Organic Letters
Letter
purification, the products 3a and 3b were desilylated in
THF−H2O in the presence of a catalytic amount of HCl at 0
°C to give 4a and 4b, which were recrystallized to afford
diastereomerically pure major isomers (>99% de). Fortu-
nately, the major isomer of 4a was determined to be 3′S by
X-ray crystallography (Supporting Information). Thus, the
major isomer of 4b was correlatively assumed to be 3′R. The
major isomers of 4a and 4b could be converted into the
corresponding enantiomerically pure γ-butyrolactones (S)-5a
and (R)-5b, respectively, by treatment with a catalytic amount
of NaH in THF at 25 °C.
Table 2. Electroreductive Coupling of 2a,b with Diaryl
Ketones 1b−d and Transformation to Lactones 5c-f
Next, the electroreduction of imidazolidin-2-ones 2a,b and
oxazolidin-2-ones 2c−f with 1a was carried out under the
same conditions, and the obtained coupled products were
treated with TBAF in THF at 25 °C to give γ-butyrolactones
5a and 5b (Table 1). The sense of R2- and R3-substituents on
a
b
c
Table 1. Electroreductive Coupling of 2a−f with
Benzophenone and Transformation to Lactones 5a,b
Isolated yield. Determined by optical rotation. Not determined.
prepared from diastereomerically pure (>99% de) (3′S)-4d
and (3′R)-4f according to the same procedure as described in
Scheme 2 (Scheme 3). In addition, the stereostructures of
Scheme 3. Electroreductive Coupling of 2a,b with 1c,d and
Transformation to Enantiomerically Pure Lactones (S)-5d
and (R)-5f
a
b
run
2
R1
R2
R3
5
% yield
% ee
1
2
3
4
5
6
2a
2b
2c
2d
2e
2f
Me
Ph
Ph (S)
Ph (S)
Ph (R)
Ph (R)
i-Pr (S)
i-Pr (S)
Me (R)
(S)-5a
(R)-5b
(R)-5a
(S)-5b
(S)-5a
(R)-5b
63
60
68
47
78
40
99
93
95
99
95
59
Me (R)
Me
Ph
H
H
H
H
Me
Ph
a
b
Isolated yield. Determined by optical rotation.
the chiral auxiliaries in 2 apparently decides the sense of R1-
substituent on the products. That is, (S)-5a and (R)-5b were
selectively produced from (5S)-phenyl-(4R)-methyl-substi-
tuted 2a,b and (4S)-isopropyl-substituted 2e,f (runs 1, 2, 5,
and 6), whereas (R)-5a and (S)-5b were selectively formed
from (4R)-phenyl-substituted 2c,d (runs 3 and 4). The
reactions of the N-E-crotonoyl substrates 2a,c,e gave 5a with
good yields and high enantiomeric excesses (runs 1, 3, and 5).
Among the N-cinnamoyl-substituted substrates 2b,d,f, imida-
zolidin-2-one 2b afforded 5b with 60% yield and 93% ee (run
2), although oxazolin-2-ones 2d,f gave 5b in somewhat lower
yields (runs 4 and 6).
4,4′-Difluorobenzophenone (1b), 4,4′-dimethoxybenzophe-
none (1c), and dibenzosuberone (1d) were employed as a
diaryl ketone, and the results are summarized in Table 2.
Optically active 4,5,5-trisubstituted lactones (S)-5c,d,e and
(R)-5f were obtained by the electroreductive coupling of 2a,b
with 1b−d and following desilylation with TBAF. Although
the enantioselectivities of (S)-5c and (S)-5e could not be
determined, those of (S)-5d and (R)-5f were ascertained to
be 99% ee and 93 ee, respectively, by comparison of their
optical rotations with those of enantiomerically pure samples.
Enantiomerically pure samples of (S)-5d and (R)-5f were
(3′R)-4f and (R)-5f were confirmed by X-ray crystallography.
Unfortunately, the electroreduction of 2a with acetophenone
or cyclohexanone gave no cross-coupled products under the
same conditions.
The presumed reaction mechanism of the electroreductive
coupling of 2a with 1a is illustrated in Scheme 4. The cyclic
voltamograms of 1a in 0.03 M Bu4NClO4/DMF on a
platinum cathode showed a first reduction peak at −1.87 V
vs SCE, while those of 2a under the same conditions revealed
no reduction peak from 0 to −2.50 V vs SCE. These results
suggest that 1a is more reducible than 2a. Therefore, the
electroreductive coupling was supposed to be initiated by the
reduction of 1a. Carbanion A is formed by the two-electron
transfer to 1a and following O-silylation with TMSCl. The
B
dx.doi.org/10.1021/ol5013789 | Org. Lett. XXXX, XXX, XXX−XXX