Copper promoted: N -alkylation of sulfoximines with alkylboronic acid under mild conditions

Article abstract of DOI:10.1039/c7ob02234d

The copper meditated N-methylation of sulfoximines using methylboronic acid is reported. The reactions provide excellent yields in a short span of time under mild conditions. The optimized conditions were also found to be suitable for the N-alkylation of sulfoximine with different alkylboronic acids. In addition, N-methylation and cyclopropylation of the bioactive l-methionine sulfoximine derivative was demonstrated under standard reaction conditions.

Full text of DOI:10.1039/c7ob02234d

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Copper promoted N-alkylation of sulfoximines with alkylboronic
acid under mild condition
Surabhi Gupta,a Priyanka Chaudhary,a Nalluchamy Muniyappan,b Shahulhameed Sabiahb and
Jeyakumar Kandasamya*
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
www.rsc.org/
Copper meditated N-methylation of sulfoximines using
methylboronic acid is reported. The reactions provide excellent
yields in a short span of time under mild condition. The optimized
condition was also found to be suitable for the N-alkylation of
sulfoximine with different alkylboronic acids. In addition, N-
methylation and cyclopropylation of bioactive L-methionine
sulfoximine derivative was demonstrated under standard reaction
condition.
In synthetic organic chemistry, sulfoximines have been explored as
building blocks, chiral auxiliaries, organocatalysts, fluorophores,
trifluoromethylating agents as well as directing groups for C-H
activation reactions (Figure 1).1 On the other hand, sulfoximine
derivatives have also been identified as drugs and insecticides
(Figure 1).2-3 In particular, N-methylated sulfoximine motifs were
found in many bioactive compounds.4 From a synthetic perspective,
N-methylated sulfoximines are considered stable N-protected
sulfoximines in which a selective functionalization at the α-carbon
via lithiation can be performed.5 Such lithiated sulfoximines are
extensively used as precursors for the asymmetric synthesis of
various bioactive compounds.5a
Figure 1. Biologically and chemically relevant some N-functionalized
sulfoximines.
N-Methylation of sulfoximines is typically achieved using the
Eschweiler-Clarke reaction (i.e. formaldehyde/formic acid under
reflux condition) which requires longer reaction time.4c, 5b In lieu of
Scheme 1. N-alkylation of sulfoximine with alkylboronic acid.
4a
this, methyl iodide/K2CO3 or Me3OBF4/NaOH6 is also occasionally
In the series of organoboron compounds, boronic acids have
received significant attention in synthetic organic chemistry.9 These
compounds are known to be non-toxic and stable, enabling ease of
handling and storage. Copper mediated C-N bond formation
reactions with arylboronic acids have emerged as a powerful tool
for the synthesis of various bioactive compounds and natural
products.9 In this context, N-arylation of sulfoximines with
arylboronic acid was successfully demonstrated by Bolm research
group.3a
used for the N-methylation of sulfoximines. However, these
methods provide low yields owing to poor nucleophilicity of the
nitrogen atom present in sulfoximines.7 Recently, N-methylation of
sulfoximines using di-tert-butyl peroxide was demonstrated in the
presence of copper acetate.8 Nevertheless, requirement of inert
reaction condition, prolonged reaction time and moderate yield
limit the extensive use of this protocol for N-methylation reaction.
Therefore, development of an amenable route for the synthesis of
N-methylsulfoximines is an important task.
In contrast, the application of alkylboronic acids as N-alkylating
agents is less explored.[9a] Recently, few reports have demonstrated
a copper mediated Chan-Lam type N- and O-alkylation of organic
compounds with different alkylboronic acids.10 Notably, the
reaction conditions used for N-alkylation with alkylboronic acids are
a.Department of chemistry, Indian Institute of Technology (BHU), Varanasi, Uttar
Pradesh-221005; Email: jeyakumar.chy@iitbhu.ac.in
b.Department of chemistry, Pondicherry University, Pondicherry-605014
†
Electronic
DOI: 10.1039/x0xx00000x
Supplementary
Informaꢀon
(ESI)
available:
See
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quite different from the N-arylation reactions carried out with conceptually different approach for the efficient preparation of N-
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arylboronic acids.11
DOI: 10.1039/C7OB02234D
alkyl sulfoximines under mild condition (Scheme 1). For instance,
Methylboronic acid has been used as a reagent for mono- previous methods proceed through simple substitution reaction
methylation of anilines and esterification of carboxylic acids with between a nucleophile (sulfoximine) and an electrophile (alkyl
10b
different copper salts.10a,
To best of our knowledge, N- halide) while this approach discloses a reaction in which two
methylation or alkylation of sulfoximines with respective nucleophiles (i.e. sulfoximine and alkylboronic acid) undergo
alkylboronic acid is not explored. Nevertheless, development of coupling
in
the
presence
of
Cu
(II)
species.
such protocol would provide not only an alternative route, but also
Table 1. Optimization of reaction condition for N-methylation of sulfoximine using methylboronic acid.a
aReaction Condition: Sulfoximine (1.0 mmol), methylboronic acid (2.0 equiv.), base (2.4 equiv.), and copper salt were stirred in different
solvents (8 mL) at appropriate temperature. bIsolated Yield. C Condition used for the N-arylation of sulfoximine by Bolm et.al (see ref 3a)
To execute the challenge, N-methylation of S,S-methylphenyl was performed with 0.1 equiv. copper (II) acetate in methanol using
sulfoximine (1a) was studied with methylboronic acid in the 2.0 equiv. of methylboronic acid at room temperature (Table 1,
presence of copper salts in various solvents. Initially, the reaction entry 1). In fact, this is the condition employed for the N-arylation
2 | J. Name., 2012, 00, 1-3
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of sulfoximines with arylboronic acids by Bolm et.al.3a However, no delight, under this condition, N-methyl S,S-methylphenyl
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DOI: 10.1039/C7OB02234D
reaction was detected under this condition after 12h. In addition, sulfoximine (2a) was obtained in 94% yield within 30 mins.
no reaction takes place with an equimolar amount of copper (II)
Further, the optimization of reaction condition was continued with
acetate with or without base (i.e. pyridine, 2.4 equiv.) at room
different copper (I) and copper (II) salts in the presence of pyridine
temperature as well as under reflux condition (i.e. 80 oC) in
methanol (Table 1, entries 2 and 3). Thus, the reactions were
carried out in different aprotic solvents such as THF, acetonitrile,
dichloroethane and 1,4-dioxane with one equivalent of copper (II)
acetate and pyridine at 80 0C (Table 1, entries 4-7). We were
pleased to see a significant conversion of sulfoximine 1a to the
desired N-methylated sulfoximine 2a (i.e. 86%) in 1,4-dioxane
(Table 1, entry 7), while low yields were obtained with other
solvents after 12h. Encouraged, we further modified the reaction
condition where the reaction was carried out with 1.5 equiv. of
copper (II) acetate at 100oC in 1,4-dioxane (Table 1, entry 8). To our
in 1,4-dioxane at 100 oC (Table 1, entries 9-14). Surprisingly, most of
the copper salts failed to provide significant amount of desired
product while copper (I) acetate showed a comparable reactivity to
that of copper (II) acetate (Table 1, entry 12). Furthermore, the
reactions were carried out with different organic and inorganic
bases in the presence of copper (II) acetate (Table 1, entries 15-18).
The reactions with Et3N and 4-DMAP provided good yields whereas
negligible yield was observed in the case of K2CO3 and NaOH. In
fact, 4-DMAP showed an equal reactivity to that of pyridine in the
N-methylation reaction (Table 1, entry 16).
Table 2. N-Methylation of various sulfoximines with methylboronicacid under optimized conditions.a,b
aReaction Condition: Sulfoximine (1 mmol), alkylboronic acid (2.0 equiv.), Cu(OAc)2 (1.5 equiv.), and Pyridine (2.4 equiv.) was refluxed in
1,4-dioxane (8 mL) at 100 oC in a pressure tube. bIsolated yield.
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(3e) in 95% yield within 45 mins. Similarly, DNO-cI:y1c0lo.1h0e3x9y/Cls7uOlfBo0x2im23i4nDe
With optimized condition in hand, N-methylation of various
sulfoximines was performed using methylboronic acid in the
presence of copper (II) acetate and the results are summarized in
Table 2. S,S-alkylphenylsulfoximines bearing linear or branched alkyl
chains were N-methylated successfully in excellent yields under the
optimized condition (Table 2, 2b-2e). It is noteworthy that the
sterically hindered S,S-phenyl iso-propyl sulfoximine was also
methylated in 91% yield within 60 mins (Table 2, 2d). In the case of
S,S-heptylphenyl sulfoximine, a long alkyl substituent led to slightly
longer reaction time to yield N-methylated sulfoximine 2e in 82%
yield. The substrates with electron donating or withdrawing
substituents on the phenyl ring also underwent N-methylation in
89-94% yields (Table 2, 2f-2i). In general, we observed that the
electron withdrawing group substituted phenyl sulfoximines (e.g. p-
NO2, p-Br, p-Cl) required slightly longer time for N-methylation
when compared with electron donating group substituted
sulfoximines (e.g. p-Me). In order to demonstrate the versatility of
the current methodology, N-methylation of various functionalised
3f was obtained in 91% yield.
Table 3. N-Alkylation of S,S-ethylphenyl sulfoximine (1b) with
different alkylboronic acids.a,b
O
O
NH
N
R
R
B(OH)2
S
S
Cu(OAc)2, Pyridine
Et
Et
Dioxane
Reflux
1b
3a-3f
O
O
S
S
CH3
N
CH3
N
Et
Et
3b
3a
30 mins, 90%
60 mins, 91%
O
O
S
S
Ph
N
Et
CH3
N
Et
S,S-arylalkyl, S,S-arylbenzyl
and S,S-diaryl sulfoximines were
performed under optimized condition (Table 2,2j-2q). All these
substrates were successfully N-methylated in 82-95% yield with
methylboronic acid in a short span of time. Further, N-methylation
of heterocylic sulfoximine (i.e. S,S-ethylpyridyl sulfoximine) was also
accomplished in excellent yield in 90 mins (Table 2, 2r). Similar to
3c
3d
45 mins, 91%
45 mins, 94%
O
O
S
S
N
Et
N
Et
arylsulfoximines, S,S-dibenzyl and
S,S-dialkyl sulfoximines
underwent N-methylation in high yields (Table 2, 2s and 2t), which
3e
3f
shows the versatility and broad scope of the current methodology.
40 mins, 95%
90 mins, 91%
Similar to N-methylated sulfoximines, other N-alkylated
sulfoximines also play an important role in chemistry and biology.4
However, only limited methods are available for the introduction of
alkyl groups in sulfoximines.7,12 Due to poor nucleophilicity of
aReaction Condition: Sulfoximine (1 mmol), alkylboronic acid (2.0
equiv.), Cu(OAc)2 (1.5 equiv.), and Pyridine (2.4 equiv.) was refluxed
in 1,4-dioxane (8 mL) at 100 oC. bIsolated yield.
sulfoximines, N-alkylation requires strong bases like alkali metal
hydrides or n-butyl lithium.7,
12a, 12b
Alternatively, a two-step
protocol is required, i.e. N-acylation followed by reduction, to
achieve N-alkylated sulfoximines.12c Recently, Bolm et. al. have
successfully demonstrated N-alkylation of various sulfoximines
using alkylhalides with KOH in DMSO.12d
Favourable results in N-methylation of sulfoximines with
methylboronic acid have spurred us to further explore the N-
alkylation of sulfoximines with different alkylboronic acids. Initially,
N-ethylation of S,S-ethylphenylsulfoximine (1b) with ethylboronic
acid was examined under optimized condition. To our surprise, the
reaction proceeds smoothly with similar efficiency to that of N-
methylation and gave the desired product 3a in 90% yield.
Encouraged, we further tested N-propylation, butylation and
phenethylation of sulfoximine 1b with respective boronic acids.
These reactions gave the desired N-alkylated products in excellent
yields (Table 3, 3b-3d) within 60 mins.
Scheme 2. N-Alkylation of L-methionine sulfoximine derivative
under optimized reaction condition.
L-Methionine sulfoximine is a bioactive molecule which inhibits
glutamine synthetase and g-glutamylcysteine synthetase.14 In this
respect, L-methionine sulfoximine shows considerable therapeutic
applications in animal models for many human diseases.14a To
expand the scope of our methodology, N-methylation and
cyclopropylation of bioactive L-methionine sulfoximine derivative 4
was tested with corresponding alkylboronic acids. To our delight,
the optimized reaction condition was well suited to the task and
gave N-methylated and cyclopropylated L-methionine sulfoximine
derivatives in 89-91% yield. It is remarkable that Boc-protected
The cyclopropyl group, which appears frequently in preclinical and
clinical drug molecules, has received significant attention in
medicinal chemistry due to its unique structural properties.13 Thus,
we have examined the N-cyclopropylation of sulfoximine 1b with
cyclopropylboronic acid under optimized condition. Interestingly,
the reaction provides the N-cyclopropyl S,S- ethylphenylsulfoximine
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primary amine was found to be intact during the N-methylation of
Germany for financial support through Indo-Max Planck partner
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DOI: 10.1039/C7OB02234D
group project. S. G and P. C acknowledge IIT (BHU) for a research
L-methionine sulfoximine with methylboronic acid.
fellowship. J. K thanks to Dr K. Murugan and Mr. Albert Pape for a
Finally,
a synthetic application of N-methyl sulfoximine was
helpful discussion during the manuscript preparation. J.
K
demonstrated as shown in Scheme 3. Selective lithiation of S-
methyl group in N,S-dimethyl S-phenyl sulfoximine (2a) was
performed using n-butyl lithium in dry THF, which was subsequently
reacted with benzyl bromide to obtain N-methyl S-phenyl S-(2-
phenylethyl) sulfoximine (5a) in 86% yield.
acknowledges Central Instrumentation Facility Center (CIFC)-IIT
BHU for the NMR facilities. S.S and N. M acknowledge Pondicherry
University for MASS facilities.
References and notes
1. (a) M. Reggelin and C. Zur, Synthesis, 2000, 1-64; (b) W. R.
Dong, K. Parthasarathy, Y. Cheng, F. F. Pan and C. Bolm, Chem-
Eur. J., 2014, 20, 15732-15736; (c) K. Ghosh, R. K. Rit, E.
Ramesh and A. K. Sahoo, Angew. Chem. Int. Ed., 2016, 55,
7821-7825; (d) K. Raghuvanshi, D. Zell and L. Ackermann, Org.
Lett., 2017, 19, 1278-1281; (e) V. Bizet, R. Kowalczyk and C.
Bolm, Chem. Soc. Rev., 2014, 43, 2426-2438; (f) M. Frings, I.
Thome and C. Bolm, Beilstein J. Org. Chem., 2012, 8, 1443-
1451; (g) C. Bolm, in Asymmetric Synthesis with Chemical and
Biological Methods (Eds.: D. Enders and K.-E. Jaeger), WILEY-
VCH Verlag GmbH & Co. KGaA, Weinheim, 2007, pp. 149-170;
(h) S. Noritake, N. Shibata, S. Nakamura, T. Toru and M. Shiro,
Eur. J. Org. Chem., 2008, 3465–3468.
Scheme 3. A selective functionalization of N-methyl sulfoximine via
lithiation.
A proposed mechanism for the N-methylation of sulfoximine is
shown in Scheme 4.9 In the first step, sulfoximine undergoes ligand
exchange reaction with copper (II) acetate to form intermediate A.
Further, methylboronic acid undergoes transmetallation with
intermediate
A to form intermediate B, which subsequently
2. U. Lucking, Angew. Chem. Int. Ed., 2013, 52, 9399-9408.
3. (a) C. Moessner and C. Bolm, Org Lett., 2005, 7, 2667-2669; (b)
C. A. Dannenberg, L. Fritze, F. Krauskopf and C. Bolm, Org.
Biomol. Chem., 2017, 15, 1086-1090; (c) F. Teng, J. Cheng and
C. Bolm, Org. Lett., 2015, 17, 3166-3169; (d) L. Wang, H.
Huang, D. L. Priebbenow, F.-F. Pan and C. Bolm, Angew. Chem.
Int. Ed., 2013, 52, 3478–3480; (e) F. Teng, J. T. Yu, Y. Jiang, H. T.
Yang and J. Cheng, Chem. Commun., 2014, 50, 8412-8415; (f) P.
J. Harvison and T. I. Kalman, J. Med.Chem., 1992, 35, 1227-
1233; (g) H. Zhu, J. T. Yu and J. Cheng, Chem. Commun., 2016,
52, 11908-11911; (h) C. Pimpasri, L. Sumunnee and S. Yotphan,
Org. Biomol. Chem., 2017, 15, 4320-4327; (i) F. Teng, S. Sun, Y.
Jiang and J. T. Yu, J. Cheng, Chem. Commun., 2015, 51, 5902-
5905
undergoes reductive elimination to yield the desired products.
During the reductive elimination process, Cu(II) species is converted
to Cu(0) which is basically inactive for the coupling reaction, hence
stoichiometric amount of Cu(OAc)2 is required for completion of the
reaction.
4. (a) F. W. Goldberg, J. G. Kettle, J. Xiong and D. G. Lin,
Tetrahedron, 2014, 70, 6613-6622; (b) D. P. Walker, M. P.
Zawistoski, M. A. McGlynn, J. C. Li, D. W. Kung, P. C. Bonnette,
A. Baumann, L. Buckbinder, J. A. Houser, J. Boer, A. Mistry, S.
Han, L. Xing and A. Guzman-Perez, Bioorg. Med. Chem. Lett.,
2009, 19, 3253-3258. (c) M. Frings, C. Bolm, A. Blum and C.
Gnamm, Eur. J. Med. Chem., 2017, 126, 225-245.
Scheme 4. Proposed mechanism for N-methylation reaction.
In summary, we have established a copper mediated N-methylation
of sulfoximines using methylboronic acid under mild condition. The
reaction proceeds smoothly to provide the desired products in
excellent yields in a short span of time. In addition to N-
methylation, N-alkylation of sulfoximine with different alkylboronic
acids was demonstrated. Under optimized condition, N-methylation
and cyclopropylation of bioactive L-methionine sulfoximine
derivative was achieved in high yields.
5. (a) H.-J. Gais, in Asymmetric Synthesis with Chemical and
Biological Methods (Eds.: D. Enders and K.-E. Jaeger), WILEY-
VCH Verlag GmbH & Co. KGaA, Weinheim, 2007, pp. 75-111;
(b) F. Lemasson, H. J. Gais, J. Runsink and G. Raabe, Eur. J. Org.
Chem., 2010, 2157-2175; (c) P. Lamers, D. L. Priebbenow and C.
Bolm, Eur. J. Org. Chem., 2015, 5594-5602.
6. (a) M. L.Boys, E. W.Collington, HarryFinch, S. Swanson and J.
F.Whitehead, Tetrahedron Lett., 1988, 29, 3365-3368; (b) G. K.
S. Prakash, Z. Zhang, F. Wang, C. F. Ni and G. A. Olah, J. Fluorine
Chem., 2011, 132, 792-798.
Acknowledgements
J. K. gratefully acknowledges DST-SERB India for young scientist
start-up research grant (YSS/2014/000236). J. K. also acknowledges
DST-India (DST/INT/MPG/P-09/2016) and Max-Planck Society-
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7. C. R. Johnson, C. W. Schroeck and J. R. Shanklin, J. Am. Chem.
Soc., 1973, 95, 7424–7431.
View Article Online
DOI: 10.1039/C7OB02234D
8. F. Teng, J. Cheng and J. T. Yu, Org. Biomol. Chem., 2015, 13,
9934-9937.
9. (a) D. G. Hall, Boronic Acids: Preparation and Applications in
Organic Synthesis, Medicine and Materials (Volume 1 and 2),
Second Edition ed., Wiley-VCH Verlag GmbH & Co. KGaA, 2011;
(b) E. Fernández and A. Whiting, Synthesis and Application of
Organoboron Compounds, Vol. 2015, Springer, New York,
2015.
10. (a) I. Gonzalez, J. Mosquera, C. Guerrero, R. Rodriguez and J.
Cruces, Org. Lett., 2009, 11, 1677-1680; (b) C. E. Jacobson, N.
Martinez-Munoz and D. J. Gorin, J. Org. Chem., 2015, 80, 7305-
7310; (c) R. Yamashita, A. Sakakura and K. Ishihara, Org. Lett.,
2013, 15, 3654-3657; (d) S. Benard, L. Neuville and J. P. Zhu,
Chem Commun., 2010, 46, 3393-3395; (e) L. M. Mori-Quiroz, K.
W. Shimkin, S. Rezazadeh, R. A. Kozlowski and D. A. Watson,
Chem-Eur. J., 2016, 22, 15654-15658; (f) S. A. Rossi, K. W.
Shimkin, Q. Xu, L. M. Mori-Quiroz and D. A. Watson, Org. Lett.,
2013, 15, 2314-2317; (g) T. Tsuritani, N. A. Strotman, Y.
Yaimamoto, M. Kawasaki, N. Yasuda and T. Maset, Org. Lett.,
2008, 10, 1653-1655; (h) M. Larrosa, C. Guerrero, R. Rodriguez
and J. Cruces, Synlett, 2010, 2101-2105; (i) S. Sueki and Y.
Kuninobu, Org. Lett., 2013, 15, 1544-1547.
11. In general, N-arylation reactions with arylboronic acid require
catalytic amount of copper salts in the absence of any base.
Reaction also proceeds at room temperature in methanol (See
ref 3a). On the other hand, N-alkylation reaction with
alkylboronic acid requires equivalent amount of copper salts
with base or ligands (see ref. 10a). Reaction proceeds only in
aprotic solvents at high temperature.
12. (a) C. R. Johnson and O. M. Lavergne, J. Org. Chem., 1993, 58,
1922-1923; (b) T. R. Williams and D. J. Cram, J. Org. Chem.,
1973, 38, 20-26; (c) C. Bolm, C. P. R. Hackenberger, O. Simic, M.
Verrucci, D. Muller and F. Bienewald, Synthesis, 2002, 879-887;
(d) C. M. M. Hendriks, R. A. Bohmann, M. Bohlem and C. Bolm,
Adv. Synth. Catal., 2014, 356, 1847-1852.
13. T. T. Talele, J. Med. Chem., 2016, 59, 8712-8756.
14. (a) W. S. A. Brusilow and T. J. Peters, Expert. Opin. Ther. Tar.,
2017, 21, 461-469; (b) L. Buglioni, V. Bizet and C. Bolm, Adv.
Synth. Catal., 2014, 356, 2209-2213.
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