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Page 4 of 11 Ji et al. Chem Synth 2022;2:17 https://dx.doi.org/10.20517/cs.2022.27

Table 1. Reaction optimization a
Entry Change from the “standard conditions” Yield (%) b er c
1 none 64 96:4
2 (R)-1b instead of (R)-1a 11 71:29
3 (R)-1c instead of (R)-1a 10 13:87
4 (R)-1d instead of (R)-1a 12 65:35
5 (R)-1e instead of (R)-1a 24 12:88
6 (R)-1f instead of (R)-1a 27 71:29
7 Cs CO instead of Rb CO 51 96:4
2 3 2 3
8 K CO instead of Rb CO 3 62 95:5
2
3
2
9 Na CO instead of Rb CO 44 94:6
2 3 2 3
10 Et O instead of MTBE 66 90:10
2
11 toluene instead of MTBE trace -
12 rt instead of 0 ºC 21 88:12
a
Unless otherwise noted, the reaction was conducted with 2a (0.2 mmol), 3a (0.2 mmol), 4a (0.1 mmol), Rb CO (0.3 mmol), (R)-1a
2 3
b
c
(0.012 mmol) and Pd dba (0.004 mmol) in MTBE (2 mL) at 0 ºC for 48 h under Ar. Isolated yields. All er values were determined by SFC.
2
3

Scheme 2. The standard conditions of the catalytic asymmetric 1,1-diarylation of allylic sulfone.

Taking advantage of the optimized conditions, the reaction scope was first examined with a variety of
arylboronic acids. In general, all arylboronic acids gave the desired product in a moderate yield with
moderate to high levels of enantioselectivity [Scheme 3]. We found that the presence of methyl or fluorine
groups at the 4-position of the phenyl ring slightly affected the yield and enantioselectivity, while electron-
deficient substituents such as chlorine, ester and trifluoromethyl groups resulted in decreased yields and
enantioselectivities (5b-5f). The reaction was also found to proceed with (4-hydroxyphenyl) boronic acid,
giving the desired product 5g in 96.5:3.5 er, albeit with a yield of 27%. Following these trials, phenylboronic
acids bearing meta substituents such as methoxy and methyl groups were also applied to this reaction, and
the corresponding products were obtained with moderate yields and high enantioselectivities (5h-5i).
Interestingly, ortho-tolylboronic acid also worked well in this protocol, yielding product 5j in 62% yield and
96:4 er. A multi-substituted phenylboronic acid was applied to this system and provided product 5k with a
high level of enantioselectivity. Naphthalen-2-ylboronic acid was also a suitable coupling partner and
delivered product 5l in 53% yield with 95.5:4.5 er. It is worth noting that a series of (heter)arylboronic acids
were also examined in this reaction. In these trials, product 5m was obtained in 60% yield with 86.5:13.5 er,
while products 5n and 5o were generated in lower yields with moderate enantioselectivities (More results
about (hetero)arylboronic acids, please see SI). Following the experiments described above, the reaction
scope was examined by assessing different aryldiazonium salts (5p-5s). Changing the substituent of the
model coupling partner 3a from a methoxy to a benzyloxy group maintained high enantioselectivity and
also gave a moderate yield. It should be noted that the absolute configuration of 5p was assigned by X-ray
crystallography . It was also determined that the meta-methoxybenzene diazonium salt was compatible
[32]
with this reaction, giving product 5q with 40% yield and 95.5:4.5 er. In addition, using ethyl ether as the