Highly regioselective iridium-catalyzed and samarium-promoted coupling of allylic carbonates with ketones: A new approach towards homoallylic alcohols

Article abstract of DOI:10.1039/c3ra43199a

A highly regioselective Ir-catalyzed and Sm-promoted coupling of allylic carbonates with ketones has been realized, which provides the homoallylic alcohols in up to 89% yields. This strategy gives a convenient method for the synthesis of liquid crystals with a mono-fluorinated quaternary carbon chain. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3ra43199a

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Highly regioselective iridium-catalyzed and samarium-
promoted coupling of allylic carbonates with ketones:
a new approach towards homoallylic alcohols†
Cite this: RSC Adv., 2013, 3, 19917
Received 25th June 2013
*
Wei Liu, Liang Zhang, Weikang Yang and Xiaoming Zhao
Accepted 30th August 2013
DOI: 10.1039/c3ra43199a
www.rsc.org/advances
A highly regioselective Ir-catalyzed and Sm-promoted coupling of we carried out this coupling reaction in the presence of
allylic carbonates with ketones has been realized, which provides the [Ir(COD)Cl]2 (2 mol%) in tetrahydrofuran (THF) at room
homoallylic alcohols in up to 89% yields. This strategy gives a temperature under argon, no coupling product was observed
convenient method for the synthesis of liquid crystals with a mono- (entry 1). When SmI2 (2 equiv.) was added as a reducing reagent,
fluorinated quaternary carbon chain.
the formation of the homoallylic alcohol 3a and the branched
allylic alcohol 4a, with the ratio of 3a/4a being 99/1, was unex-
pectedly observed (entry 2). Such high regioselectivity with
respect to the linear allylic product is not in agreement with
what is seen in Ir-catalyzed and SnCl2-mediated carbonyl ally-
lations. In contrast, the same allylation reaction with a Pd–Sm
catalyst system gave the corresponding allylic products (3a + 4a)
with low regioselectivity (3a/4a ¼ 2.44/1).6a When (E)-cinnamyl
methyl carbonate 1b was used in place of (E)-cinnamyl acetate
1a, the yield of 3a was improved from 68% to 75% (entry 2 vs.
entry 3). Increasing the amount of SmI2 in this reaction to 2.5
equiv. produced 3a in a superior yield of 83% (entry 4).
Screening a diverse range of solvents such as THF, dime-
thoxyethane (DME), MeCN, dichloromethane (DCM), and
toluene showed THF to be the optimum solvent choice, while
other solvents such as MeCN and DME resulted in poor results
(entries 6 and 7). DCM and toluene were also both ineffective in
this reaction, presumably due to the poor solubility of SmI2
(entries 8 and 9). Changing the reaction temperature revealed
that although the reaction proceeded smoothly at room
temperature, good yields were also obtained at 10 ꢀC and 40 ꢀC
(entries 4, 10 and 11). SnCl2 (ref. 3a) was also examined as a
reducing agent and it failed to promote this coupling reaction
(entry 12). It is noteworthy that the formation of 4a was
successfully suppressed in the course of this reaction. There-
fore, the conditions presented in entry 4 of Table 1 were chosen
for further experimentation. Under the optimized conditions,
the [Ir(COD)Cl]2–SmI2 catalytic system was used to explore the
scope of the coupling of various allylic carbonates with cyclic or
acyclic ketones (Table 2). For example, either cyclohexanone 2a
or acetone 2b reacted with the allylic carbonates 1a–e to
produce the tertiary homoallylic alcohols 3a–j in moderate to
high yields (Table 2, entries 1–10). Varying the substituents on
the phenyl ring of the allylic carbonates 1a–e had a great
The iridium (Ir)-catalyzed allylation reaction has become an
important synthetic approach in organic synthesis during the
last decade, regioselectively providing branched allylic prod-
ucts.1 In this reaction, allylic carbonate or acetate can be
employed as an allyl electrophile and combined with an iridium
catalyst to form a (p-allyl)–iridium complex, which can be
rendered nucleophilic by means of an umpolung process.2 The
umpolung of the allylic fragment can be induced by reduction
with a salt (SnCl2)3 or alcoholic reductant.4 Samarium diiodide
(SmI2) serves as a one-electron reductant5 and has been utilized
in palladium (Pd)-catalyzed coupling of carbonyl compounds
with allylic acetates.6 To date, an Ir-catalyzed and Sm-promoted
allylation of carbonyl compounds with allylic carbonates has
not been reported. This method may afford both branched
allylic alcohols and homoallylic alcohols, in which a hydroxyl
group (OH) is an equivalent of a uorine atom. These tertiary
homoallylic alcohols can undergo a uorination with dieth-
ylaminosulfur triuoride (DAST) to produce the corresponding
products with a mono-uorinated quaternary carbon. Here, we
present the rst example of the Ir-catalyzed and Sm-promoted
coupling of allylic carbonates with ketones, which regiose-
lectively gives the homoallylic alcohols.
At the outset, our efforts were focused on the investigation of
an Ir-catalyzed and Sm-promoted coupling reaction between
(E)-cinnamyl acetate 1a and cyclohexanone 2a. Initially, when
Department of Chemistry, State Key Laboratory of Pollution Control and Resource
Reuse, Tongji University, 1239 Siping Road, Shanghai 200092, P. R. China. E-mail:
xmzhao08@mail.tongji.edu.cn; Fax: +86-21-65981376
† Electronic supplementary information (ESI) available. See DOI:
10.1039/c3ra43199a
This journal is ª The Royal Society of Chemistry 2013
RSC Adv., 2013, 3, 19917–19919 | 19917

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Table 2 Ir-catalyzed and Sm-promoted coupling of allylic carbonates with
inuence on the coupling reactions. (E)-Cinnamyl methyl
carbonate 1b and the allylic carbonates 1c–e with electron-
donating groups (e.g., m-MeO, p-Me, p-MeO) on the phenyl ring
gave the corresponding products in good to high yields (entries
1–3 and 6–8). In the case of the allylic carbonate 1e with an
electron-withdrawing group (e.g., o-Cl) on the phenyl ring,
3 equiv. of SmI2 and a longer reaction time were required, and
this gave only a 50% yield of 3d (entry 4). The bulky aryl (e.g.,
biphenyl and naphthyl)-substituted allylic carbonates 1h and 1f
gave 3e, 3i and 3j in moderate yields (entries 5, 9 and 10).
Notably, the formation of 4a–j was suppressed in all cases
(entries 1–10).
In contrast, the Grignard reagent (E)-cinnamylmagnesium
chloride10 reacted with 2a in THF at room temperature to afford
the corresponding product 3a in a 46% yield; 4a was not
observed in this case. A representative example of the synthetic
utility of this method is illustrated in Scheme 1. Hydrogenation
of 3e or 3j, followed by uorination with diethylaminosulfur
triuoride (DAST)7 gave the mono-uorinated compounds 3eb
or 3jb in a two-step 74% and 53% yield, respectively. Compound
3jb may exhibit good liquid crystalline properties in compar-
ketonesa
Entry
R1
R2
3/4
Product
Yieldb (%)
1
2
Ph
1b
1c
1d
1e
1f
1b
1d
1g
1h
1f
–(CH2)5–
–(CH2)5–
–(CH2)5–
–(CH2)5–
–(CH2)5–
CH3
CH3
CH3
CH3
CH3
99/1
99/1
99/1
99/1
99/1
99/1
99/1
99/1
99/1
99/1
3a
3b
3c
3d
3e
3f
3g
3h
3i
83
76
72
50
49
89
78
75
54
43
3-MeOC6H4
4-MeC6H4
2-ClC6H4
4-PhC6H4
Ph
4-MeC6H4
4-MeOC6H4
1-Naphthyl
4-PhC6H4
3
4c
5c
6
7
8
9c
10c
3j
a
Reaction conditions: 1b–f (0.2 mmol, 1.0 equiv.), 2a (0.3 mmol,
1.5 equiv.) or 2b (0.4 mmol, 2.0 equiv.), SmI2 (2.5 equiv., 5 mL, 0.1 M
in THF), and [Ir(COD)Cl]2 (2 mol%) in THF (2 mL) under argon.
b
Isolated yield. c 3.0 equiv. of SmI2, 10 h.
ison with
a known liquid crystal, 4-(4,4-dimethylpentyl)-
1,10-biphenyl.8 The introduction of uorine enhances the dipole
moment and reduces the viscosity of the liquid crystal, thereby
improving its performance.9
regioselectively provides the tertiary homoallylic alcohols in
moderate to high yields. This method can be applied to the
synthesis of liquid crystals containing a mono-uorinated
quaternary carbon chain.
Conclusions
We have developed a practical method for the synthesis of
tertiary homoallylic alcohols via Ir-catalyzed and Sm-promoted
coupling of allylic carbonates with ketones, which
Acknowledgements
We gratefully acknowledge the NSFC (21272175 and 20942003)
for generous nancial support.
Table 1 Optimization of the reaction conditions for an Ir-catalyzed and Sm-
promoted coupling of (E)-cinnamyl acetate 1a with cyclohexanone 2aa
Notes and references
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Entry
MX2 (eq.)
R
Solvent
(ꢀC)
3a/4a
Yieldb (%)
1
2
3
4
5
6
7
8
—
Ac
Ac
THF
THF
THF
THF
25
25
25
25
25
25
25
25
25
10
40
25
—
N.R.c
68
75
83
79
SmI2 (2.0)
SmI2 (2.0)
SmI2 (2.5)
SmI2 (3.0)
SmI2 (2.5)
SmI2 (2.5)
SmI2 (2.5)
SmI2 (2.5)
SmI2 (2.5)
SmI2 (2.5)
SnCl2 (2.5)
99/1
99/1
99/1
—
—
—
—
—
99/1
99/1
—
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
CO2Me
THF
DME
MeCN
DCM
Toluene
THF
10
Trace
N.R.
N.R.
78
70
N.R.
9
10
11
12
THF
THF
a
Reagents and conditions: 1a and 1b (0.2 mmol, 1.0 equiv.), 2a
(0.3 mmol, 1.5 equiv.), [Ir(COD)Cl]2 (2 mol%), SmI2 (2–3 mol%, 0.1 M
b
c
Scheme 1 Synthesis of a liquid crystal with a mono-fluorinated quaternary
in THF) in solvent (2 mL) under argon. Isolated yield. N.R. ¼ no
reaction.
carbon chain.
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RSC Adv., 2013, 3, 19917–19919 | 19919