Furthermore, these reaction conditions tolerated a wide
variety of functional groups, including methyl (3q),
methoxy (3i), cyano (3k), fluoro (3o), trifluoromethyl
[5] Z. Xiong, C. Pei, P. Xue, H. Lv, X. Zhang, Chem.
Commun. 54 (2018) 3883.
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Hussmann, J.C. Shei, B.F.J. Smith, Org. Chem. 47 (1982)
(3n), and chloro (3m, 3r).
3
(
773; (b) D. Villemin, B.A. Alloum, Synth. Commun. 20
1990) 925.
7] K. Masayuki, Y. Junya, N. Takuya, H. Yoshiro,
Tetrahedron Lett. 65 (2009) 10477.
8] T. Abeda, H. Siddiki, O. Wataru, K. Kenichi, S. Ken,
Green Chem. 18 (2016) 2554.
9] (a) B. Zheng, T.Z. Jia, P.J. Walsh, Org. Lett. 15 (2013)
690; (b) Y. Hu, Z.C. Chen, Z.G. Le, Q.G. Zheng, J. Chem.
Res. 4 (2004) 267.
10] (a) P. Maity, D.M. Shacklady, G. P. A. Yap, E.R.
Sirianni, M.P. Watson, J. Am. Chem. Soc. 135 (2013) 280;
b) D.M. Shacklady, K.M Roberts, C.H. Basch, Y.G.
Disappointingly,
enantioenriched
quaternary
ammonium salts only provided racemic products under
the optimized conditions. Fortunately, racemization was
inhibited when 1,1′-ferrocenediyl-bis(diphenylphosphine)
dppf) was added as a ligand. For example, (R)- and (S)-
-phenylethanamines from Aladdin reagent company
have enantiopurities of 94.1% and 94.6%, respectively
[
[
(
1
[
1
(
(
for HPLC traces, see the ESI), and their corresponding
S)- and (R)-benzylic sulfone products 3t have
[
enantiopurities of 92% and 91%, respectively. As a result,
all of the enantioenriched benzylic quaternary
ammonium salts which were synthesized from
commercially available enantioenriched benzylic amines
possessed high enantiopurities of 90-95% ((S)- and (R)-
(
Song, M.P. Watson, Tetrahedron 70 (2014) 4257; (c) J.
Hu, H. Sun, W. Cai, X. Pu, Y. Zhang, Z. Shi, J. Org. Chem.
8
1 (2016) 14.
11] (a) Y. Gui, S. Tian, Org. Lett. 19 (2017) 1554; (b)
3
s, 3t, 3u, 3v).
[
This reaction shows an interesting phenomenon: R
W.L. Jiang, N.T. Li, L.H. Zhou, Q.L. Zeng, ACS Catal. 8
(2018) 9899.
[12] H.Y. Chen, H. Yang, N. Li, X. Xue, Z. He, Q.L.
Zeng, Org. Proc. Res. Dev. 23 (2019) 1679.
[13] N.T. Li, F. Chen, G.H. Wang, Q.L. Zeng, Monatsch.
Chem. 151 (2019) 99.
forms of the enantioenriched benzylic amine-derived
chiral quaternary ammonium salts gave the S form of the
sulfones and vice versa. For example, the (R)-1-
phenylethylamine-derived quaternary ammonium salt
afforded (S)-3v, which was verified via comparison with
the chiral HPLC trace and specific rotation of previously
reported (S)-3v [11]. It appears that the copper-catalyzed
[14] Q.L. Zeng, L. Zhang, Y. Zhou, Chem. Rec. 18 (2018)
1278.
C-S bond coupling reaction occurs via a S
N
2 type
[15] N. Ileby, M. Kuzma, L.R. Heggvik, S.K. Fiksdahl,
Tetrahedron: Asymm. 8 (1997) 2193.
[16] R.A. Moss, J. Banger, Tetrahedron Lett. 15 (1974)
3549.
substitution, and thus the absolute configurations of the
chiral quaternary ammonium salts reverse during the C-S
bond coupling reaction.
SO2Na Cu O, DMF, K CO
3
O
S
N
2
2
+
120 oC, 24 h
OTf
a (10 mmol)
O
1
2a (20 mmol)
3
a (2.023 g, 87% yield)
Scheme 2. Gram-scale reaction.
In order to verify the scale-up possibility of this
reaction, a gram-scale reaction was performed. A ten-
mmol-scale reaction provided the corresponding product
in 87% yield (Scheme 2).
In summary, an efficient method was developed for
the synthesis of (enantioenriched) benzylic sulfones via
2
the Cu O-catalyzed C-S bond cross coupling reaction of
(enantioenriched) benzylic quaternary ammonium salts
and sodium alkane-/arene-sulfinates. Enantioenriched
sulfones were obtained in excellent enantiopurities using
dppf as a ligand.
Acknowledgments
This work was financially supported by the State Key
Laboratory
of
Geohazard
Prevention
and
Geoenvironment Protection (No. SKLGP2018Z002) for
financial support.
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