson, E. A. Chem. Sci. 2018, 9,
5295–5300. doi:10.1039/c8sc01355a
License and Terms
This is an Open Access article under the terms of the
Creative Commons Attribution License
18.Messner, M.; Kozhushkov, S. I.; de Meijere, A. Eur. J. Org. Chem.
2000, 1137–1155.
doi:10.1002/1099-0690(200004)2000:7<1137::aid-ejoc1137>3.0.co;2-2
19.Bunker, K. D.; Sach, N. W.; Huang, Q.; Richardson, P. F. Org. Lett.
2011, 13, 4746–4748. doi:10.1021/ol201883z
(http://creativecommons.org/licenses/by/4.0). Please note
that the reuse, redistribution and reproduction in particular
requires that the authors and source are credited.
20.Gianatassio, R.; Lopchuk, J. M.; Wang, J.; Pan, C.-M.; Malins, L. R.;
Prieto, L.; Brandt, T. A.; Collins, M. R.; Gallego, G. M.; Sach, N. W.;
Spangler, J. E.; Zhu, H.; Zhu, J.; Baran, P. S. Science 2016, 351,
241–246. doi:10.1126/science.aad6252
The license is subject to the Beilstein Journal of Organic
Chemistry terms and conditions:
21.Lopchuk, J. M.; Fjelbye, K.; Kawamata, Y.; Malins, L. R.; Pan, C.-M.;
Gianatassio, R.; Wang, J.; Prieto, L.; Bradow, J.; Brandt, T. A.;
Collins, M. R.; Elleraas, J.; Ewanicki, J.; Farrell, W.; Fadeyi, O. O.;
Gallego, G. M.; Mousseau, J. J.; Oliver, R.; Sach, N. W.; Smith, J. K.;
Spangler, J. E.; Zhu, H.; Zhu, J.; Baran, P. S. J. Am. Chem. Soc. 2017,
139, 3209–3226. doi:10.1021/jacs.6b13229
(https://www.beilstein-journals.org/bjoc)
The definitive version of this article is the electronic one
which can be found at:
doi:10.3762/bjoc.15.114
22.Kanazawa, J.; Maeda, K.; Uchiyama, M. J. Am. Chem. Soc. 2017, 139,
17791–17794. doi:10.1021/jacs.7b11865
23.Mondanaro, K. R.; Dailey, W. P. Org. Synth. 1998, 75, 98–105.
doi:10.15227/orgsyn.075.0098
24.Bär, R. M.; Kirschner, S.; Nieger, M.; Bräse, S. Chem. – Eur. J. 2018,
24, 1373–1382. doi:10.1002/chem.201704105
25.Wiberg, K. B.; Waddell, S. T.; Laidig, K. Tetrahedron Lett. 1986, 27,
1553–1556. doi:10.1016/s0040-4039(00)84310-5
26.Wiberg, K. B.; Waddell, S. T. Tetrahedron Lett. 1988, 29, 289–292.
doi:10.1016/s0040-4039(00)80076-3
27.Bunz, U.; Polborn, K.; Wagner, H.-U.; Szeimies, G. Chem. Ber. 1988,
121, 1785–1790. doi:10.1002/cber.19881211014
28.Friedli, A. C.; Kaszynski, P.; Michl, J. Tetrahedron Lett. 1989, 30,
455–458. doi:10.1016/s0040-4039(00)95226-2
29.CCDC 1896780 (6a) contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via
http://www.ccdc.cam.ac.uk/data_request/cif.
30.Luo, Y.-R. Handbook of bond dissociation energies in organic
compounds; CRC press: Boca Raton, Florida, USA, 2002.
doi:10.1201/9781420039863
31.CCDC 1896794 (14) contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via
http://www.ccdc.cam.ac.uk/data_request/cif.
32.Yang, Y.-M.; Yu, H.-Z.; Sun, X.-H.; Dang, Z.-M. J. Phys. Org. Chem.
2016, 29, 6–13. doi:10.1002/poc.3480
33.CCDC 1908215 (16) contains the supplementary crystallographic data
for this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via
http://www.ccdc.cam.ac.uk/data_request/cif.
1180