Iron-catalyzed boration of allylic alcohols with H3BO3 as an additive

Article abstract of DOI:10.1080/00397911.2017.1422764

A method for the synthesis of allylboronates by iron-catalyzed boration of allylic alcohols with H₃BO₃ as an additive is developed. The introduction of H₃BO₃ promotes the cleavage of C?O bond in allylic alcohols

Full text of DOI:10.1080/00397911.2017.1422764

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Iron-catalyzed boration of allylic alcohols with
H3BO3 as an additive
Yuhan Zhou, Huan Wang, Yang Liu, Yilong Zhao, Chunxia Zhang & Jingping
Qu
To cite this article: Yuhan Zhou, Huan Wang, Yang Liu, Yilong Zhao, Chunxia Zhang & Jingping
Qu (2018) Iron-catalyzed boration of allylic alcohols with H3BO3 as an additive, Synthetic
Communications, 48:7, 795-801, DOI: 10.1080/00397911.2017.1422764
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SYNTHETIC COMMUNICATIONS®
2018, VOL. 48, NO. 7, 795–801
https://doi.org/10.1080/00397911.2017.1422764
Iron-catalyzed boration of allylic alcohols with H3BO3 as an
additive
Yuhan Zhou , Huan Wang , Yang Liu , Yilong Zhao , Chunxia Zhang
and Jingping Qu
,
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and Technology, Dalian University of
Technology, Dalian, P. R. China
ABSTRACT
ARTICLE HISTORY
Received 9 December 2017
A
method for the synthesis of allylboronates by iron-catalyzed
boration of allylic alcohols with H3BO3 as an additive is developed.
The introduction of H3BO3 promotes the cleavage of C‒O bond in
allylic alcohols obviously. Functional groups, such as fluoro, chloro,
bromo, alkyl, and alkoxy, are tolerated well. Thus, various allylbor-
onates are obtained in acceptable yield.
KEYWORDS
Allylboronates; allylic
alcohols; boration; boric
acid; iron-catalysis
GRAPHICAL ABSTRACT
Introduction
Owing to the importance in synthetic organic chemistry,[1] the synthesis of allylboronates has
received much attention.[2] Compared with the transmetalation of allylic lithiums or allylic
magnesiums to the boron,[3] the traditional method to obtain allylboronates, the metal cata-
lyzed boration of allylic derivatives or 1,3-dienes has been found to be an efficient way owing
to the widely functional group tolerance and mild reaction conditions. Inspired by the pio-
neering work of Miyaura et al. on palladium catalyzed boration of allylic esters,[4] diverse
allylic boronates have been synthesized through palladium, nickel, or copper catalyzed bora-
tion of allylic halides or allylic esters.[5] Compared with allylic esters and halides, the direct use
of allylic alcohols is more beneficial. One reason is that allylic esters and halides are derivatives
of allylic alcohols, which is easier to obtain. The other one is that water is generated as a co-
product in the reaction of allylic alcohols whereas allylic esters and halides afford correspond-
ing salt wastes. Although Pd-catalyzed versions have been intensively studied,[6] direct bora-
tion of allylic alcohol through more economic and sustainable approaches, such as those
catalyzed/promoted by base-metal salts or copper,[7] are scarce. To promote the cleavage of
C‒O bond in allylic alcohols, an efficient way is adding some Lewis acids,[8] such as boron
reagents,[9] as additives. Recently, our group also focused on the boration of alkenes using
CONTACT Yuhan Zhou
zhouyh@dl.cn
State Key Laboratory of Fine Chemicals, School of Pharmaceutical Science and
Technology, Dalian University of Technology, Dalian 116024, P. R. China.
Color versions of one or more of the figures in the article can be found online at www.tandfonline.com/lsyc.
Supplemental data can be accessed on the publisher’s website.
© 2018 Taylor & Francis

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Y. ZHOU ET AL.
low cost, low toxicity and environmentally friendly iron catalyst.[10] As a consequence, the
synthesis of allylic boronates through FeCl2-catalyzed boration of allylic esters was
achieved.[10c] However, the reaction of allylic alcohols gave poor yield in the previous study.
In this context, we describe our further study on the iron-catalyzed direct boration of allylic
alcohols with H3BO3 as an additive to promote the cleavage of C‒O bond.
Results and discussion
The iron-catalyzed direct boration of allylic alcohols was initiated with 2-phenylprop-2-en-
1-ol (1a) as a model substrate. At the outset, several boron reagents were investigated as
additives to promote the cleavage of C‒O bond (Table 1). Under the already established
conditions for the boration of allylic esters,[10c] the reaction of allylic alcohols gave poor
yield (Table 1, entry 1). To our delight, the introduction of PhB(OH)2 improved the yield
obviously (Table 1, entry 2). The highest yield was achieved when 0.5 eq. of H3BO3 was
used while B(OMe)3 had almost no effect on the reaction (Table 1, entries 3 and 4). Both
increasing and decreasing the amount of H3BO3 resulted in the decrease of the yield
1
(Table 1, entries 5 and 6). Analysis of the crude product by H NMR showed that 1a
was totally consumed and some new materials with similar signals with 1a were formed
besides 3a. We speculated they were adducts of 1a and the boron species. That is why high
conversion of 1a was determined in all cases.
It is well known that the ligands may adjust the electronic and steric character of the
metal center, thus affecting the activity and selectivity of the catalyst. So the effect of the
ligands was explored (Table 2). Without additional ligand, the reaction can also proceed
but with a lower yield (Table 2, entry 1). In the screened phosphine and nitrogen ligands
(Table 2, entries 2–10), (n-Bu)3P gave the highest yield (Table 2, entry 5). Upon slightly
increasing the ligand loading to 24 mol%, a higher yield of 68% was achieved (Table 2,
entry 11). But the yield was not increased anymore when the ligand loading was further
increased to 30 mol% (Table 2, entry 12). In addition, similar to our previous reports on
the iron catalyzed boration of alkenes,[10] no desired product was detected in the absence
of a base (Table 2, entry 13).
Table 1. Optimization of boron reagents.a
Entry
Boron reagent
Yieldb (%)
1
–
16
57
62
17
37
32
2
PhB(OH)2
H3BO3
B(OMe)3
H3BO3
H3BO3
3
4
5c
6d
aReaction conditions: 1a (0.3 mmol), 2 (0.45 mmol), FeCl2 (0.03 mmol), PPh3 (0.066 mmol), t-BuOK (0.3 mmol), boron reagent
(0.5 eq.) in THF (2 mL) at 65 °C for 14 h.
bYield was determined by 1H NMR with 1,1,2,2-tetrachloroethane as an internal standard.
cH3BO3 (0.09 mmol, 0.3 eq.).
dH3BO3 (0.3 mmol, 1 eq.).
THF, tetrahydrofuran.

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Table 2. Optimization of ligands.a
Entry
Ligand
Yieldb(%)
1
2
–
51
56
35
55
66
59
54
20
55
44
68
67
0
Ph3P (20 mol%)
3
Xantphos (10 mol%)
DPPF (10 mol%)
(n-Bu)3P (20 mol%)
(t-Bu)3P (20 mol%)
Tricyclohexylphosphine (20 mol%)
X-phos (20 mol%)
4
5
6
7
8
9
1,10-Phenanthroline (10 mol%)
TMEDA (10 mol%)
10
11
12
13c
(n-Bu)3P (24 mol%)
(n-Bu)3P (30 mol%)
(n-Bu)3P (24 mol%)
aReaction conditions: 1a (0.6 mmol), 2 (0.9 mmol), FeCl2 (0.06 mmol), ligand, t-BuOK (0.6 mmol), H3BO3 (0.3 mmol) in THF
(2 mL) at 65 °C for 24 h.
bYield was determined by 1H NMR with 1,1,2,2-tetrachloroethane as an internal standard.
cWithout t-BuOK.
Xantphos, 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene; X-phos, 2-dicyclohexylphosphino-20,40,60-triisopropylbiphenyl.
DPPF, 1,10-bis(diphenylphosphino)ferrocene; TMEDA, tetramethylethylenediamine.
The catalytic performance of other transition metal salts were also examined (Table 3).
Compared with FeCl2, other metal chlorides, such as CuCl, PdCl2, and NiCl2, exhibited lower
activity (Table 3, entries 1–3). The use of high-purity (99.99%) FeCl2 as the catalyst gave a
higher yield of 70% (Table 3, entry 5), while no desired product was obtained without FeCl2
(Table 3, entry 6). The above results suggest that the reaction is catalyzed by iron.
In addition, the influence of solvent was explored (Table 4). In general, ethers gave
better results (Table 4, entries 1–4), and tetrahydrofuran (THF) was the best one (Table 4,
entry 1). A lower yield was obtained when DMF was used (Table 4, entry 5).
Table 3. Optimization of transition metal catalysts.a
Entry
Catalysis
Yieldb (%)
1
CuCl
PdCl2
NiCl2
FeCl2
FeCl2
–
29
13
53
68
70
0
2
3
4
5c
6
aReaction conditions: 1a (0.6 mmol), 2 (0.9 mmol), catalysis (0.06 mmol), (n-Bu)3P (0.144 mmol), t-BuOK
(0.6 mmol), H3BO3 (0.3 mmol) in THF (2 mL) at 65 °C for 24 h.
bYield was determined by 1H NMR with 1,1,2,2-tetrachloroethane as an internal standard.
cFeCl2 (99.99%, 10 mol%).
THF, tetrahydrofuran.
Table 4. Optimization of reaction solvents.a
Entry
Solvent
Yieldb (%)
1
2
3
4
5
THF
68
60
48
62
37
t-BuOMe
dioxane
1,2-Dimethoxyethane
DMF
aReaction conditions: 1a (0.6 mmol), 2 (0.9 mmol), FeCl2 (0.06 mmol), (n-Bu)3P (0.144 mmol), t-BuOK
(0.6 mmol), H3BO3 (0.3 mmol) in solvent (2 mL) at 65 °C for 24 h.
bYield was determined by 1H NMR with 1,1,2,2-tetrachloroethane as an internal standard.
DMF, dimethylformamide; THF, tetrahydrofuran.

798
Y. ZHOU ET AL.
Table 5. Reaction of variously substituted allylic alcohols with B2pin2.
Having established the optimized reaction conditions, the scope in terms of allylic alco-
hols was explored (Table 5). Various allylic alcohols bearing either electron-withdrawing or
electron-donating groups were converted smoothly into the corresponding allylboronates
in acceptable yield. Functional groups, such as chloro, fluoro, bromo, alkyl, and alkoxy,
were tolerated well. 2-(Naphthalen-2-yl)prop-2-en-1-ol afforded the corresponding
product in 48% yield. α-Substituted allylic alcohols were also converted into the desired
products in moderate to good yields. It is worth pointing out that a mixture of E/Z
configuration products was obtained for α-mono-substituted substrates.
Scheme 1. Proposed mechanism for iron-catalyzed boration of allylic alcohol.

SYNTHETIC COMMUNICATIONS®
799
On the basis of the previous study on the mechanism of boration,[11] addition/
elimination of allylic carbonates[5a,b] and activation of hydroxy group by boron
reagents,[6e,9a,b] a possible reaction mechanism using 1a as a representative substrate was
shown in Scheme 1. The complex A, formed through addition of t-BuOK to B2pin2, was
suffered a B‒B bond cleavage with the release of t-BuOBpin to generate the FeB
intermediate (B). Meanwhile, 1a was coordinated to H3BO3 to form a complex C, which
=
was further coordinated to the intermediate B followed by the insertion of C C double
bond to the Fe–B bond to generate intermediate D. Finally, the product was obtained after
the release of KB(OH)4 with regeneration of the active Fe catalyst. Although a boronate
t-BuOBpin was generated, it was not an efficient activator for hydroxyl group in this
reaction. That agrees with the low activity of B(OMe)3 (Table 1, entry 4).
Conclusion
In summary, the first iron-catalyzed boration of allylic alcohols with H3BO3 as an additive
has been described. Various allylic alcohols bearing either electron-withdrawing or
electron-donating groups, such as fluoro, chloro, bromo, alkyl, and alkoxy, were converted
smoothly into corresponding allylboronates in acceptable yield. This method was also
suitable for α -substituted allylic alcohols, and a mixture of E/Z configuration products
was obtained for α -mono-substituted substrates.
Experimental
1H NMR (400 MHz) were recorded on a Bruker AVANCE II-400 spectrometer with
chemical shifts reported as ppm (in CDCl3, with TMS as an internal standard). 13C
NMR (101 MHz) were recorded on a Bruker AVANCEII-400 spectrometer with chemical
shifts reported as ppm (in CDCl3, with CDCl3 as an internal standard). High resolution
mass spectra (ESI) were recorded on a Micromass Waters Q-TOF Microspectrometer.
Unless otherwise noted, all reactions were performed under argon using Schlenk line
techniques or in a glovebox with magnetic stirring. Solvents were dried by passage through
an activated alumina column under argon. Column chromatography was performed on
silica gel (200–300 mesh). High-purity FeCl2 (beads, 99.99%, Sigma-Aldrich) powder
was prepared using a mortar and pestle in a glovebox. Other reagents and the substrates
were purchased and used as received.
General procedure for the synthesis of allylboronates (3)
To a Schlenk tube equipped with a magnetic stir bar and charged with FeCl2 (13 mg,
0.1 mmol) was added THF (6 mL), followed by aryl allylic alcohols (1.0 mmol), H3BO3
(30.9 mg, 0.5 mmol), bis(pinacolato)diboron (381 mg, 1.5 mmol), t-BuOK (113 mg,
1.0 mmol) and P(Bu-n)3 (48.6 mg, 0.24 mmol). The resulting mixture was stirred at
65 °C for 24 h. Then, brine (20 mL) was added and the aqueous layer was extracted with
EtOAc (3 � 20 mL). The combined organic layers were dried over Na2SO4 and the solvent
was removed in vacuum. The resultant crude product material was purified by flash
chromatography using the appropriate gradient of petroleum ether and EtOAc.
2-(2-Phenylallyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3a)[10c]
Colorless liquid, yield 51%; 1H NMR (400 MHz, CDCl3, Me4Si) δ 7.52–7.50 (m, 2H), 7.30–
7.26 (m, 2H), 7.35–7.31 (m, 1H), 5.40 (d, J ¼ 1.3 Hz, 1H), 5.14 (d, J ¼ 1.3 Hz, 1H), 2.21

800
Y. ZHOU ET AL.
(s, 2H), 1.20 (s, 12H); 13C NMR (101 MHz, CDCl3) δ 144.4, 141.9, 128.1, 127.2, 125.9,
112.2, 83.4, 24.6.
Funding
The authors gratefully acknowledge the financial support of the National Natural Science
Foundation of China (Nos. 21576041 and 21231003) and the program for Changjiang Scholars
and Innovative Research Team in University (No. IRT13008).
ORCID
Yuhan Zhou
Huan Wang
Yang Liu
http://orcid.org/0000-0002-1860-8669
http://orcid.org/0000-0001-5792-7841
http://orcid.org/0000-0002-5860-1437
http://orcid.org/0000-0001-7938-8973
Yilong Zhao
Chunxia Zhang
Jingping Qu
http://orcid.org/0000-0002-5197-4679
http://orcid.org/0000-0002-7576-0798
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