Stereodivergent Synthesis of 1-Hydroxymethylpyrrolizidine Alkaloids

Article abstract of DOI:10.1021/acs.orglett.0c01375

A first stereodivergent strategy for the asymmetric synthesis of all stereoisomers of 1-hydroxymethylpyrrolizidine alkaloids is developed using an asymmetric self-Mannich reaction as a key step. An anti-selective self-Mannich reaction of methyl 4-oxobutanoate with the PMP-amine catalyzed by a chiral secondary amine is successfully optimized for the asymmetric synthesis of (+)-isoretronecanol and (-)-isoretronecanol. A syn-selective self-Mannich reaction catalyzed by proline is utilized for the asymmetric synthesis of the diastereomer, (+)-laburnine, and its enantiomer, (-)-trachelanthamidine.

Full text of DOI:10.1021/acs.orglett.0c01375

pubs.acs.org/OrgLett
Letter
Stereodivergent Synthesis of 1‑Hydroxymethylpyrrolizidine
Alkaloids
Abhijeet M. Sarkale and Chandrakumar Appayee*
Cite This: https://dx.doi.org/10.1021/acs.orglett.0c01375
Read Online
sı
*
Metrics & More
Article Recommendations
Supporting Information
ACCESS
ABSTRACT: A first stereodivergent strategy for the asymmetric synthesis
of all stereoisomers of 1-hydroxymethylpyrrolizidine alkaloids is developed
using an asymmetric self-Mannich reaction as a key step. An anti-selective
self-Mannich reaction of methyl 4-oxobutanoate with the PMP-amine
catalyzed by a chiral secondary amine is successfully optimized for the
asymmetric synthesis of (+)-isoretronecanol and (−)-isoretronecanol. A
syn-selective self-Mannich reaction catalyzed by proline is utilized for the
asymmetric synthesis of the diastereomer, (+)-laburnine, and its
enantiomer, (−)-trachelanthamidine.
he building blocks of biological systems consist of
homochiral amino acids (only L-form) and carbohydrates
(only D-form). Also, diastereomers of organic molecules are
quite frequently witnessed in natural sources. However, a few
natural products exist in either of the enantiomeric forms and
show different biological properties.1
T
Interestingly, all possible stereoisomers of 1-hydroxymethyl-
pyrrolizidine alkaloids2 (containing two chiral centers), namely,
(+)-isoretronecanol,3 (−)-isoretronecanol,4 (+)-laburnine,5
and (−)-trachelanthamidine,6 were found in the extracts of
different flowering plants in the enantiomerically pure form. The
ester derivatives of these four stereoisomers show biological
activities such as anti-inflammatory,7 anticholinergic,8 antipar-
asitic,9 and antifungal10 activities. One of the pyrrolizidine
alkaloids, (−)-trachelanthamidine, was converted into its amide
derivatives, which were found to be potent and selective 5-HT4
receptor agonists11 (Figure 1).
Figure 1. Stereodivergent pyrrolizidine alkaloids and their derivatives.
Considering their biological importance, several synthetic
methodologies for the asymmetric synthesis of 1-hydroxyme-
thylpyrrolizidine alkaloids have been reported in the literature.
Some of these alkaloids have been synthesized using a chiral pool
approach,12 chiral auxiliaries,13 and asymmetric catalysis.14
However, to the best of our knowledge, there is no report in
the literature for the stereodivergent15 synthesis of all four
stereoisomers of 1-hydroxymethylpyrrolizidine alkaloids using
common synthetic intermediates. In continuation of our
interest15f in achieving the stereodivergent synthesis of bioactive
molecules, herein we report a first stereodivergent synthetic
strategy for the asymmetric synthesis of 1-hydroxymethylpyrro-
lizidine alkaloids.
from methyl 4-oxobutanoate 5, as shown in Scheme 1.
According to the retrosynthetic plan, (+)-isoretronecanol 1
could be accessed from bicyclic lactam 2 through a reduction
process. The bicyclic lactam 2 could be obtained from lactone 3
using selective reduction of the lactam in the presence of the
lactone functionality followed by cyclization. Lactone 3 could be
Received: April 21, 2020
We envisaged an asymmetric synthesis of (+)-isoretronecanol
1, one of the 1-hydroxymethylpyrrolizidine alkaloids starting
https://dx.doi.org/10.1021/acs.orglett.0c01375
© XXXX American Chemical Society
Org. Lett. XXXX, XXX, XXX−XXX
A

Organic Letters
pubs.acs.org/OrgLett
Letter
During the reaction optimization of anti-selective self-
Mannich reaction of methyl 4-oxobutanoate 5 with PMP-
amine 6 in DMF in the presence of PhCO2H at −20 °C, catalysts
8 and 9 failed to generate a better stereoselectivity for PMP-
lactam 4 (Table 1, entries 1 and 2). Catalyst 9 in the absence of
PhCO2H gave a poor yield and diastereoselectivity (entry 3).
Catalyst 10 was also tested for the anti-selective self-Mannich
reaction to form PMP-lactam 4; however, a poor stereo-
selectivity was observed (entry 4).
Scheme 1. Retrosynthetic Plan for the Synthesis of 1-
Hydroxymethylpyrrolizidine Alkaloids
When catalyst 11 was used for the anti-selective self-Mannich
reaction in the presence of PhCO2H at −20 °C in DMF, PMP-
lactam 4 was formed in 80% yield with a 2:1 dr and 95% ee for the
major diastereomer and 94% ee for the minor diastereomer
(entry 5). Our attempts to improve the product diastereose-
lectivity through solvent screening were unsuccessful (entries 6
and 7). A decrease in the product enantioselectivity (82% ee)
was noticed when p-NO2PhCO2H was used as an acid additive
(entry 8). Increasing the reaction temperature to 0 °C led to a
lower product yield (due to the decomposition of the self-
Mannich adduct 7) and diastereoselectivity (entry 9). The anti-
selective self-Mannich reaction in the presence of catalyst 11 and
PhCO2H at −30 °C in DMF followed by reduction using
NaBH4 and cyclization using p-TSA led to PMP-lactam 4 in 82%
isolated yield with a 4:1 dr and 98% ee of the major diastereomer
(entry 10). Further lowering the reaction temperature to −50
°C was not fruitful (entry 11).
accessed by the removal of the PMP group (p-methylphenyl
group) in the PMP-lactam 4. The asymmetric synthesis of PMP-
lactam 4 was planned using an anti-selective self-Mannich
reaction of methyl 4-oxobutanoate 5 with PMP-amine 6.
Although the anti-16 and syn-selective17 cross-Mannich
reactions and the syn-selective self-Mannich reaction18 have
been studied, an anti-selective self-Mannich reaction has not
been reported so far in the literature. Therefore, we aimed to
optimize the reaction conditions for the anti-selective self-
Mannich reaction of methyl 4-oxobutanoate 5 with PMP-amine
6 to form the anti-selective self-Mannich adduct 7. Because the
anti-selective self-Mannich adduct 7 was found to be less stable
under the reaction conditions, it was reduced using NaBH4 and
cyclized using p-TSA to form PMP-lactam 4 for further
characterization (Table 1).
After the successful optimization of the anti-selective self-
Mannich reaction, we planned for the asymmetric synthesis of
(+)-isoretronecanol 1. Initially, a gram-scale synthesis of PMP-
lactam 4 using the optimized reaction conditions was achieved
in 80% isolated yield with a 4:1 dr and 98% ee (Scheme 2). The
deprotection of the PMP group in PMP-lactam 4 was achieved
a
Table 1. Reaction Optimization for the Synthesis of PMP-Lactam 4
b
c
d
entry
catalyst
solvent
temp (°C)
time (h)
yield (%)
dr
ee (%)
e
e
1
2
3
8
9
9
DMF
DMF
DMF
DMF
DMF
THF
CH3CN
DMF
DMF
DMF
DMF
−20
−20
−20
−20
−20
−20
−20
−20
0
10
24
24
24
12
24
20
10
10
15
36
78
67
20
44
80
15
49
84
31
82
58
1:1
1:1
1:1
1:1
2:1
1:1
2:1
2:1
1:1
4:1
4:1
31 (28)
44 (36)
nd
27 (2)
95 (94)
nd
nd
82 (78)
nd
98 (95)
87 (85)
f
e
4
5
6
7
10
11
11
11
11
11
11
11
e
e
g
8
9
10
11
e
e
−30
−50
a
Reactions were performed with PMP-amine (25 mg, 0.2 mmol, 1.0 equiv), aldehyde (84 μL, 0.8 mmol, 4.0 equiv), catalyst (0.02 mmol, 10 mol
b
%), and PhCO2H (12 mg, 0.1 mmol, 50 mol %) in DMF (2 mL, 0.1 M) unless otherwise mentioned. Isolated yield of 4 after column
c
d
1
chromatography. Determined by H NMR analysis of the crude reaction mixture. Determined by HPLC analysis on a chiral stationary phase.
e
f
g
Enantiomeric excess of the minor diastereomer. Without PhCO2H. p-NO2PhCO2H (17 mg, 0.1 mmol, 50 mol %) was used.
B
https://dx.doi.org/10.1021/acs.orglett.0c01375
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
using CAN (ceric ammonium nitrate) in acetonitrile/water at 0
Scheme 3. Asymmetric Synthesis of (−)-Isoretronecanol
°C to obtain lactone 3 in 73% isolated yield.
Scheme 2. Asymmetric Synthesis of (+)-Isoretronecanol
and cyclized using p-TSA to form the PMP-lactam 14 in 76%
isolated yield with a 7:1 dr and 93% ee (Scheme 4). The
Scheme 4. Asymmetric Synthesis of (+)-Laburnine
Several attempts to convert the lactone 3 directly to
(+)-isoretronecanol 1 using excess reducing agents were
unsuccessful because an in situ cyclization to form the bicyclic
lactam after the first reduction was not favored. The selective
reduction of lactam in lactone 3 using BH3·DMS (BH3·
dimethylsulfide) was also found to be inefficient because a
complex mixture of products was formed. However, a selective
reduction of lactam in lactone 3 was achieved using Me3OBF4
and NaBH4 to obtain the crude product, which was further
treated with NEt3 in MeOH for the cyclization to form a bicyclic
lactam, and the primary alcohol was protected as a benzoyl ester
using BzCl (benzoyl chloride) under basic conditions to attain
the bicyclic lactam 12 in 48% yield over three steps. The
formation of benzoyl ester was found to be crucial for the better
purification of bicyclic lactam 12 from the minor diastereomer
using silica gel column chromatography. The reduction of
bicyclic lactam 12 using BH3·DMS followed by the deprotection
of the benzoyl group using HCl in MeOH resulted in
(+)-isoretronecanol 1 in 90% yield over two steps.
After the asymmetric synthesis of (+)-isoretronecanol 1 was
accomplished, the asymmetric synthesis of the enantiomeric 1-
hydroxymethylpyrrolizidine alkaloid, (−)-isoretronecanol ent-1,
was conceived using the commercially available enantiomeric
catalyst ent-11 (Scheme 3). Following the same experimental
procedure as discussed in Scheme 2 but with the enantiomeric
catalyst ent-11, the enantiomeric PMP-lactam ent-4 was
synthesized in 77% isolated yield with a 4:1 dr and 98% ee.
Using the same experimental procedure as discussed in Scheme
2, the PMP-lactam ent-4 was converted to (−)-isoretronecanol
ent-1 via the enantiomeric intermediates ent-3 and ent-12.
After two out of four 1-hydroxymethylpyrrolizidine alkaloids
were successfully synthesized, we turned our attention toward an
asymmetric synthesis of the diastereomeric 1-hydroxymethyl-
pyrrolizidine alkaloid, (+)-laburnine 17, via a L-proline-catalyzed
syn-selective self-Mannich reaction.18
deprotection of the PMP group in the PMP-lactam 14 was
achieved using CAN to obtain the lactone 15 in 74% isolated
yield. Lactone 15 was reduced using Me3OBF4 and NaBH4 to
obtain the crude product, which was further treated with NEt3 in
MeOH for the cyclization to form a bicyclic lactam, and the
primary alcohol was protected as a benzoyl ester using BzCl to
afford the diastereomeric bicyclic lactam 16 in 53% yield over
three steps. The reduction of the bicyclic lactam 16 using BH3·
DMS followed by deprotection of the benzoyl group using HCl
in MeOH resulted in the diastereomeric 1-hydroxymethylpyr-
rolizidine alkaloid, (+)-laburnine 17, in 92% yield over two
steps.
After the asymmetric synthesis of (+)-laburnine 17, the
enantiomeric 1-hydroxymethylpyrrolizidine alkaloid, (−)-tra-
chelanthamidine, was planned using D-proline ent-13 (Scheme
5). Following the same experimental procedure as discussed in
Scheme 4 but with D-proline ent-13, the enantiomeric PMP-
lactam ent-14 was synthesized in 79% isolated yield with a 7:1 dr
and 93% ee. Using the same experimental procedure as discussed
in Scheme 4, the PMP-lactam ent-14 was converted to
(−)-trachelanthamidine ent-17 via the enantiomeric intermedi-
ates ent-15 and ent-16.
The L-proline-catalyzed syn-selective self-Mannich reaction
was reported under different reaction conditions with respect to
the substrates.18 whereas the syn-selective self-Mannich reaction
of methyl 4-oxobutanoate 5 with PMP-amine 6 catalyzed by L-
proline 13 in DMF at 0 °C was optimized to form the syn-
selective self-Mannich adduct, which was reduced using NaBH4
C
https://dx.doi.org/10.1021/acs.orglett.0c01375
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
382355, India; orcid.org/0000-0003-1165-4918;
Email: a.chandra@iitgn.ac.in
Scheme 5. Asymmetric Synthesis of (−)-Trachelanthamidine
Author
Abhijeet M. Sarkale − Discipline of Chemistry, Indian Institute of
Technology Gandhinagar, Gandhinagar, Gujarat 382355, India
Complete contact information is available at:
https://pubs.acs.org/10.1021/acs.orglett.0c01375
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors are grateful to the SERB, India for the Core
Research Grant (CRG/2018/000575) and IIT Gandhinagar for
financial support.
REFERENCES
■
(1) (a) Finefield, J. M.; Sherman, D. H.; Kreitman, M.; Williams, R. M.
Angew. Chem., Int. Ed. 2012, 51, 4802−4836. (b) Mori, K. Chirality
2011, 23, 449−462.
In summary, we have developed the first stereodivergent
strategy for the asymmetric synthesis of all four stereoisomers of
1-hydroxymethylpyrrolizidine alkaloids, namely, (+)-isoretro-
necanol 1,3 (−)-isoretronecanol ent-1,4 (+)-laburnine 17,5 and
(−)-trachelanthamidine ent-176 using the common synthetic
intermediates. The self-Mannich reaction of methyl 4-
oxobutanoate 5 with PMP-amine 6 catalyzed by chiral
secondary amine is considered as the key reaction. The
optimization of the anti-selective self-Mannich reaction of
methyl 4-oxobutanoate 5 with PMP-amine 6 is successfully
achieved. The conversion of the anti-selective self-Mannich
adduct 7 to (+)-isoretronecanol 1 is accomplished via PMP-
lactam 4, lactone 3, and bicyclic lactam 12 as the synthetic
intermediates. The asymmetric synthesis of the enantiomeric 1-
hydroxymethylpyrrolizidine alkaloid, (−)-isoretronecanol ent-1,
is also realized using enantiomeric catalyst ent-11 via the
enantiomers of these common intermediates. The asymmetric
synthesis of the other diastereomer, (+)-laburnine 17, and its
enantiomer, (−)-trachelanthamidine ent-17, is achieved using
the syn-selective self-Mannich reaction catalyzed by L-proline 13
and D-proline ent-13, respectively. Using this methodology, a
stereodivergent synthesis of 1-hydroxymethylpyrrolizidine
alkaloids is achieved in eight steps with three column
purifications (22−26% overall yield). Further applications of
the anti-selective self-Mannich reaction for the synthesis of other
bioactive natural products are currently underway in our
laboratory.
̈
(2) Schramm, S.; Kohler, N.; Rozhon, W. Molecules 2019, 24, 498.
̈
̈
̈
(3) Brandange, S.; Luning, B.; Moberg, C.; Sjostrand, E. Acta Chem.
Scand. 1972, 26, 2558−2560.
(4) Hart, N. K.; Johns, S. R.; Lamberton, J. A. Aust. J. Chem. 1968, 21,
1393−1395.
̈
(5) (a) Galinovsky, F.; Goldberger, H.; Pohm, M. Monatsh. Chem.
1949, 80, 550−554. (b) Hart, N. K.; Lamberton, J. A. Aust. J. Chem.
1966, 19, 1259−1264.
(6) (a) Tsuda, Y.; Marion, L. Can. J. Chem. 1963, 41, 1919−1923.
(b) Catalfamo, J. L.; Martin, W. B., Jr; Birecka, H. Phytochemistry 1982,
21, 2669−2675.
(7) Hoang, L. S.; Tran, M. H.; Lee, J. S.; To, D. C.; Nguyen, V. T.;
Kim, J. A.; Lee, J. H.; Woo, M. H.; Min, B. S. Chem. Pharm. Bull. 2015,
63, 481−484.
(8) Ikeda, Y.; Nonaka, H.; Furumai, T.; Igarashi, Y. J. Nat. Prod. 2005,
68, 572−573.
(9) Al-Jaber, H. I.; Mosleh, I. M.; Mallouh, A.; Abu Salim, O. M.; Abu
Zarga, M. H. J. Asian Nat. Prod. Res. 2010, 12, 814−820.
(10) Reina, M.; Gonzalez-Coloma, A.; Gutierrez, C.; Cabrera, R.;
Henriquez, J.; Villarroel, L. Phytochemistry 1997, 46, 845−853.
(11) Flynn, D. L.; Zabrowski, D. L.; Becker, D. P.; Nosal, R.; Villamil,
C. I.; Gullikson, G. W.; Moummi, C.; Yang, D. C. J. Med. Chem. 1992,
35, 1486−1489.
(12) (a) Brambilla, M.; Davies, S. G.; Fletcher, A. M.; Thomson, J. E.
Tetrahedron: Asymmetry 2014, 25, 387−403. (b) Bertrand, S.;
Hoffmann, N.; Pete, J.-P. Tetrahedron Lett. 1999, 40, 3173−3174.
(c) Tatsuta, K.; Takahashi, H.; Amemiya, Y.; Kinoshita, M. J. Am. Chem.
Soc. 1983, 105, 4096−4097. (d) Bertrand, S.; Hoffmann, N.; Pete, J.-P.
Eur. J. Org. Chem. 2000, 2000, 2227−2238. (e) Craig, D.; Hyland, C. J.
T.; Ward, S. E. Synlett 2006, 13, 2142−2144. (f) Ishibashi, H.; Uemura,
N.; Nakatani, H.; Okazaki, M.; Sato, T.; Nakamura, N.; Ikeda, M. J. Org.
Chem. 1993, 58, 2360−2368.
ASSOCIATED CONTENT
* Supporting Information
■
sı
The Supporting Information is available free of charge at
https://pubs.acs.org/doi/10.1021/acs.orglett.0c01375.
(13) (a) Robertson, J.; Stevens, K. Nat. Prod. Rep. 2017, 34, 62−89.
(b) Chogii, I.; Njardarson, J. T. Angew. Chem., Int. Ed. 2015, 54, 13706−
13710. (c) David, O.; Blot, J.; Bellec, C.; Fargeau-Bellassoued, M.-C.;
Complete experimental procedures and characterization
of new products, NMR spectra, and HPLC chromato-
grams (PDF)
FAIR data, including the primary NMR FID files, for
compounds 1, 3, 4, 12, and 14−17 (ZIP)
́
́
Haviari, G.; Celerier, J.-P.; Lhommet, G.; Gramain, J.-C.; Gardette, D. J.
Org. Chem. 1999, 64, 3122−3131. (d) Davies, S. G.; Fletcher, A. M.;
Foster, E. M.; Houlsby, I. T. T.; Roberts, P. M.; Schofield, T. M.;
Thomson, J. E. Org. Biomol. Chem. 2014, 12, 9223−9235. (e) Delaye,
́
P.-O.; Pradhan, T. K.; Lambert, E.; Vasse, J.-L.; Szymoniak, J. Eur. J.
Org. Chem. 2010, 2010, 3395−3406. (f) Brambilla, M.; Davies, S. G.;
Fletcher, A. M.; Roberts, P. M.; Thomson, J. E.; Zimmer, D.
Tetrahedron 2016, 72, 7417−7429.
(14) (a) Koley, D.; Krishna, Y.; Srinivas, K.; Khan, A. A.; Kant, R.
Angew. Chem., Int. Ed. 2014, 53, 13196−13200. (b) Han, X.; Zhong, F.;
AUTHOR INFORMATION
Corresponding Author
■
Chandrakumar Appayee − Discipline of Chemistry, Indian
Institute of Technology Gandhinagar, Gandhinagar, Gujarat
D
https://dx.doi.org/10.1021/acs.orglett.0c01375
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
pubs.acs.org/OrgLett
Letter
Wang, Y.; Lu, Y. Angew. Chem., Int. Ed. 2012, 51, 767−770. (c) Konno,
H.; Kishi, M.; Hiroya, K.; Ogasawara, K. Heterocycles 1998, 49, 33−37.
́
(15) (a) Molinaro, C.; Scott, J. P.; Shevlin, M.; Wise, C.; Menard, A.;
Gibb, A.; Junker, E. M.; Lieberman, D. J. Am. Chem. Soc. 2015, 137,
999−1006. (b) Liu, K.; Zhu, C.; Min, J.; Peng, S.; Xu, G.; Sun, J. Angew.
Chem., Int. Ed. 2015, 54, 12962−12967. (c) Miyamura, S.; Araki, M.;
Suzuki, T.; Yamaguchi, J.; Itami, K. Angew. Chem., Int. Ed. 2015, 54,
846−851. (d) Krautwald, S.; Carreira, E. M. J. Am. Chem. Soc. 2017,
139, 5627−5639. (e) Kaldre, D.; Klose, I.; Maulide, N. Science 2018,
361, 664−667. (f) Sarkale, A. M.; Maurya, V.; Giri, S.; Appayee, C. Org.
Lett. 2019, 21, 4266−4270.
(16) (a) Gianelli, C.; Sambri, L.; Carlone, A.; Bartoli, G.; Melchiorre,
́
P. Angew. Chem., Int. Ed. 2008, 47, 8700−8702. (b) Franzen, J.; Marigo,
M.; Fielenbach, D.; Wabnitz, T. C.; Kjærsgaard, A.; Jørgensen, K. A. J.
Am. Chem. Soc. 2005, 127, 18296−18304. (c) Zhang, H.; Mitsumori, S.;
Utsumi, N.; Imai, M.; Garcia-Delgado, N.; Mifsud, M.; Albertshofer, K.;
Cheong, P. H.-Y.; Houk, K. N.; Tanaka, F.; Barbas, C. F., III J. Am.
Chem. Soc. 2008, 130, 875−886. (d) Kano, T.; Yamaguchi, Y.;
Maruoka, K. Angew. Chem., Int. Ed. 2009, 48, 1838−1840.
(e) Pouliquen, M.; Blanchet, J.; Lasne, M.-C.; Rouden, J. Org. Lett.
́
2008, 10, 1029−1032. (f) Cordova, A.; Barbas, C. F., III Tetrahedron
Lett. 2002, 43, 7749−7752.
(17) (a) Hayashi, Y.; Yamazaki, T.; Kawauchi, G.; Sato, I. Org. Lett.
2018, 20, 2391−2394. (b) Yang, J. W.; Stadler, M.; List, B. Angew.
Chem., Int. Ed. 2007, 46, 609−611. (c) Fustero, S.; Jimenez, D.; Sanz-
Cervera, J. F.; Sanchez-Rosello, M.; Esteban, E.; Simon-Fuentes, A. Org.
Lett. 2005, 7, 3433−3436. (d) Lapuerta, I.; Vera, S.; Oiarbide, M.;
Palomo, C. Chem. - Eur. J. 2016, 22, 7229−7237. (e) Ting, A.; Schaus, S.
E. Eur. J. Org. Chem. 2007, 2007, 5797−5815. (f) List, B.; Pojarliev, P.;
Biller, W. T.; Martin, H. J. J. Am. Chem. Soc. 2002, 124, 827−833.
(g) List, B. J. Am. Chem. Soc. 2000, 122, 9336−9337.
́
́
́
̈
(18) (a) Hayashi, Y.; Tsuboi, W.; Ashimine, I.; Urushima, T.; Shoji,
M.; Sakai, K. Angew. Chem., Int. Ed. 2003, 42, 3677−3680. (b) Notz,
W.; Tanaka, F.; Watanabe, S.-I.; Chowdari, N. S.; Turner, J. M.;
Thayumanavan, R.; Barbas, C. F., III J. Org. Chem. 2003, 68, 9624−
̈
9634. (c) de Figueiredo, R. M.; Frohlich, R.; Christmann, M. J. Org.
Chem. 2006, 71, 4147−4154.
E
https://dx.doi.org/10.1021/acs.orglett.0c01375
Org. Lett. XXXX, XXX, XXX−XXX