When Gold Meets Perfumes: Synthesis of Olfactive Compounds via Gold-Catalyzed Cycloisomerization Reactions

Article abstract of DOI:10.1021/acs.orglett.0c00843

An efficient, and mild synthetic route for the preparation of functionalized volatile oxa-bicyclo[4.1.0]-hept-4-ene (29 compounds, 44-98% isolated yields) has been developed relying on the association of IPrAuCl with NaBArF. The remarkable selectivity was demonstrated on a 1 g and 25 g scale with low catalyst loadings. The synthetic utility of these low-molecular-weight enols was further demonstrated by the derivatization of some adducts and by the unprecedented olfactory evaluation of all bicyclic derivatives.

Full text of DOI:10.1021/acs.orglett.0c00843

pubs.acs.org/OrgLett
Letter
When Gold Meets Perfumes: Synthesis of Olfactive Compounds via
Gold-Catalyzed Cycloisomerization Reactions
́
Romain Laher, Christophe Marin, and Veronique Michelet*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c00843
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: An efficient, and mild synthetic route for the preparation of functionalized volatile oxa-bicyclo[4.1.0]-hept-4-ene (29
compounds, 44−98% isolated yields) has been developed relying on the association of IPrAuCl with NaBArF. The remarkable
selectivity was demonstrated on a 1 g and 25 g scale with low catalyst loadings. The synthetic utility of these low-molecular-weight
enols was further demonstrated by the derivatization of some adducts and by the unprecedented olfactory evaluation of all bicyclic
derivatives.
he recent upsurge of interest in exploring new flavors and
fragrances of 3D molecular structures has driven the need
for synthetic robust methodologies that can generate original
scaffolds from acyclic precursors in a single step.1 Among them,
cyclopropanes represent a privileged scaffold, such as
exemplified in Figure 1,2 with natural (+)-thujone having a
such skeletons have been developed, but to the best of our
knowledge, most of them have scarcely relied on nontoxic metals
such as gold.1 Alternatively, gold-catalyzed reactions have been
recognized as powerful methods to prepare polycyclic
molecules,3 and some scarce examples have been described
toward the synthesis or approaches of thujone or sabinene
derivatives.4
T
In a continuation of our ongoing program on the construction
of heterocycles and bicyclic molecules via a gold-catalyzed
process,5 we wondered if we could find an efficient and selective
catalyst for cycloisomerization reactions of volatile oxygen-
tethered 1,6-enynes (Scheme 1). We therefore wish to describe
our preliminary results on the synthetic methodology for the
synthesis of new functionalized oxa-bicyclo[4.1.0]-hept-4-enes
of high interest for the preparation of novel odorant molecules
and their unprecedented olfactory evaluation by perfumers.
Seminal contributions appeared in 1995 and 1996, respectively,
when Blum and Murai’s groups described an unprecedented
PtCl4- and PtCl2-catalyzed cycloisomerization reaction of allyl
propynyl ethers, leading to oxabicyclo[4.1.0]heptenes.6 These
Figure 1. Selected examples of fragrance ingredients bearing cyclo-
propane moieties.
Received: March 5, 2020
menthol odor, sabinene having a spicy black pepper odor, and
gurjunene as well as synthetic derivatives such as javanol or
serenolide, having, respectively, sandalwood and white musk
odors with sweet, fruity connotations.
Considering the interest in creating original fragrances and to
respond to European regulations, numerous strategies targeting
https://dx.doi.org/10.1021/acs.orglett.0c00843
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
yield, even though the conversion was high (entries 5−7). The
commercially available XPhosAu(MeCN)SbF6 afforded the
desired derivative 2a in 60% yield in DCM, whereas low or no
conversion was observed in another solvent (entries 8−10).
Switching to NHC-functionalized gold complexes3,10 was more
rewarding because we could isolate the desired compound in
higher yield and with higher selectivity (entries 11−15).
Pleasingly, the use of NaBArF, in place of silver salt, for the
abstraction of chloride on gold(I) catalyst, was found to be
smooth enough to generate the active catalyst without
Scheme 1. Our Strategy to Construct oxa-bicyclo[4.1.0]-
Hept-4-ene via Au-Catalyzed Cycloisomerization
̈
promoting the formation of a residual Bronsted catalyst (entries
pioneer examples were then followed by several comprehensive
studies involving other carbophilic complexes such as platinum,
iridium, rhodium, or gold.7,8 Nevertheless, most of the examples
relied on nitrogen-tethered derivatives or, in the case of oxygen
examples, mainly on heavy aromatic functionalized derivatives.
We therefore initiated this study by investigating the reaction of
model enyne 1a in the presence of different catalyst/solvent
combinations. The results are summarized in Table 1. On the
basis of our previous gold-catalyzed experience, we first tested
the (PPh3)AuNTf2 catalyst in dichloromethane at room
temperature (entry 1). The reaction led to full conversion after
5 h with only 1 mol % catalyst, but a mixture of 2a/3a was
observed in a 1:0.8 ratio. The formation of 3a could be explained
by a favored carbophilic gem-dimethyl carbon, allowing the
elimination of a proton to form a 1,4-diene.9
12−17). We managed to perform the reaction in the presence of
2 mol % catalyst at 60 °C, allowing the exclusive formation of 2a
within 1 h in 90% isolated yield (entry 17). With a set of
optimized conditions in hand, the scope and generality of this
mild protocol were explored. We therefore selected the reaction
conditions, implying 2 mol % of IPrAuCl and 2 mol % of NaBArF
in toluene at 60 °C. For this purpose and to broaden the
functionalities amenable on odorant molecules, we synthesized
various ethers 1b−v by the classical Williamson reactions
(Scheme 2, Supporting Information).
Scheme 2. Synthesis of Enyne Ethers
We tried to find other Lewis acid catalysts that would have a
better activity than gold, such as bismuth, ytterbium, copper,
platinum, or iron complexes, but no significant activity was
observed. We therefore decided to optimize the reaction
conditions in the presence of gold complexes and screened
various precatalysts and solvents. The Au(III) catalysts and their
monocationic forms led to a small amount of desired bicyclic
compounds and low conversions (entries 2−4). We thus focused
on Au(I) catalysts and first observed that the use of a [PPh3Au]+
complex in THF, DCM, or toluene did not lead to 2a in good
Anticipating various olfactive differences between bicyclic
adducts, we introduced methyl, phenyl, and alkyl groups at
various positions between the alkenyl and alkynyl moieties,
allowing various substituents on the resulting cyclopropane. We
a
Table 1. Optimization of Reaction Conditions
b
b
b
entry
catalyst (5 mol %)
solvent
conv (%) /time (h)
yield 2a (%)
yield 3a (%)
1
2
PPh3AuNTf2
PicAuCl2
PicAuCl2/AgSbF6
Pyr(AuCl3)/AgSbF6
(PPh3)AuNTf2
PPh3AuCl/AgSbF6
PPh3AuCl/AgSbF6
XPhosAu(MeCN)SbF6
XPhosAu(MeCN)SbF6
XPhosAu(MeCN)SbF6
IPrAu(MeCN)BF4
IPrAuCl/AgOTf
IPrAuCl/AgSbF6
IPrAuCl/AgSbF6
IPrAuCl/NaBArF
IPrAuCl/NaBArF
IPrAuCl/NaBArF
DCM
DCM
DCM
DCM
THF
DCM
toluene
THF
DCM
toluene
DCM
DCM
DCM
toluene
toluene
DCM
toluene
100/20
24/96
40
16
0
0
0
21
trace
NR
60
11
33
trace
14
0
28
c
d
3
4
100/20
c
d
34/20
e
5
6
7
8
100/17
d
90/20
10
d
100/2
trace
NR
0
0/4
e
9
100/20
18/20
77/96
98/1
99/0.5
100/3
100/2
100/2
100/1
10
11
12
13
14
15
16
57
13
trace
15
0
5
0
51 (20)
59 (32)
74 (65)
93 (82)
95 (90)
0
0
f g
17 ,
a
Reaction conditions: Au complex (0.5−5 mol %) and enyne 1a (1−3 mmol) were stirred in a screw-capped tube in a solvent under an argon
b
c
d
e
f
g
1
atmosphere. Determined by crude H NMR analysis. Au/Ag 1:1. Degradation. Isolated yield. 60 °C. 2 mol %. NR: no reaction.
B
https://dx.doi.org/10.1021/acs.orglett.0c00843
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
also prepared ester-functionalized derivatives 1m and 1o as well
as allyl and benzyl derivatives 1n and 1p. Some aryl-
functionalized 1,6-enynes 1q−v were also synthesized bearing
bromide, ester, and cyano groups, with the bromo groups being
designed for postfunctionalization. We next evaluated the scope
and limitations of enynes 1b−v, and the results are summarized
in Scheme 3.
most of them being limited to C−O and C−N bond
formations.12
We selected 2t and 2g for postfunctionalization reactions, as
described in Scheme 5. The bromo-derivative 2t was trans-
Scheme 5. Post-Functionalization Reactions
Scheme 3. Scope of the Au-Catalyzed Cycloisomerization
Reaction
formed to lighter alcohols 4 in 69% yield by preparing the
Grignard reagent and quenching with acetone and cyclo-
butanone. The enol ether 2g was reduced in the presence of
triethylsilane, leading to bicyclic tetrahydrofuran 5 in 91% yield.
Itwas also oxidizedby ozonolysis, leading to aldehyde6in agood
71% yield and then reacted smoothly with camphorsulfonic acid
in methanol to give ketal 7 in 62% yield. Ketals 8a and 8b were
obtained from 2g in a 1:0.62 ratio and separated with 73% yield.
The olfactory properties of the prepared oxa-bicyclo[4.1.0]-
hept-4-enes 2a−o, as well as the derivatized 4−8a were
determined (Scheme 6). The compounds were evaluated in
The phenylethynyl derivatives 1b, 1d, 1f, and 1g led to the
corresponding bicyclic adducts 2b, 2d, 2f, and 2g in 65−98%
isolated yield. The alkylethynyl bearing a cinnamyl side chain 1c
led to the cyclized product 2c in 48% yield. The volatile alkyl-
substituted derivatives 2h−l were nicely prepared and isolated in
74−91% yield. It is noteworthy that in the case of 2h and 2i, only
0.2 mol % of catalyst was engaged. Polar functions such as
carbonate or ester groups were compatible with the reaction
conditions, as the bicyclic adducts 2m and 2o were isolated in
moderate yield. The presence of benzyl and functionalized aryl
groups was authorized considering the good to excellent yields in
the formation of 2p−v. One challenge in catalytic reactions is the
scale up of the conditions. To our delight, the cycloisomerization
of the bromo-substituted ether 1t could be performed in the
presence of 0.1 mol % of gold catalyst and on a 1 g scale (Scheme
4). The bicyclic ether 2t was isolated in 95% yield. The catalyst
loading was further decreased to 0.04 mol % and led to bicycle 2g
in 96% distilled yield on a 25 g scale, which makes these examples
part of the rare reports in the literature11 concerning high
turnover numbers (TON = 950 and 2400, respectively), with
Scheme 6. Olfactory Properties
Scheme 4. Scale-up Reaction
C
https://dx.doi.org/10.1021/acs.orglett.0c00843
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
solution, classically at 10% in dipropylene glycol. Globally, the
bicyclic adducts were characterized by very diverse and
unpredictable notes,13 with green, fruity, and floral nuances.
The presence of a phenyl group enhanced the floral and fruity
note (2c,d, 2f,g), whereas the alkyl groups favored the greenish
intense note (2h,i, 2l). Interestingly, one may notice that the
increase in the length of the side alkyl chain enhances the floral
nuance (2h versus 2l). The presence of ester or alkenyl
functional groups (2m−o) was very interesting because it
proposed a different musky or floral profile. The floral and fruity
note aspect was lost when a substituent was introduced on the
aromatic ring (4), most probably because of the nonvolatility of
the bicyclic adduct. The importance of the bicyclic skeleton was
demonstrated considering the odorless properties of cyclo-
propane 6 and the rhubarb odor of bicyclic adduct 5. A smaller
bicyclic ring (7) also allowed a green tone, whereas a ketal
function such as in 8a altered the observed sensations for 2c,d
and 2f. Pleasingly, because fragrances are related to known
memories, compounds 4e, 2n, and 5 presented notes related to
known synthetic perfumes such as Hexalon, Hyacinth Body, and
Rhubafuran, respectively.1,2,13
To conclude, astraightforward approachtoaccess volatile oxa-
bicyclo[4.1.0]-hept-4-enes is described. This strategy involves
the Au-catalyzed cycloisomerization reaction of oxygen-tethered
enynes in the presence of IPrAuCl as a catalyst and NaBArF as a
cocatalyst. The reaction conditions were compatible with alkyl-
substituted enynes and allowed the formation of low-molecular-
weight bicyclic derivatives suitable for applications in the flavor
and fragrances area. Furthermore, this expeditious process was
applied on a 1 g scale as well as a 25 g scale with a low catalyst
loading, allowing the formation of new functionalized oxa-
bicyclo[4.1.0]-hept-4-ene in excellent yield. Further functional-
ization gave rise to the introduction of an alcohol, reduction of
enol to pyran, and oxidation via ozonolysis. The comparison of
olfactory properties showed interesting properties for bicyclic
adducts bearing n-propyl and ethyl groups. It also highlighted the
difficulty of predictability in the field of fragrances. Further
challenging applications of this method are underway in our
laboratory, especially in regards to the access to chiral bicyclic
derivatives.
https://pubs.acs.org/10.1021/acs.orglett.0c00843
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
This workwas supported by the Centre National de la Recherche
Scientifique (CNRS) and the University Cote d’Azur. We
gratefully acknowledge Expressions Parfumees for a grant to R.L.
This study was partly supported by research funding from the
̂
́
̂
́
Canceropole PACA, Institut National du Cancer, and Region
́
Sud. We are also grateful toJennifer Buzzi, Stephane Coez, Diane
́
́
Galmiche, and Celine Ripert (Expressions Parfumees, Grasse)
for the determination of the olfactory properties.
REFERENCES
■
(1) (a) The Chemistry of Fragrances: From Perfumer to Consumer; Sell,
C. S., Ed.; RSC Publishing, Ltd.: Cambridge, U.K., 2006. (b) Sell, C. S.
Chemistry and the Sense of Smell; John Wiley & Sons Ltd.: Hoboken, NJ,
2014. (c) Ohloff, G.; Pickenhagen, W.; Kraft, P. Scent and Chemistry;
Wiley-VCH Verlag GmbH & Co. KGaA: Weinheim, Germany, 2012.
(d) Narula, A. P. S. The search for new fragrance ingredients for
functional perfumery. Chem. Biodiversity 2004, 1, 1992. (e) Frater, G.;
Bajgrowicz, J. A.; Kraft, P. Tetrahedron 1998, 54, 7633.
(2) (a) Lawrence, B. M. Perfum. Flavor. 2001, 26, 25. (b) Williams, J.
D.; Yazarians, J. A.; Almeyda, C. C.; Anderson, K. A.; Boyce, G. R. J.
Agric. Food Chem. 2016, 64, 4319. (c) Menon, A. N.; Padmakumari, K.
P. J. J. Essent. Oil Res. 2005, 17, 153. (d) Lawrence, B. M. Perfum. Flavor.
̈
2002, 27, 48. (e) Schroder, F. Chem. Biodiversity 2014, 11, 1734.
(f) Bajgrowicz, J. A.; Frater, G.; Givaudan. European Patent 0801049,
1997. (g) Kraft, P.; Cadalbert, R. European Patent 1262474, 2001.
(3) (a) Modern Gold Catalyzed Synthesis; Toste, F. D., Hashmi, A. S. K.,
Ed.; Wiley-VCH: Weinheim, Germany, 2012. (b) Gold Catalysis: An
Homogeneous Approach; Toste, F. D., Michelet, V., Eds.; Imperial
College Press: London, 2014. (c) The Chemistry of Organogold
Compounds. In Patai’s Chemistry of Functional Groups; Rappoport, Z.,
Liebman, J. F., Marek, I., Eds.; John Wiley & Sons, Inc.: Hoboken, NJ,
2014. (d) Homogeneous Gold Catalysis. In Topics in Current Chemistry;
Slaughter, L. M., Ed.; Springer: Berlin, 2015. (e) Brill, M.; Nolan, S. P.
Top. Organomet. Chem. 2015, 62, 51−90.
(4) (a) Furstner, A.; Schlecker, A. Chem. - Eur. J. 2008, 14, 9181.
̈
(b) Fehr, C.; Vuagnoux, M.; Buzas, A.; Arpagaus, J.; Sommer, H. Chem. -
Eur. J. 2011, 17, 6214. (c) Mamane, V.; Gress, T.; Krause, H.; Furstner,
A. J. Am. Chem. Soc. 2004, 126, 8654. (d) Harrak, Y.; Blaszykowski, C.;
ASSOCIATED CONTENT
* Supporting Information
■
̈
sı
̀
Bernard, M.; Cariou, K.; Mainetti, E.; Mouries, V.; Dhimane, A.-L.;
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c00843.
Fensterbank, L.; Malacria, M. J. Am. Chem. Soc. 2004, 126, 8656.
(5) (a) Arcadi, A.; Chiarini, M.; Del Vecchio, L.; Marinelli, F.;
Michelet, V. Eur. J. Org. Chem. 2017, 2017, 2214. (b) Tomas-Mendivil,
E.; Heinrich, C.; Ortuno, J.-C.; Starck, J.; Michelet, V. ACS Catal. 2017,
7, 380. (c) Arcadi, A.; Chiarini, M.; Del Vecchio, L.; Marinelli, F.;
Michelet, V. Chem. Commun. 2016, 52, 1458. (d) Arcadi, A.;
Pietropaolo, E.; Alvino, A.; Michelet, V. Org. Lett. 2013, 15, 2766.
(e) Mariaule, G.; Newsome, G.; Toullec, P. Y.; Belmont, P.; Michelet, V.
Experimental procedures, analytical data, and NMR
spectra for all compounds (PDF)
AUTHOR INFORMATION
Corresponding Author
■
̀
Org. Lett. 2014, 16, 4570. (f) Bontemps, A.; Mariaule, G.; Desbene-
Finck, S.; Helissey, P.; Giorgi-Renault, S.; Michelet, V.; Belmont, P.
Synthesis 2016, 48, 2178. (g) Tang, Y.; Benaissa, I.; Huynh, M.; Vendier,
́
̂
Veronique Michelet − University Cote d’Azur, Institut de Chimie
de Nice, Nice 06108 CEDEX 2, France; orcid.org/0000-
0002-2217-9115; Email: veronique.michelet@univ-
cotedazur.fr
́
L.; Lugan, N.; Bastin, S.; Belmont, P.; Cesar, V.; Michelet, V. Angew.
Chem., Int. Ed. 2019, 58, 7977. (h) Chen, X.; Martini, S.; Michelet, V.
Adv. Synth. Catal. 2019, 361, 3612.
Authors
(6) (a) Blum, J.; Beer-Kraft, H.; Badrieh, Y. J. Org. Chem. 1995, 60,
5567. (b) Chatani, N.; Furukawa, N.; Sakurai, H.; Murai, S.
Organometallics 1996, 15, 901.
̂
Romain Laher − University Cote d’Azur, Institut de Chimie de
Nice, Nice 06108 CEDEX 2, France
Christophe Marin − Expressions Parfumees, Grasse 06130,
France
(7) (a) Sim, S. H.; Lee, S. I.; Park, J. H.; Chung, Y. K. Adv. Synth. Catal.
́
2010, 352, 317. (b) Furstner, A.; Stelzer, F.; Szillat, H. J. Am. Chem. Soc.
̈
2001, 123, 11863. (c) Barreiro, E. M.; Boltukhina, E. V.; White, A. J. P.;
Hii, K. K. M. Chem. - Eur. J. 2015, 21, 2686.
Complete contact information is available at:
D
https://dx.doi.org/10.1021/acs.orglett.0c00843
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
(8) (a) Shibata, T.; Kobayashi, Y.; Maekawa, S.; Toshida, N.; Takagi,
K. Tetrahedron 2005, 61, 9018. (b) Chao, C.-M.; Beltrami, D.; Toullec,
P. Y.; Michelet, V. Chem. Commun. 2009, 6988. (c) Pradal, A.; Chao, C.-
M.; Toullec, P. Y.; Michelet, V. Beilstein J. Org. Chem. 2011, 7, 1021.
(d) Yavari, K.; Aillard, P.; Zhang, Y.; Nuter, F.; Retailleau, P.; Voituriez,
A.; Marinetti, A. Angew. Chem., Int. Ed. 2014, 53, 861. (e) Aillard, P.;
Voituriez, A.; Dova, D.; Cauteruccio, S.; Licandro, E.; Marinetti, A.
Chem. - Eur. J. 2014, 20, 12373. (f) Medena, C.; Calogero, F.; Lemoine,
Q.; Aubert, C.; Derat, E.; Fensterbank, L.; Gontard, G.; Khaled, O.;
Vanthuyne, N.; Moussa, J.; Ollivier, C.; Petit, M.; Barbazanges, M. Eur. J.
Org. Chem. 2019, 2019, 2129. (g) Guitet, M.; Zhang, P.; Marcelo, F.;
́
̀
Tugny, C.; Jimenez-Barbero, J.; Buriez, O.; Amatore, C.; Mouries-
Mansuy, V.; Goddard, J.-P.; Fensterbank, L.; Zhang, Y.; Roland, S.;
́
Menand, M.; Sollogoub, M. Angew. Chem., Int. Ed. 2013, 52, 7213.
(h) Teller, H.; Corbet, M.; Mantilli, L.; Gopakumar, G.; Goddard, R.;
Thiel, W.;Fu
Furstner, A. Chem. - Eur. J. 2011, 17, 7764. (j) Wu, Z.; Isaac, K.;
̈
rstner, A. J. Am. Chem. Soc. 2012, 134, 15331. (i) Teller, H.;
̈
Retailleau, P.; Betzer, J.-F.; Voituriez, A.; Marinetti, A. Chem. - Eur. J.
2016, 22, 3278. (k) Zhang, P.-C.; Wang, Y.; Zhang, Z.-M.; Zhang, J. Org.
Lett. 2018, 20, 7049. (l) Zuccarello, G.; Mayans, J. G.; Escofet, I.;
́
Scharnagel, D.; Kirillova, M. S.; Perez-Jimeno, A. H.; Calleja, P.; Boothe,
J. R.; Echavarren, A. M. J. Am. Chem. Soc. 2019, 141, 11858.
(9) (a) Zhang, D.-H.; Wei, Y.; Shi, M. Chem. - Eur. J. 2012, 18, 7026.
(b) Lee, S. I.; Kim, S. M.; Kim, S. Y.; Chung, Y. K. Synlett 2006, 14, 2256;
Correction: 2009, 8, 1355.
(10) For reviews, see: (a) Hopkinson, M. N.; Richter, C.; Schedler, M.;
Glorius, F. Nature 2014, 510, 485. (b) N-Heterocyclic Carbenes: From
Laboratory Curiosities to Efficient Synthetic Tools, 2nd ed.; Diez-
Gonzalez, S., Ed.; The Royal Society of Chemistry, London, 2017.
(c) Nolan, S. P. Acc. Chem. Res. 2011, 44, 91.
(11) (a) Comotti, M.; Della Pina, C.; Matarrese, R.; Rossi, M. Angew.
Chem., Int. Ed. 2004, 43, 5812. (b) Carrettin, S.; Blanco, M. C.; Corma,
A.; Hashmi, A. S. K. Adv. Synth. Catal. 2006, 348, 1283. (c) Hashmi, A.
S. K. Catal. Today 2007, 122, 211. (d) Hutchings, G. J. Top. Catal. 2008,
48, 55. (e) Marion, N.; Ramon, R. S.; Nolan, S. P. J. Am. Chem. Soc.
2009, 131, 448. (f) Oliver-Meseguer, J.; Cabrero-Antonino, J. R.;
Dominguez, I.; Leyva-Perez, A.; Corma, A. Science 2012, 338, 1452.
̈
(g) Blanco Jaimes, M. C.; Bohling, C. R. N.; Serrano-Becerra, J. M.;
Hashmi, A. S. K. Angew. Chem. 2013, 125, 8121. (h) Oonishi, Y.;
Gomez-Suarez, A.; Martin, A. R.; Nolan, S. P. Angew. Chem., Int. Ed.
2013, 52, 9767. (i) Lavallo, V.; Wright, J. H.; Tham, F. S.; Quinlivan, S.
Angew. Chem., Int. Ed. 2013, 52, 3172. (j) Blanco Jaimes, M. C.;
Rominger, F.; Pereira, M. M.; Carrilho, R. M. B.; Carabineiro, S. A. C.;
Hashmi, A. S. K. Chem. Commun. 2014, 50, 4937. (k) Wang, Y.; Wang,
Z.; Li, Y.; Wu, G.; Cao, Z.; Zhang, L. Nat. Commun. 2014, 5, 3470.
(l) Barrio, P.; Kumar, M.; Lu, Z.; Han, J.; Xu, B.; Hammond, G. B. Chem.
- Eur. J. 2016, 22, 16410. (m) Schießl, J.; Schulmeister, J.; Doppiu, A.;
Worner, E.; Rudolph, M.; Karch, R.; Hashmi, A. S. K. Adv. Synth. Catal.
2018, 360, 2493.
(12) The turnover frequencies were also high for such transformations,
respectively, 380 h−1 for 2t and 57 h−1 for 2g. The TOF was even higher
for 2g, TOF = 2300 h−1, considering that the conversion was 92% after
23 h.
(13) Sell, C. S. Angew. Chem., Int. Ed. 2006, 45, 6254.
E
https://dx.doi.org/10.1021/acs.orglett.0c00843
Org. Lett. XXXX, XXX, XXX−XXX