Organoborane-Catalyzed Hydrogenation of Unactivated Aldehydes with a Hantzsch Ester as a Synthetic NAD(P)H Analogue

Article abstract of DOI:10.1055/s-0034-1378846

We have developed a method for the hydrogenation of unactivated aldehydes, using a Hantzsch ester as a NAD(P)H analogue in the presence of an electron-deficient triarylborane as a Lewis acid catalyst. Thus, tris[3,5-bis(trifluoromethyl)phenyl]borane efficiently catalyzes the hydrogenation of aliphatic aldehydes with a Hantzsch ester in 1,4-dioxane at 100 °C to give the corresponding aliphatic primary alcohols in up to 97% yield. Aromatic aldehydes also undergo the hydrogenation, even at 25 °C, to furnish the corresponding aromatic primary alcohols in up to 100% yield.

Full text of DOI:10.1055/s-0034-1378846

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© Georg Thieme Verlag Stuttgart · New York
2015, 26, 2037–2041
letter
2037
G. Hamasaka et al.
Letter
Synlett
Organoborane-Catalyzed Hydrogenation of Unactivated Alde-
hydes with a Hantzsch Ester as a Synthetic NAD(P)H Analogue
Go Hamasakaa,b
Hiroaki Tsujia,b
F3C
CF3
O
O
H
H
Yasuhiro Uozumi*a,b,c
B cat.
(5 mol%)
O
OH
EtO
OEt
+
F3C
B
CF3
R
H
1,4-dioxane
25 or 100 °C
a Institute for Molecular Science, 5-1 Higashiyama, Myodaiji,
Okazaki 444-8787, Japan
R
H
N
H
H
R = alkyl, 9 examples
up to 97% yield
R = aryl, 24 examples
up to 100% yield
R = alkyl, aryl
NAD(P)H analogue
b SOKENDAI, 5-1 Higashiyama, Myodaiji, Okazaki, 444-8787,
Japan
CF3
CF3
c Green Nanocatalysis Research Team, RIKEN Center for
Sustainable Resource Science, Hirosawa, Wako, 351-0198,
Japan
B cat.
Received: 03.06.2015
Accepted after revision: 11.06.2015
Published online: 23.06.2015
motes the hydrogenation of acetaldehyde with NADH un-
der anaerobic conditions to give ethanol (Scheme 1).1 In
this enzymatic system, the hydrogenation of acetaldehyde
occurs through the activation of the carbonyl group of acet-
aldehyde by the coordination of the carbonyl group to the
zinc active center, which is followed by hydride transfer
from NADH to acetaldehyde. Inspired by enzymatic reduc-
tion systems, various synthetic NAD(P)H analogues (Figure
1) have been developed and applied in organocatalyzed and
metal-catalyzed hydrogenation reactions of unsaturated
compounds, such as α,β-unsaturated carbonyls, imines, and
α-keto esters.3–7 Although several research groups have
studied the hydrogenation of unactivated aldehydes with
synthetic NAD(P)H analogues using Lewis8 or Brønsted9
acid catalysts, an efficient catalytic system has not yet been
developed.
DOI: 10.1055/s-0034-1378846; Art ID: st-2015-b0414-l
Abstract We have developed a method for the hydrogenation of un-
activated aldehydes, using a Hantzsch ester as a NAD(P)H analogue in
the presence of an electron-deficient triarylborane as a Lewis acid cata-
lyst. Thus, tris[3,5-bis(trifluoromethyl)phenyl]borane efficiently cata-
lyzes the hydrogenation of aliphatic aldehydes with a Hantzsch ester in
1,4-dioxane at 100 °C to give the corresponding aliphatic primary alco-
hols in up to 97% yield. Aromatic aldehydes also undergo the hydroge-
nation, even at 25 °C, to furnish the corresponding aromatic primary al-
cohols in up to 100% yield.
Key words alcohols, aldehydes, hydrogenation, NADH analogues, or-
ganoboranes
In nature, hydrogenation processes are typically medi-
ated by a combination of enzymes and organic reduction
cofactors such as NADH and NADPH.1,2 For example, in the
ethanol fermentation process, alcohol dehydrogenase pro-
On the other hand, organoboron compounds have been
used as Lewis acid catalysts for various organic transforma-
tions.10 In particular, electron-deficient boron compounds,
O
H
H
H
O
P
H2N
O
S(Cys 46)
O
O
N
Zn
O
S(Cys 174)
N
NAD+
O
OH
O
OH OH
N
NH2
NH
H
H
H
N
(His 67)
P
N
O
N
alcohol
dehydrogenase
O
OH OH
NADH
Scheme 1 Active site of alcohol dehydrogenase for the reduction of acetaldehyde with NADH
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2037–2041

2038
G. Hamasaka et al.
Letter
Synlett
tris[3,5-bis(trifluoromethyl)phenyl]borane (9) and the in-
vestigation of its Lewis acidity.16 They demonstrated that
the Lewis acidity of borane 9 is higher than that of B(C6F5)3.
We used borane 9 for the hydrogenation reaction; it provid-
ed the desired alcohol 8a in 70% yield (entry 5). These re-
sults show that borane 9 is the optimal catalyst for this hy-
drogenation reaction. We also tested other synthetic
NAD(P)H analogues (entries 6–10). The reaction was con-
ducted using Hantzsch ester 2 to afford 8a in 46% yield (en-
try 6). When N-benzyl-1,4-dihydronicotinamide (3), 5,6-di-
hydrophenanthridine (4), and dihydroacridines 5 and 6
O
O
O
NH2
RO
OR
N
N
H
Ph
1 R = Et
2 R = t-Bu
3
N
R
N
H
4
5 R = H
6 R = Me
Table 1 Screening of Reaction Conditions for the Hydrogenation of
Cyclohexanecarbaldehyde (7a)a
Figure 1 Typical synthetic NAD(P)H analogues
O
OH
cat. (5 mol%)
NADH
analogue
such as tris(pentafluorophenyl)borane, efficiently catalyze
various organic transformations (e.g., the Mukaiyama aldol
reaction and the Sakurai–Hosomi reaction) because of their
high oxophilic Lewis acidities.11 However, so far, the hydro-
genation of unactivated aldehydes with synthetic NAD(P)H
analogues using organoborane catalysts has been insuffi-
ciently investigated.8h,12–14 Ohno and co-workers have re-
ported that the reduction of benzaldehyde with a synthetic
NADH analogue does not take place in the presence of even
an excess amount of BF3.8h Although Stephane, Crudden,
and co-workers reported the formation of borohydrides by
the stoichiometric reaction of tris(pentafluorophenyl)bo-
rane with Hantzsch esters, the reactivity of the resulting
borohydrides for carbonyl reduction was not investigated.15
If a suitable organoborane catalyst is used for the hydroge-
nation of unactivated aldehydes with a synthetic NAD(P)H
analogue, the reaction should proceed efficiently to give al-
cohols. Therefore, we decided to use organoboranes as Lew-
is acid catalysts for the hydrogenation of unactivated alde-
hydes with a synthetic NADH analogue. Herein we report
the hydrogenation of unactivated aliphatic and aromatic al-
dehydes with a Hantzsch ester as a synthetic NADH ana-
logue in the presence of an electron-deficient triarylborane
catalyst to give the corresponding primary alcohols in ex-
cellent yields.
We initially examined the hydrogenation of cyclohexan-
ecarbaldehyde (7a) with Hantzsch ester 1 as a synthetic
NAD(P)H analogue, in the presence of BF3·OEt2 as a Lewis
acid catalyst, at 60 °C in toluene (Table 1, entry 1). The reac-
tion gave cyclohexanemethanol (8a) in a yield of only 2%.
When triethylborane and triphenylborane were used, the
hydrogenation was sluggish (entries 2 and 3). We then used
the electron-deficient triarylborane B(C6F5)3 for this hydro-
genation reaction. The hydrogenation took place to give 8a
in 28% yield (entry 4). We assumed that a triarylborane
with a Lewis acidity higher than that of B(C6F5)3 would
show higher catalytic activity in the hydrogenation. In
2012, Ashley and co-workers reported the synthesis of
H
H
+
H
solvent, temp
12 h
(1.5 equiv)
7a
Entry Catalyst
8a
Temp (°C) Yield (%)b
NADH analogue Solvent
1
2
BF3·OEt2
1
1
1
1
1
2
3
4
5
6
1
1
1
1
1
1
1
1
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
toluene
DCE
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
60
100
2
0
Et3B
3
Ph3B
0
4
(C6F5)3B
28
70
46
0
5
9
9
9
9
9
9
9
9
9
9
9
9
9
9
6
7
8
13
13
6
9
10
11
12
13
14
15
16
17
18
72
70
78
23
0
THF
1,4-dioxane
MeCN
DMF
DMSO
0
i-PrOH
0
1,4-dioxane
97
F3C
CF3
F3C
B
CF3
CF3
CF3
a Reaction conditions: cyclohexanecarbaldehyde (7a, 0.25 mmol), NADH
analogue (0.38 mmol, 1.5 equiv), catalyst (0.013 mmol, 5 mol%), solvent
(1 mL).
b Determined by GC analysis with an internal standard (biphenyl).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2037–2041

2039
G. Hamasaka et al.
Letter
Synlett
were used as synthetic NAD(P)H analogues, the hydrogena-
tion reaction did not proceed efficiently (entries 7–10).
These results indicate that Hantzsch ester 1 is the optimal
hydrogen donor for this hydrogenation.17 We then investi-
gated the effect of the solvent on the reaction (entries 11–
17). The reaction proceeded in 1,2-dichloroethane (DCE)
and tetrahydrofuran (THF) to give 8a in 72% and 70% yields,
respectively (entries 11 and 12). When 1,4-dioxane was
used as the solvent, the yield of 8a increased to 78% (entry
13). On the other hand, the use of acetonitrile as the solvent
led to a lower yield of 8a (entry 14). No reaction occurred in
N,N-dimethylformamide (DMF), dimethyl sulfoxide (DM-
SO), or isopropyl alcohol (entries 15–17). When the hydro-
genation was carried out in 1,4-dioxane at 100 °C, the de-
sired alcohol 8a was obtained in 97% yield (entry 18).
With the optimized reaction conditions in hand, we
next investigated the scope of aliphatic aldehydes that can
be used in this hydrogenation protocol (Scheme 2). The hy-
drogenation of cyclopentanecarbaldehyde (7b) was per-
formed at 100 °C in 1,4-dioxane to give cyclopentanemeth-
anol (8b) in 78% yield. Linear aliphatic aldehydes 7c–f un-
derwent the reaction to afford the corresponding alcohols
8c–f in 71–82% yields. The hydrogenation of 10-undecenal
(7g) proceeded to give 10-undecen-1-ol (8g) in 71% yield.
In this reaction, the terminal alkene group remained intact.
The reactions of the sterically hindered substrates 3,3-di-
methylbutylaldehyde (7h) and 1-adamantanecarbaldehyde
(7i) gave 3,3-dimethyl-1-butanol (8h) and 1-adaman-
tanemethanol (8i) in 88% and 70% yields, respectively.
Next, we studied the catalytic hydrogenation of aromat-
ic aldehydes with Hantzsch ester 1 (Scheme 3). Borane 9
also effectively catalyzed the hydrogenation of aromatic al-
dehydes 10 with Hantzsch ester 1, even at 25 °C, to give the
corresponding benzyl alcohols 11 in excellent yields.12 The
hydrogenation of benzaldehyde (10a) gave benzyl alcohol
(11a) in quantitative yield. Benzaldehyde derivatives bear-
ing electron-donating (R = Me and OMe) and electron-
withdrawing (R = CF3, CN, and NO2) groups in the para posi-
tion (10b–f) underwent hydrogenation to afford the corre-
sponding benzyl alcohols 11b–f in 92–100% yields. The re-
action of para-halogenated (R = F, Cl, Br, and I) benzalde-
hyde derivatives 10g–j gave the corresponding benzyl
alcohols 11g–j in excellent yields. In the hydrogenation of
4-acetylbenzaldehyde (10k), the aldehyde group was selec-
tively reduced; the ketone group remained intact. Ester and
alkene groups also remained intact under the reaction con-
ditions (11l,m). 3,4-Dimethoxybenzaldehyde (10o) and pi-
peronal (10p)18 underwent hydrogenation to afford alco-
hols 11o and 11p in 84% and 94% yields, respectively. The
O
O
O
OH
9 (5 mol%)
EtO
OEt
+
1,4-dioxane, 25 °C
12 h
Ar
H
Ar
H
N
H
H
10
1 (1.5 equiv)
11
OH
OH
OH
MeO
O
H
H
H
H
H
H
O
R
MeO
O
O
OH
11a R = H, 100% (48%)
11b R = Me, 96% (87%)
11c R = OMe, 92% (56%)
11d R = CF3, 100% (84%)
11e R = CN, 95% (93%)
11f R = NO2, 100% (91%)
11g R = F, 100% (52%)
11h R = Cl, 95% (92%)
11i R = Br, 100% (76%)
11j R = I, 100% (86%)
11k R = C(O)Me, 100% (68%)
11l R = C(O)OMe, 100% (74%)
11m R = CH=CH2, 100% (66%)
11n R = Ph, 100% (43%)
11p (94%)
11o (84%)
O
9 (5 mol%)
EtO
OEt
+
H
H
OH
R
H
1,4-dioxane, 100 °C
12 h
R
H
OH
H
N
H
H
7
1 (1.5 equiv)
8
H
OH
OH
H
OH
11q 100% (91%)
11r 100% (80%)
H
OH
C11H23
H
H
H
H
OH
X
H
8a 97% (53%)
8b 78% (39%)
8c 71%a (49%)
OH
H
H
H
OH
OH
Me
H
11s 100% (74%) 11t X = O, 100% (54%)
11u X = S, 100% (88%)
C9H19
H
C7H15
H
H
H
H
8d 82% (59%)
8e 80% (42%)
8f 81% (44%)
OH
OH
OH
OH
OH
H
H
H
OH
H
H
N
N
N
H
H
H
8
H
H
H
H
H
11v 0%, 28%a (12%)
11w 0%, 33%a (16%)
11x 91%b (46%)
8g 71% (58%)
8h 88%
8i 70% (52%)
Scheme 2 Scope of aliphatic aldehydes. Reagents and conditions: ali-
phatic aldehyde (7, 0.25 mmol), 1 (0.38 mmol, 1.5 equiv), 9 (0.013
mmol, 5 mol%), 1,4-dioxane (1 mL). The yields were determined by GC
analysis using an internal standard (biphenyl or mesitylene). Isolated
yields are described in parentheses. a Determined by 1H NMR analysis
using an internal standard (Cl2CHCHCl2).
Scheme 3 Scope of aromatic aldehydes. Reagents and conditions: aro-
matic aldehyde (10, 0.25 mmol), 1 (0.38 mmol, 1.5 equiv), 9 (0.013
mmol, 5 mol%), 1,4-dioxane (1 mL). The yields were determined by GC
analysis using an internal standard (biphenyl or mesitylene). Isolated
yields are described in parentheses. a The reaction performed at 100 °C.
b Determined by 1H NMR analysis using an internal standard (Cl2CHCHCl2).
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2037–2041

2040
G. Hamasaka et al.
Letter
Synlett
reaction of 2-naphthylaldehyde (10q), 1-naphthylaldehyde
(10r), and 2-methylbenzaldehyde (10s) took place to quan-
titatively afford alcohols 11q, 11r, and 11s, respectively. We
next tested the hydrogenation of heteroaromatic aldehydes.
The hydrogenations of furan-2-carbaldehyde (10t) and
thiophene-2-carbaldehyde (10u) were carried out at 25 °C
to afford alcohols 11t and 11u, respectively, in quantitative
yields. On the other hand, the reaction of pyridine deriva-
tives 10v and 10w did not proceed at 25 °C. When the reac-
tion temperature was elevated to 100 °C, the desired alco-
hols 11v and 11w were obtained in 28% and 33% yields, re-
spectively. The strong coordination of the pyridine nitrogen
to the boron center inhibited the reaction. On the other
hand, indole-2-carboxaldehyde (10x) underwent the reac-
tion at 25 °C to give 11x in 91% yield.
In summary, we have developed the tris[3,5-bis(trifluo-
romethyl)phenyl]borane-catalyzed hydrogenation of unac-
tivated aldehydes with a Hantzsch ester as a synthetic
NADH analogue. The hydrogenation of a variety of aliphatic
and aromatic aldehydes proceeded efficiently to give the
corresponding primary alcohols in good to excellent yields.
Mechanistic studies of this hydrogenation reaction are cur-
rently underway in our laboratory.19
(6) Catalytic transfer hydrogenation of imines with a Hantzsch
ester, see: Hoffmann, S.; Seayad, A. M.; List, B. Angew. Chem. Int.
Ed. 2005, 44, 7424.
(7) Catalytic transfer hydrogenation of α-keto esters with
Hantzsch ester, see: Yang, J. W.; List, B. Org. Lett. 2006, 8, 5653.
a
(8) Lewis acid mediated hydrogenation of unactivated aldehydes
with synthetic NADH analogues, see: (a) Zn:Creighton, D. J.;
Sigman, D. S. J. Am. Chem. Soc. 1971, 93, 6314. (b) Zn, Pb, Cb,
Cu:Shirai, M.; Chishina, T.; Tanaka, M. Bull. Chem. Soc. Jpn. 1975,
48, 1079. (c) Zn:Creighton, D. J.; Hajdu, J.; Sigman, D. S. J. Am.
Chem. Soc. 1976, 98, 4619. (d) Mg:Ohnishi, Y.; Kitami, M. Tetra-
hedron Lett. 1978, 19, 4033. (e) Zn, Ni:Hughes, M.; Prince, R. H. J.
Inorg. Nucl. Chem. 1978, 40, 703. (f) Zn:Hood, R. A.; Prince, R. H.
J. Chem. Soc., Chem. Commun. 1979, 163. (g) Mg:Mathis, R.;
Dupas, G.; Decormeille, A.; Quéguiner, G. Tetrahedron Lett.
1981, 22, 55. (h) B, Ti, Al, Zr, Sb:Ohno, A.; Ishihara, Y.; Ushida, S.;
Oka, S. Tetrahedron Lett. 1982, 23, 3185. (i) Mg:Dupas, G.;
Bourguignon, J.; Ruffin, C.; Queguiner, G. Tetrahedron Lett. 1982,
23, 5141. (j) Zn:Awano, H.; Tagaki, W. J. Chem. Soc., Chem.
Commun. 1985, 994. (k) Mg:Cazin, J.; Dupas, G.; Bourguignon, J.;
Quéguiner,
G.
Tetrahedron
Lett.
1986,
27,
2375.
(l) Zn:Engbersen, J. F. J.; Koudijs, A.; van der Plas, H. C. Bioorg.
Chem. 1988, 16, 215. (m) Mg, Zn, Nd, La, Eu, Al: Gelbard, G.; Lin,
J.; Roques, N. J. Org. Chem. 1992, 57, 1789.
(9) Brønsted acid mediated transfer hydrogenation of unactivated
aldehydes with synthetic NADH analogues, see: (a) Shinkai, S.;
Hamada, H.; Manabe, O. Tetrahedron Lett. 1979, 20, 1397.
(b) Fukuzumi, S.; Ishikawa, M.; Tanaka, T. J. Chem. Soc., Chem.
Commun. 1985, 1069. (c) Fukuzumi, S.; Ishikawa, M.; Tanaka, T.
Tetrahedron 1986, 42, 1021. (d) Ishikawa, M.; Fukuzumi, S. J.
Chem. Soc., Chem. Commun. 1990, 1353. (e) Kuroda, K.;
Nagamatsu, T.; Yanada, R.; Yoneda, F. J. Chem. Soc., Perkin Trans.
1 1993, 547.
Acknowledgment
This research project was supported by JST-ACCEL and JST-CREST pro-
grams.
(10) (a) Deloux, L.; Srebnik, M. Chem. Rev. 1993, 93, 763. (b) Duggan,
P. J.; Tyndall, E. D. J. Chem. Soc., Perkin Trans. 1 2002, 1325.
(c) Ishihara, K. In Boronic Acids; Hall, D. G., Ed.; Wiley-VCH:
Weinheim, 2005, 377–409. (d) Dimitrijević, E.; Taylor, M. S. ACS
Catal. 2013, 3, 945.
Supporting Information
Supporting information for this article is available online at
http://dx.doi.org/10.1055/s-0034-1378846.
S
u
p
p
ortioInfgrmoaitn
S
u
p
p
ortiInfogrmoaitn
(11) (a) Piers, W. E.; Chivers, T. Chem. Soc. Rev. 1997, 26, 345.
(b) Ishihara, K.; Yamamoto, H. Eur. J. Org. Chem. 1999, 527.
(c) Erker, G. Dalton Trans. 2005, 1883. (d) Piers, W. E. Adv.
Organomet. Chem. 2005, 52, 1.
(12) Very recently, Stephan and Ashley groups reported that the
combination of B(C6F5)3 and ethers (Et2O, i-Pr2O, and 1,4-diox-
ane) promoted the hydrogenation of ketones and limited alde-
hydes with H2 gas, see: (a) Mahdi, T.; Stephan, D. W. J. Am.
Chem. Soc. 2014, 136, 15809. (b) Scott, D. J.; Fuchter, M. J.;
Ashley, A. E. J. Am. Chem. Soc. 2014, 136, 15813.
(13) A review on B(C6F5)3-catalyzed reduction of unsaturated com-
pounds, see: Oestreich, M.; Hermeke, J.; Mohr, J. Chem. Soc. Rev.
2015, 44, 2202.
(14) Very recently, Chatterijee and Oestreich reported the B(C6F5)3-
catalyzed transfer hydrogenation of imines and related hetero-
cycles with cyclohexa-1,4-dienes, see: Chatterjee, I.; Oestreich,
M. Angew. Chem. Int. Ed. 2015, 43, 1965.
(15) Webb, J. D.; Laberge, V. S.; Geier, S. J.; Stephan, D. W.; Crudden,
C. M. Chem. Eur. J. 2010, 16, 4895.
(16) Herrington, T. J.; Thom, A. J. W.; White, A. J. P.; Ashley, A. E.
Dalton Trans. 2012, 41, 9019.
(17) We also tested the other hydrogen donors, see the Supporting
Information. The reaction with Hantzsch ester 2 provided the
best result.
References and Notes
(1) Berg, J. M.; Tymoczko, J. L.; Stryer, L. Biochemistry; W. H.
Freeman and Company: New York, 2002.
(2) Selected recent reviews on enzymatic reduction of carbonyl
compounds, see: (a) Kataoka, M.; Kita, K.; Wada, M.; Yasohara,
Y.; Hasegawa, J.; Shimizu, S. Appl. Microbiol. Biotechnol. 2003,
62, 437. (b) Jarboe, L. R. Appl. Microbiol. Biotechnol. 2011, 89,
249. (c) Rabinovitch-Deere, C. A.; Oliver, J. W. K.; Rodriguez, G.
M.; Atsumi, S. Chem. Rev. 2013, 113, 4611.
(3) Selected recent reviews on transfer hydrogenation using syn-
thetic NADH analogues as the hydrogen donors, see: (a) You, S.-
L. Chem. Asian J. 2007, 2, 820. (b) Ouellet, S. G.; Walji, A. M.;
Macmillan, D. W. C. Acc. Chem. Res. 2007, 40, 1327. (c) Rueping,
M.; Sugiono, E.; Schoepke, F. R. Synlett 2010, 852. (d) Rueping,
M.; Dufour, J.; Schoepke, F. R. Green Chem. 2011, 13, 1084.
(e) Zheng, C.; You, S.-L. Chem. Soc. Rev. 2012, 41, 2498.
(4) McSkimming, A.; Colbran, S. B. Chem. Soc. Rev. 2013, 42, 5439.
(5) Catalytic transfer hydrogenation of α,β-unsaturated carbonyls
with a Hantzsch ester, see: (a) Yang, J. W.; Hechavarria Fonseca,
M. T.; List, B. Angew. Chem. Int. Ed. 2004, 43, 6660. (b) Yang, J.
W.; Hechavarria Fonseca, M. T.; Vignola, N.; List, B. Angew.
Chem. Int. Ed. 2005, 44, 108.
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(18) Typical Procedure for the Hydrogenation Reaction (10p,
Scheme 3)
CH2OH), 5.94 (s, 2 H, OCH2O), 6.77 (d, J = 8.1 Hz, 2 H, ArH), 6.80
(d, J = 8.1 Hz, 2 H, ArH), 6.85 (s, 1 H, ArH). 13C NMR (100 MHz,
CDCl3): δ = 65.1, 101.0, 107.8, 108.1, 120.4, 134.8, 147.0, 147.7.
MS (EI): m/z = 152 [M]+.
In a glovebox, piperanal (10p, 38 mg, 0.25 mmol) and Hantzsch
ester 1 (95 mg, 0.38 mmol) were added to a solution of tris[3,5-
bis(trifluoromethyl)phenyl]borane (9, 8.1 mg, 0.013 mmol) in
dry 1,4-dioxane (1 mL). After the reaction mixture was stirred
at 25 °C for 12 h, the solvent was removed by evaporation under
reduced pressure. The obtained crude material was purified by
silica gel column chromatography (eluent: hexane–EtOAc, 9:1)
to give piperonyl alcohol (11p, 36 mg, 94%) as a colorless solid.
1H NMR (396 MHz, CDCl3): δ = 2.02 (br s, 1 H, OH), 4.55 (s, 2 H,
(19) The reviewer pointed out the possible participation of borohy-
dride species in the catalytic cycle (see ref. 15). However, the
preliminary NMR experiment of borane 9 with Hantzsch ester 1
did not show the formation of borohydride species. Detailed
mechanistic studies including DFT calculation are under inves-
tigation and will be reported in due course.
© Georg Thieme Verlag Stuttgart · New York — Synlett 2015, 26, 2037–2041