Aldehyde-catalyzed transition metal-free dehydrative β-alkylation of methyl carbinols with alcohols

Article abstract of DOI:10.1002/adsc.201200996

Different to the borrowing hydrogen strategy in which alcohols were activated by transition metal-catalyzed anaerobic dehydrogenation, the direct addition of aldehydes was found to be an effective but simpler way of alcohol activation that can lead to efficient and green aldehyde-catalyzed transition metal-free dehydrative C-alkylation of methyl carbinols with alcohols. Mechanistic studies revealed that the reaction proceeds via in situ formation of ketones by Oppenauer oxidation of the methyl carbinols by external aldehydes, aldol condensation, and Meerwein-Ponndorf-Verley (MPV)-type reduction of α,β-unsatutated ketones by substrate alcohols, affording the useful long chain alcohols and generating aldehydes and ketones as the by-products that will be recovered in the next condensation to finish the catalytic cycle. Copyright

Full text of DOI:10.1002/adsc.201200996

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DOI: 10.1002/adsc.201200996
Aldehyde-Catalyzed Transition Metal-Free Dehydrative
b-Alkylation of Methyl Carbinols with Alcohols
Qing Xu,a,* Jianhui Chen,a and Quan Liua
a
College of Chemistry and Materials Engineering, Wenzhou University, Wenzhou, Zhejiang 325035, Peopleꢀs Republic of
China
Fax : (+86)-577-8668-9300; phone: (+86)-138-577-45327; e-mail: qing-xu@wzu.edu.cn
Received: November 12, 2012; Revised: December 14, 2012; Published online: February 22, 2013
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201200996.
Abstract: Different to the borrowing hydrogen
strategy in which alcohols were activated by transi-
tion metal-catalyzed anaerobic dehydrogenation,
the direct addition of aldehydes was found to be an
effective but simpler way of alcohol activation that
can lead to efficient and green aldehyde-catalyzed
transition metal-free dehydrative C-alkylation of
methyl carbinols with alcohols. Mechanistic studies
revealed that the reaction proceeds via in situ for-
mation of ketones by Oppenauer oxidation of the
methyl carbinols by external aldehydes, aldol con-
densation, and Meerwein–Ponndorf–Verley (MPV)-
type reduction of a,b-unsatutated ketones by sub-
strate alcohols, affording the useful long chain alco-
hols and generating aldehydes and ketones as the
by-products that will be recovered in the next con-
densation to finish the catalytic cycle.
hols as the alkylating reagents [Eq. (2)].[3–6] This
method is preferable from the synthetic point of view,
because the alcohols, although less active, are much
greener chemicals than the corresponding activated
alkyl halides or carbonyl compounds,[7,8] and because
the reaction can afford the target alcohols with rela-
tively high atom efficiency by producing water as the
only by-product.
Firstly reported by Cho and co-workers with use of
RuCl2ACHTNUGRTNEUNG
(PPh3)3,[3] this reaction was later improved by
other groups by using Ru,[4] Ir,[5] or other transition
metal catalysts.[6] These reactions, currently termed as
the borrowing hydrogen or hydrogen autotransfer
methodology,[7] are believed to proceed via anaerobic
dehydrogenative alcohol activation to aldehydes, de-
hydrative condensation, and reduction of the inter-
mediates by the in situ generated hydridometal spe-
cies [Eq. (2)]. However, these methods still suffer
from the use of large amounts of hydrogen acceptors
or bases, long reaction times, or low selectivity of the
products.[3–6] Besides, using preformed noble metal
complexes or addition of capricious ligands for cata-
lyst activation are not only expensive, not readily ac-
cessible and toxic, but are also severe drawbacks of
the methods, especially in pharmaceutical, biochemi-
Keywords: alcohols; aldehyde catalysis; C-alkyla-
tion reaction; relay race mechanism; transition
metal-free conditions
À
Developing efficient methods for C C bond forma- cal, and industrial applications.
tion is a major research topic in synthetic chemistry.
While others are interested in developing catalysts
Current trends in the area have placed more and or tuning ligands by employing the borrowing hydro-
more emphasis on green catalytic methodologies such gen strategy,[3–7,9,10] we focused more on the reactions
as organocatalytic reactions that use greener catalysts, themselves and the mechanisms,[8e,11–13] and developed
cascade reactions like C H activation that can use the air-promoted metal-catalyzed aerobic N-[11] and
À
more available substrates and shorten the procedures, C-alkylation[12] methods. During our ongoing studies,
and those that can avoid the use of mutagenic and we found that the direct addition of external alde-
waste-producing reagents.[1] For example, b-C-alkyla- hydes can be a simpler way of alcohol activation,
tion of methyl carbinols for the synthesis of the useful which then leads to aldehyde-catalyzed transition
long chain alcohols, a reaction that used to be accom- metal-free dehydrative N-[14] and C-alkylation meth-
plished via tedious and wasteful multi-step processes ods for a wide range of substrates. To the best of our
[Eq. (1)],[2] has recently been realized by the transi- knowledge, aldehyde-catalyzed reactions are still very
tion metal-catalyzed one-pot tandem dehydrative C- rare up to date.[15] Herein we report in detail the effi-
alkylation of methyl carbinols by directly using alco- cient and green aldehyde-catalyzed dehydrative b-C-
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Qing Xu et al.
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alkylation reaction of methyl carbinols with alcohols (4a) as the catalyst (Table 1). Initially, only a trace of
[Eq. (3)] and propose a mechanism for the reac- product was detected in the blank reaction (run 1)
tion.[16,17]
and reactions using either KOH or 3a only;[18,19] while
The reaction was firstly optimized under solvent- addition of both 20 mol% of KOH and 3a could dra-
free conditions using commercial benzyl alcohol (1a) matically enhance the reaction rate to afford good
and 1-phenylethanol (2a) as the substrates, KOH as yield and good selectivity of the target product 5aa
the base, and benzaldehyde (3a) or acetophenone over by-product 7aa (run 2). Notably, another possi-
Table 1. Screening and optimization of the reaction conditions.[a]
Run
KOH, 3a, 4a (mol%)
atm., T, t
5+7 [%], 5/7[b]
1
2
3
4
0, 0, 0
air, 1358C, 8 h
air, 1358C, 8 h
air, 1358C, 8 h
air, 1358C, 8 h
air, 1358C, 8 h
N2, 1358C, 8 h
N2, 1208C, 12 h
30 h
N2, 1208C, 30 h
N2, 1108C, 32h
N2, 1008C, 50 h
N2, 1108C, 32 h
N2, 1108C, 32 h
trace, –
77, 89/11
93, 93/7
68, 93/7
54, –
20, 20, 0
33, 20, 0
33, 0, 20
100, 0, 0
30, 20, 0
30, 20, 0
5
6[c]
7[c]
>99, 97/3
98, 97/3
>99,>99/1
>99,>99/1
>99 (92)[e], >99/1
91,>99/1
63,>99/1
90, 97/3
8[c,d]
9[c]
30, 20, 0
30, 20, 0
30, 20, 0
30, 20, 0
30, 20, 0
10[c]
11[c,f]
12[c,g]
[a]
Unless otherwise noted, commercial 1a (3.3 mmol, 1.1 equiv) and 2a (3 mmol), absolute 3a and/or 4a, and KOH (AR
grade, >90% purity) was sealed under air or N2 in a 20-mL Schlenk tube. The mixture was then heated and monitored
1
1
by GC-MS and/or H NMR analysis. As analyzed by H NMR, commercial 1a is contaminated by <1% 3a, commercial
2a by <2% 4a.
[b]
1
Conversions of the reactions based on 2a and 5aa/7aa ratios were determined by H NMR spectroscopic analysis of the
reaction mixture.
1.3 equiv. 1a.
KOH of 99.52% purity was used.
The yield in parenthesis is isolated yield.
[c]
[d]
[e]
[f]
30 mol% 18-crown-6 (1 equiv. to 30 mol% KOH).
Virgin glassware and stirring bar, absolute 1a, 2a and 3a, and 4N grade KOH (99.99% purity) were used.[22]
[g]
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Aldehyde-Catalyzed Transition Metal-Free Dehydrative b-Alkylation of Methyl Carbinols
ble by-product and also the intermediate of the reac- (runs 9, 12, 17) and those with reactive substituents
tion, a,b-unsaturated ketone 6aa, was not detected. (runs 4, 10–15), reacted to give usually good to high
During condition screening, we found that both alde- yields of the target alcohols in good to high selectivi-
hyde and KOH are crucial for the reaction.[19] Thus, ties (runs 1–17). In some cases, since the reactions
more loadings of KOH could give higher yield and under the optimized conditions were not satisfactory
higher selectivity of the product (run 3), and aldehyde enough, they were conducted under conditions using
is a much better catalyst than 4a (run 4) or than di- slightly higher amounts of 3 and/or KOH (runs 3–5),
rectly running the reactions under air (run 5).[19,20] or at higher temperatures in longer times (runs 5, 13–
Further condition screening showed that the product 17) to improve the product yields and selectivities. As
yield and selectivity could be improved by running to heterobenzylic alcohols, the reactions were general-
the reaction under nitrogen (run 6) even at lower ly slower than those of the benzylic alcohols and thus
temperatures (runs 7–10), albeit requiring longer re- were conducted at higher temperatures to obtain sat-
action times. The reaction at 1108C (run 9) was isfactory results (runs 18–21).
chosen as the best condition for it was completed to
afford target 5aa in a high isoalted yield (92%) and secondary aliphatic alcohols; although these reactions
the highest selectivity (>99%). had to be carried out at a higher temperature of
The same method is also suitable for primary and
Since both aldehyde and base are crucial and they 1608C in longer time by using 30 mol% of 3 (runs 22–
have a synergistic effect on catalyzing the reaction, 30), possibly due to the lower reactivity of the aliphat-
this C-alkylation reaction is most possibly a transition ic alcohols. Thus, both electron-rich and electron-defi-
metal-free process.[14] Firstly, 18-crown-6, well-known cient benzylic alcohols reacted with secondary ali-
in having strong complexation ability with potassium phatic alcohols to afford moderate to good yields of
cations,[21] was added to the reaction. The results the products in high selectivities (runs 22–26). The re-
showed that it greatly retarded the reaction to give actions of primary aliphatic alcohols with electron-
only a moderate yield of the product (Table 1, run rich and electron-deficient 1-arylethanols are similar
11), confirming that potassium cation plays a dominant (runs 27–30). In similar circumstances, it was found
role in the reaction other than the unclear transition that the catalyst aldehydes were better to be added in
metal contaminants.[14] Moreover, the facts that the three portions (runs 21, 25, 28), for better results
reaction with only 1 equivalent of AR-KOH was not could be obtained in this way (see runs 27 and 28 for
effective (run 5)[19] and the reaction of 2N KOH gave comparison). The reaction of a cyclic secondary alco-
the same good result as with AR-KOH under the hol was not that satisfactory at present, giving only
same conditions (runs 7 and 8) also indicated that the a lower yield and a lower selectivity of the products
amounts of the metal contaminants in the bases (asso- at present (run 31). Moreover, secondary benzylic al-
ciated with the base purity) do not affect the reaction cohols could also be used as the alkylating reagent.
at all. This point is further supported by other proofs. Thus, under similar conditions in the presence of cata-
For example, the results of base effect screening[19] lyst 4a, 2a alone afforded good yield of the target
not only revealed that different bases vary greatly in product in good selectivity (run 32).
activities and that KOH is the best base for the reac-
As to the mechanism of the reaction, based on our
tion, but also implied that the possible metal contami- own work[11,12,14] and the literature,[16,23] and as demon-
nants in the AR grade bases do not work in the reac- strated below, the transition metal-free relay race
tion and that KOH played a much more significant mechanism (Scheme 1)[14] rather than other types of
role than those metal contaminants. In addition, to mechanisms should be the most probable one for this
exclude the possibilities of transition metal contami- aldehyde-catalyzed C-alkylation reaction.
nants-catalyzed processes, a control reaction using
Firstly, in the presence of KOH, the added alde-
virgin glassware and stirring bar, absolute 1a, 2a and hyde 3 should undergo the Meerwein–Pondorf–
3a, and 4N grade KOH (99.991% purity) was also ex- Verley–Oppenauer (MPV-O) redox reaction with the
amined under the optimized conditions (run 12) and methyl carbinols 2 to give the corresponding reduced
it gave a rather good result.[22] Therefore, the possibil- alcohol 1 and oxidized ketone 4 [Scheme 1, step (i)],
ities of transition metal-catalyzed processes due to or the added 4 react with 1 to give 2 and 3 (see
metal contamination in the bases, catalysts, and sub- Table 1, runs 9, 10). This transition metal-free MPV-O
strates can be excluded.
transfer hydrogenation step has not only been docu-
The reactions of a series of benzylic and aliphatic, mented in the literature,[23] but can also be easily con-
primary alcohols and methyl carbinols were then ex- firmed by cross-interconversion reactions of alde-
amined to extend the scope of the aldehyde-catalyzed hydes and methyl carbinols and of primary alcohols
C-alkylation method (Table 2). Firstly, under condi- and ketones.[19] Thus, as shown in Eq. (4), the reaction
tions similar to the optimized ones, both electron-rich of aldehyde 3a and secondary alcohol 2j readily oc-
and electron-deficient benzylic alcohols 1 and 1-aryl- curred to give 1a and 4j in the presence of KOH and
ACHTUNGTRENNUNG
ethanols 2, including the sterically more bulky ones vice versa.[19,24,25]
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Qing Xu et al.
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Table 2. Extension of the substrates.[a]
Run
1
Alcohols 1
Alcohols 2
5+7 [%] (5%); 5/7[b]
>99 (92);>99/1
1a
1a
1a
1a
1a
1b
1c
2a
2b
2c
2d
2e
2a
2a
2
>99 (81); 94/6
>99 (87);>99/1
>99 (80); 94/6
>99 (68); 91/9
>99 (83); 94/6
>99 (81); 94/6
3[c]
4[c]
5[c,d]
6
7
8
1d
2a
>99 (78);>99/1
9
1e
1f
1g
2a
2a
2a
>99 (74); 94/6
>99 (83);>99/1
98 (74); 96/4
10
11
12
1h
2a
78 (51); 97/3
13[e]
14[e]
1i
1j
2a
2a
60 (44); 87/13
93 (69); 95/5
15[e]
16[e]
1k
1l
2a
2a
89 (63); 91/9
>99 (79); 94/6
17[e]
1m
1n
2a
2a
>99 (75); 86/14
18[d,f]
92 (61); 87/13
19[d,f]
20[d,f]
1n
1n
2b
2d
97 (69); 84/16
44 (32); 94/6
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Aldehyde-Catalyzed Transition Metal-Free Dehydrative b-Alkylation of Methyl Carbinols
Table 2. (Continued)
Run
Alcohols 1
Alcohols 2
5+7 [%] (5%); 5/7[b]
>99 (66); 78/22
87 (59);>99/1
21[e–h]
1o
1a
2a
2f
22[d,f]
23[d,f]
24[d,f]
1b
1f
2f
2f
57 (34);>99/1
72 (45);>99/1
25[d,f,h]
1a
2g
72 (52);>99/1
26[d,f]
27[d,f]
1a
1p
2h
2a
53 (37);>99/1
72 (43);>99/1
28[d,f,h]
29[d,f]
30[d,f]
1p
1p
1p
2a
2b
2d
83 (69);>99/1
54 (41);>99/1
56 (39);>99/1
31[d,f,i]
1a
1a
2i
75 (35); 59/41
92 (64); 85/15
32[d,i,j]
2a
[a]
Unless otherwise noted, commercial alcohols 1 (3.9 mol, 1.3 equiv.) and 2 (3 mmol), corresponding aldehyde 3
(20 mol%), and KOH (30 mol%) were degassed and then sealed under nitrogen in a 20-mL Schlenk tube. The mixture
1
was then heated at 1108C for 32 h and monitored by GC-MS and/or H NMR analysis.
Unless otherwise noted, conversions of the reactions based on 2 and 5/7 ratios were determined by H NMR spectroscop-
[b]
1
ic analysis of the reaction mixture. Isolated yields of 5 based on 2 are shown in parenthesis.
1.5 equiv. 1, 30 mol% 3, 50 mol% KOH.
1608C, 72 h.
1308C, 48 h.
30 mol% 3.
3 mmol 1 and 6 mmol 2 (2 equiv.).
The aldehyde was added in 3 portions (10 mol% per portion).
Conversion and ratio of the reaction were determined by GC-MS analysis due to unidentifiable complex NMR spectra.
6 mmol 2a and 30 mol% 4a.
[c]
[d]
[e]
[f]
[g]
[h]
[i]
[j]
Secondly, once the the more reactive aldehyde 3 proven in previous studies,[3–7,10,12] and can readily
and ketone 4 are both present in the reaction, they occur at room temperature in the presence of KOH
should undergo the facile dehydrative aldol condensa- [Eq. (5)],[19] it should be a fast step in the catalytic
tion to give a,b-unsatutated ketones 6 [Scheme 1, step cycle. As a result, it can drive the interconversion re-
(ii).] Since this step is a classic organic reaction, well- actions [step (i)] forward by producing intermediate 6
as 6 will be further reduced to 7 and 5.
Finally, the transfer hydrogenative reduction of 6
by primary alcohols 1 and/or methyl carbinols 2 to
give product 5 and by-product 7 [Scheme 1, steps (iii)
and (iv)] could also be easily confirmed. As shown in
Eq. (6) (a similar condition to the reactions in
Table 1), by using 1a or 2a as the hydrogen source
and KOH as the base, 6aa could be easily reduced to
5aa and 7aa in moderate to good yields and good to
high selectivities in the absence of metal catalysts.[19]
More importantly, as shown in Eq. (7), by using
1 equivalent of phenylACTHNUTRGNEU(GN p-tolyl)methanol 2k as the re-
ducing alcohol, the ratio of the hydrogen atoms re-
ceived by 6aa to give 5aa (4 hydrogen atoms per mol-
ecule) and 7aa (2 hydrogen atoms per molecule) to
those donated by 2k to give 4k (2 hydrogen atoms per
Scheme 1. Proposed mechanism for the aldehyde-catalyzed
C-alkylation reaction of methyl carbinols with alcohols.
Adv. Synth. Catal. 2013, 355, 697 – 704
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Qing Xu et al.
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1
molecule) can be clearly analyzed by H NMR spec- base, which may in turn solve the catalyst recovery,
troscopy to be almost 1/1 [Eq. (7), run 1].[19] Similarly, reuse, deactivation, and metal leaching and residue
another reaction using 3 equivalents of 2k also reflect- problems accompanied with the metal-catalyzed
ed well the same transformation [Eq. (7), run 2]. methods. Due to the many obvious advantages, this
These results clearly indicate that the hydrogen atoms alcohol-based aldehyde-catalyzed dehydrative alkyla-
of alcohols 1 and/or 2 were quantitatively transferred tion method should potentially be of wide interest in
to intermediate 6 to give intermediate 7 and finally many fields. Further extension and deeper mechanis-
the product 5 in the transfer hydrogenation steps tic studies of the reaction are underway.
[Scheme 1, steps (iii) and (iv)], regenerating mean-
while quantitative amounts of 3 and 4 as the by-prod-
ucts, which should soon be recovered [step (v)] in the Experimental Section
next condensation step [step (ii)] to finish the catalytic
cycle. Besides, the first transfer hydrogenation step Typical Procedure for Aldehyde-Catalyzed De-
[step (iii)] should be a fast reaction and the second hydrative C-Alkylation of Methyl Carbinols with
one [step (iv)] a slower reaction in the catalytic cycle, Alcohols
since 6 was not observed and 7 was detected as the
by-product in the reaction media. On the other hand,
since no metal catalysts were used and the possibili-
The mixture of benzyl alcohol 1a (0.40 mL, 3.9 mmol,
1.3 equiv.), 1-phenylethanol 2a (0.36 mL, 3.0 mmol), KOH
(50.5 mg, 0.9 mmol, 30 mol%), and absolute benzaldehyde
ties of transition metal-catalyzed pathways have been
excluded, these transfer hydrogenation steps should
also proceed via similar MPV-O type processes.[14,16,23]
In summary, we have developed an efficient and
green aldehyde-catalyzed transition metal-free dehy-
drative C-alkylation method for preparation of the
useful long chain alcohols that can directly use vari-
ous benzylic and aliphatic, primary alcohols and
methyl carbinols as the substrates. This work demon-
strates again that addition of aldehydes is indeed an
effective protocol of alcohol activation, extending the
scope of aldehyde-catalyzed alkylation method and
the transition metal-free relay race mechanism.[14] Al-
though the aldehyde of the corresponding alcohol was
used as the catalyst, this method is still preferable
from a synthetic point of view because it requires no
expensive metal catalysts and activating ligands, but
3a (61 mL, 0.06 mmol, 20 mol%) in a 20-mL Schlenk tube
was sealed under nitrogen, and then heated at 1108C. After
completion of the reaction as was monitored by GC-MS
and/or 1H NMR (>99% yield and >99/1 selectivity by
1H NMR), the mixture was quenched with ethyl acetate,
washed successively with dilute hydrochloric acid, brine, and
water, and extracted with ethyl acetate. The combined or-
ganic layer was then dried over MgSO4 and concentrated
under vacuum. Column chromatography of the crude prod-
uct using ethyl acetate and petroleum ether (60–908C) (v/v
1/30) gave 5aa; isolated yield: 0.586 g (92%).
Acknowledgements
We thank NNSFC (No. 20902070), SRF for ROCS of SEM,
ZJNSF (No. Y4100579), ZJQJTP (No. QJD0902004), and
merely the cheap and readily available aldehydes and Xinmiao Talents Program of Zhejiang Province (No.
702
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ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 697 – 704

Aldehyde-Catalyzed Transition Metal-Free Dehydrative b-Alkylation of Methyl Carbinols
2012R424055) for financial support. We also thank S. Liao
for performing some reactions.
ziello, F. De Vincentiis, P. G. Cozzi, Eur. J. Org. Chem.
2011, 647; e) Q. Xu, Q. Li, Chin. J. Org. Chem. 2013,
33, 18, and references cited therein.
[9] For N-alkylation reactions carried out under air: a) F.
Shi, M. K. Tse, X. Cui, D. Gçrdes, D. Michalik, K.
Thurow, Y. Deng, M. Beller, Angew. Chem. 2009, 121,
6026; Angew. Chem. Int. Ed. 2009, 48, 5912; see also:
X. Cui, F. Shi, M. K. Tse, D. Gçrdes, K. Thurow, M.
Beller, Y. Deng, Adv. Synth. Catal. 2009, 351, 2949;
b) P. R. Likhar, R. Arundhathi, M. L. Kantam, P. S.
Prathima, Eur. J. Org. Chem. 2009, 5383; c) R. Kawa-
hara, ; K.-I. Fujita, R. Yamaguchi, Adv. Synth. Catal.
2011, 353, 1161; d) A. Martꢂnez-Asencio, M. Yus, D. J.
Ramꢃn, Synthesis 2011, 3730; e) H. Ohta, Y. Yuyama,
Y. Uozumi, Y. M. A. Yamada, Org. Lett. 2011, 13, 3892.
[10] For C-alkylation reactions carried out under air:
a) Y. M. A. Yamada, Y. Uozumi, Org. Lett. 2006, 8,
1375–1378; b) Y. M. A. Yamada, Y. Uozumi, Tetrahe-
dron 2007, 63, 8492; c) L. J. Allen, R. H. Crabtree,
Green Chem. 2010, 12, 1362; d) G. Tang, C.-H. Cheng,
Adv. Synth. Catal. 2011, 353, 1918.
[11] a) C. Liu, S. Liao, Q. Li, S. Feng, Q. Sun, X. Yu, Q. Xu,
J. Org. Chem. 2011, 76, 5759; b) Q. Li, S. Fan, Q. Sun,
H. Tian, X. Yu, Q. Xu, Org. Biomol. Chem. 2012, 10,
2966.
[12] S. Liao, K. Yu, Q. Li, H. Tian, Z. Zhang, X. Yu, Q. Xu,
Org. Biomol. Chem. 2012, 10, 2973.
[13] a) L. Jiang, L. Jin, H. Tian, X. Yuan, X. Yu, Q. Xu,
Chem. Commun. 2011, 47, 10833; b) H. Tian, X. Yu, Q.
Li, Q. Xu, Adv. Synth. Catal. 2012, 354, 2671.
[14] We also reported an aldehyde-catalyzed transition
metal-free dehydrative N-alkylation of amides and
amines with alcohols: Q. Xu, Q. Li, X. Zhu, J. Chen,
Adv. Synth. Catal. 2013, 355, 73–80.
References
[1] a) P. T. Anastas, J. C. Warner, Green Chemistry: Theory
and Practice, Oxford University Press, Oxford, Eng-
land; New York, 1998; b) K. Sanderson, Nature 2011,
469, 18.
´
[2] a) M. Hudlicky, Oxidations in Organic Chemistry,
American Chemical Society, Washington DC, 1990;
b) D. Caine, in: Comprehensive Organic Synthesis, Vol.
3 (Eds.: B. M. Trost, I. Fleming), Pergamon, Oxford,
U.K. , 1991, pp 1–63; c) M. Hudlicky, Reductions in Or-
ganic Chemistry, American Chemical Society, Washing-
´
ton DC, 1986.
[3] C. S. Cho, B. T. Kim, H.-S. Kim, T.-J. Kim, S. C. Shim,
Organometallics 2003, 22, 3608.
[4] For Ru-catalyzed reactions: a) R. Martꢂnez, D. J.
Ramꢃn, M. Yus, Tetrahedron 2006, 62, 8982; b) M. Vi-
ciano, M. Sanaffl, E. Peris, Organometallics 2007, 26,
6050; c) H. W. Cheung, T. Y. Lee, H. Y. Lui, C. H.
Yeung, C. P. Lau, Adv. Synth. Catal. 2008, 350, 2975;
d) D. Gnanamgari, C. H. Leung, N. D. Schley, S. T.
Hilton, R. H. Crabtree, Org. Biomol. Chem. 2008, 6,
4442; e) D. Gnanamgari, E. L. O. Sauer, N. D. Schley,
C. Butler, C. D. Incarvito, R. H. Crabtree, Organome-
tallics 2009, 28, 321; f) X. Chang, L. W. Chuan, L.
Yongxin, S. A. Pullarkat, Tetrahedron Lett. 2012, 53,
1450.
[5] For Ir-catalyzed reactions: a) K.-I. Fujita, C. Asai, T.
Yamaguchi, F. Hanasaka, R. Yamaguchi, Org. Lett.
2005, 7, 4017; b) A. P. da Costa, M. Viciano, M. Sanaffl,
S. Merino, J. Tejeda, E. Peris, B. Royo, Organometallics
2008, 27, 1305; c) C. Segarra, E. Mas-Marzµ, J. A.
Mata, E. Peris, Adv. Synth. Catal. 2011, 353, 2078; d) C.
Xu, L. Y. Goh, S. A. Pullarkat, Organometallics 2011,
30, 6499; e) X. Gong, H, Zhang, X. Li, Tetrahedron
Lett. 2011, 52, 5596; f) refs.[4d,4e]
[6] For other metal-catalyzed reactions: a) C. S. Cho, W. X.
Ren, S. C. Shim, Bull. Korean Chem. Soc. 2005, 26,
1611; b) K.-I. Shimizu, R. Sato, A. Satsuma, Angew.
Chem. 2009, 121, 4042; Angew. Chem. Int. Ed. 2009, 48,
3982; c) O. Kose, S. Saito, Org. Biomol. Chem. 2010, 8,
896; d) J. Yang, X. Liu, D.-L. Meng, H.-Y. Chen, Z.-H.
Zong, T.-T. Feng, K. Sun, Adv. Synth. Catal. 2012, 354,
328.
[7] a) A. J. A. Watson, J. M. J. Williams, Science 2010, 329,
635; b) T. D. Nixon, M. K. Whittlesey, J. M. J. Williams,
Dalton Trans. 2009, 753; c) G. E. Dobereiner, R. H.
Crabtree, Chem. Rev. 2010, 110, 681; d) G. Guillena,
D. J. Ramꢃn, M. Yus, Chem. Rev. 2010, 110, 1611;
e) K.-I. Fujita, R. Yamaguchi, Synlett 2005, 560; f) D.-
H. Lee, K.-H. Kwon, C. S. Yi, Science 2011, 333, 1613;
g) S. Bähn, S. Imm, L. Neubert, M. Zhang, H. Neu-
mann, M. Beller, ChemCatChem 2011, 3, 1853.
[15] a) N. Guimond, M. J. MacDonald, V. Lemieux, A.
Beauchemin, J. Am. Chem. Soc. 2012, 134, 16571; b) R.
Pascal, Eur. J. Org. Chem. 2005, 1813; c) M.-P. Heck,
A. Wagner, C. Mioskowski, J. Org. Chem. 1996, 61,
6486.
[16] A base-mediated reaction carried out under air without
using transition metal catalysts has been reported by
Crabtree and co-workers (ref.[10c]). The mechanistic
proposal of the reaction, although not confirmed by
direct experimental proofs and remained a hypothesis
at the time, supports the conclusions in our previous
studies (refs.[11,12,14]) and the present work.
[17] A ferrocenecarboxaldehyde-catalyzed C-alkylation re-
action recently reported by Sun and co-workers
(ref.[6d]) should also be mentioned. Differently, it was
À
proposed to proceed via an Fe H species participating
in the mechanism.
[18] Commercial alcohols 1 and 2 are usually contaminated
by trace amounts of the corresponding carbonyl com-
pounds 3 and 4. This may account for the formation of
trace products in the reactions.
[19] See the Supporting Information for details.
[20] Possibly because the conditions adopted in our work
are different to those reported by Crabtree (ref.[10c]),
different results were obtained in the aerobic reactions.
As shown in our work, the product selectivities in aero-
bic reactions are lower than those under nitrogen.
[8] a) D.-H. Lee, K.-H. Kwon, C. S. Yi, Science 2011, 333,
1613; b) S.-Y. Zhang, F.-M. Zhang, Y.-Q. Tu, Chem.
Soc. Rev. 2011, 40, 1937; c) E. Skucas, M.-Y. Ngai, V.
Komanduri, M. J. Krische, Acc. Chem. Res. 2007, 40,
1394; d) E. Emer, R. Sinisi, M. G. Capdevila, D. Petruz-
Adv. Synth. Catal. 2013, 355, 697 – 704
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
asc.wiley-vch.de
703

Qing Xu et al.
COMMUNICATIONS
[21] a) G. W. Gokel, W. M. Leevy, M. E. Weber, Chem. Rev.
2004, 104, 2723; b) J. S. Bradshaw, R. M. Izatt, Acc.
Chem. Res. 1997, 30, 338; c) H. An, J. S. Bradshaw,
R. M. Izatt, Chem. Rev. 1992, 92, 543.
[24] The reactions of 1-arylethanols or ketones were also
tested, but complex reaction mixtures were obtained.
[25] Interconversion reactions of primary alcohols and alde-
hydes and of methyl carbinols and ketones should also
exist in the reaction.[19]
.
[22] Reactions using commercial alcohols are usually better
than those using purified absolute ones, because com-
mercial alcohols usually contain trace amounts of the
corresponding carbonyl compounds, which can facili-
tate the reactions in some degree (see refs.[11,14]).
[23] a) J. S. Cha, Org. Process Res. Dev. 2006, 10, 1032; b) J.
Ekstrçm, J. Wettergren, H. Adolfsson, Adv. Synth.
Catal. 2007, 349, 1609; c) A. Ouali, J.-P. Majoral, A.-M.
Caminade, M. Taillefer, ChemCatChem 2009, 1, 504;
d) V. Polshettiwar, R. S. Varma, Green Chem. 2009, 11,
1313.
704
asc.wiley-vch.de
ꢁ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Adv. Synth. Catal. 2013, 355, 697 – 704