Copper-catalyzed borylation of α-alkoxy allenes with bis(pinacolato)diboron: Efficient synthesis of 2-boryl 1,3-butadienes

Article abstract of DOI:10.1002/anie.201306843

Something solid to build on: 2-Boryl 1,3-butadienes with various substitution patterns were formed in good to high yields in a copper-catalyzed borylation of α-alkoxy allenes with bis(pinacolato)diboron (see scheme; Bn=benzyl, pin=pinacolate, L is an N-he

Full text of DOI:10.1002/anie.201306843

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DOI: 10.1002/anie.201306843
Synthetic Methods
Copper-Catalyzed Borylation of a-Alkoxy Allenes with
Bis(pinacolato)diboron: Efficient Synthesis of 2-Boryl
1,3-Butadienes**
Kazuhiko Semba, Tetsuaki Fujihara, Jun Terao, and Yasushi Tsuji*
Organoboranes are useful synthetic intermediates in organic
synthesis, with utility in carbon–carbon[1] and carbon–hetero-
atom[2] bond-forming reactions. The hydroboration[3] of
carbon–carbon unsaturated bonds is one of the most powerful
methods available for the synthesis of a wide variety of
organoboranes. We recently reported the copper-catalyzed
selective hydroboration of allenes by the use of bis(pinaco-
lato)diboron (B2(pin)2) as a borylation reagent.[4] In the
reaction, a b-boryl s-allyl copper intermediate was cleanly
generated by the insertion of an allene into a boryl copper
catalytic species (Scheme 1a).[4a] On the basis of the pioneer-
ing studies by Ito, Sawamura, and co-workers on the copper-
catalyzed borylation of substrates containing oxygen-based
leaving groups,[5] we anticipated that 2-boryl 1,3-butadienes
could be efficiently synthesized by the borylation of allenes
bearing a suitable leaving group at the a-position (Sche-
me 1b).
Boryl-substituted 1,3-butadiene derivatives are poten-
tially useful building blocks.[6] 1-Boryl 1,3-butadienes can be
readily synthesized by the hydroboration of 1,3-enynes and
then employed as useful boryl compounds.[7] In sharp
contrast, the synthetic methods available to date for the
synthesis of 2-boryl 1,3-butadienes are not so efficient.[8] For
example, elaborate methods, including the enyne metathesis
of alkynyl boranes[8a–c] (Scheme 2a), palladium-catalyzed
cross-coupling reactions of (Z)-1-halo 1-alkenyl boranes[8d]
or 1,1-diboryl 1-alkenes[8e] (Scheme 2b), reactions of alkynyl
Scheme 1. Approaches to the synthesis of 1,3-dienyl boranes from
allenes. LG=leaving group.
[*] Prof. Dr. K. Semba, Prof. Dr. T. Fujihara, Prof. Dr. Y. Tsuji
Department of Energy and Hydrocarbon Chemistry
Graduate School of Engineering, Kyoto University
Kyoto 615-8510 (Japan)
Scheme 2. Previously reported approaches to 2-boryl 1,3-butadiene
derivatives. TMS=trimethylsilyl.
E-mail: ytsuji@scl.kyoto-u.ac.jp
Homepage: http://twww.ehcc.kyoto-u.ac.jp/
Prof. Dr. K. Semba
boranes with alkynes[8f] (Scheme 2c), and hydroboration
followed by migration[8g] (Scheme 2d), have been reported;
however, the variety of available 2-boryl 1,3-butadienes has
remained quite limited. Thus, more efficient and general
synthetic methods are highly desirable. Herein, we report the
straightforward copper-catalyzed borylation[9] of a-alkoxy
allenes with B2(pin)2 to afford 2-boryl 1,3-butadienes with
various substitution patterns.
Present Address: Department of Material Chemistry
Graduate School of Engineering, Kyoto University
Kyoto 615-8510 (Japan)
[**] This research was supported by a Grant-in-Aid for Scientific
Research on Innovative Areas (“Organic Synthesis Based on
Reaction Integration” and “Molecular Activation Directed Toward
Straightforward Synthesis”) from MEXT (Japan), and in part by the
Mitsubishi Foundation. K.S. is grateful for a JSPS Research
Fellowship for Young Scientists.
= =
We investigated the borylation of Me2C C CCH2OBn
Supporting information for this article is available on the WWW
under http://dx.doi.org/10.1002/anie.201306843.
(1a) with B2(pin)2 in THF at room temperature in the
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Table 1: Optimization of the reaction conditions for the copper-catalyzed
borylation of 1a.[a]
Table 2: Synthesis of various 2-boryl 1,3-butadienes.[a]
Entry Substrate
Product
Yield [%][b]
85
Entry
L
OR
Yield of 2a [%][b]
1
2
3
4
5
6
7
IMes
IPr
OBn (1a)
OBn (1a)
OBn (1a)
OBn (1a)
O(n-C6H13) (1a1)
OCO2Me (1a2)
OAc (1a3)
81
1
1b
2b
92
IPrCPh
95 (89)[c]
3
xantphos
38
94
96
8
IPrCPh
3
2
3
1c
1d
2c
2d
71
90
IPrCPh
3
IPrCPh
3
[a] Reaction conditions: [LCuCl] (0.0050 mmol, 2.0 mol%), KOtBu
(0.025 mmol, 10 mol%), B2(pin)2 (0.28 mmol), an allene (0.25 mmol),
THF (0.50 mL), room temperature, 30 min. [b] The yield was determined
by GC with an internal standard. [c] The yield of isolated 2a is given in
parentheses. Bn=benzyl.
59
4
5
1e
1 f
2e
2 f
(67)[c]
62
(78)[c,d]
presence of copper catalysts (Table 1, entries 1–4). First,
commercially available copper complexes bearing an N-
heterocyclic carbene (NHC) ligand were evaluated as cata-
lysts. The corresponding 1,1-disubstituted 2-boryl 1,3-buta-
diene 2a was obtained in 81% yield with the catalyst
[(IMes)CuCl] and in 92% yield with [(IPr)CuCl] (Table 1,
entries 1 and 2; see Scheme 3 for the structures of ligands
6
7
1g
1h
2g
2h
67
82
À
Á
used in this study). A bulky NHC complex, [ IPrCPh CuCl],
was found to be a better catalyst. It promoted the formation
3
8
1i
1j
1k
1l
2i
2j
2k
2l
87
9[e]
99
10[f]
11[h]
63[g]
96[i]
Scheme 3. Structures of the ligands used in this study.
of 2a in 95% yield and enabled the isolation of pure 2a in
89% yield (Table 1, entry 3). However, with [(xant-
phos)CuCl] as the catalyst, the yield decreased to 38%
12[j]
1m
2m
76[k]
À
(Table 1, entry 4). As leaving groups for the allene, O(n-
À
À
Á
C6H13) and OCO2Me were found to be effective (entries 5
[a] Reaction conditions: [ IPrCPh CuCl] (0.0050 mmol, 2.0 mol%),
KOtBu (0.025 mmol, 10 mol%), B2(pin)2 (0.28 mmol), an allene
(0.25 mmol), THF (0.50 mL), room temperature, 30 min. [b] Yield of the
isolated product. [c] The catalyst [(IPr)CuCl] (0.0050 mmol, 2.0 mol%)
3
À
and 6). In contrast, with the leaving group OAc, 2a was
formed in only 8% yield (Table 1, entry 7). Owing to the ease
of synthesis and good stability of the corresponding allene
substrates, OBn was chosen as the preferred leaving group.[10]
The reaction was carried out with various allenes bearing
an a-OBn leaving group under the optimized reaction
conditions (Table 2). When the 1,1-disubstituted allene 1b
was used, 2b was isolated in pure form in 85% yield (Table 2,
entry 1). The 3-butyl- and 3-phenyl-substituted allenes 1c and
1d afforded the corresponding 3-substituted 2-boryl 1,3-
butadienes 2c and 2d selectively in high yields (Table 2,
entries 2 and 3). The a,a-disubstituted allenes 1e and 1 f were
converted selectively into the 2-boryl butadienes 2e and 2 f
containing two substituents at the 4-position in 59 and 62%
yield, respectively (Table 2, entries 4 and 5 in parentheses). In
these reactions, [(IPr)CuCl] also showed good catalytic
À
Á
was used instead of [ IPrCPh CuCl]. [d] The reaction was carried out at
108C. [e] The reaction was carried out at 608C for 14 h. [f] The reaction
was carried out at 08C for 11 h. [g] E/Z 96:4. [h] The reaction was carried
out at À408C for 17 h. [i] E/Z 90:10. [j] The catalyst [(xantphos)CuCl]
3
À
Á
(0.0050 mmol, 2.0 mol%) was used instead of [ IPrCPh CuCl]. [k] Z/E
3
96:4.
activity (Table 2, entries 4 and 5). N-tert-butoxycarbonyl (N-
Boc) and ketal moieties were tolerated under these reaction
conditions, with the formation of 2g and 2h in 67 and 82%
yield, respectively (Table 2, entries 6 and 7), and the highly
substituted 2-boryl 1,3-butadienes 2i and 2j were obtained
successfully in high yield from 1i and 1j (Table 2, entries 8
and 9). It was anticipated that the borylation of unsymmetri-
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cally a,a-disubstituted allenes, such as 1k and 1l, would be
challenging, since E/Z stereoisomeric mixtures could be
produced. However, in practice, (E)-2k and (E)-2l were
obtained in 63 and 96% yield, respectively, with high
stereoselectivity (E/Z 96:4 and 90:10; Table 2, entries 10
and 11). Furthermore, the allene 1m bearing a secondary
alkyl substituent at the 1-position was successfully trans-
formed into (Z)-2m in 76% yield with high stereoselectivity
(Z/E 96:4) by the use of [(xantphos)CuCl] as the catalyst
(Table 2, entry 12). Surprisingly, the products shown in
Table 2, including rather simple compounds, are all new
compounds, which highlights the impracticality of current
methods for the preparation of 2-boryl 1,3-butadienes with
various substitution patterns. Furthermore, the reactions
proceeded smoothly with much lower catalyst loadings:
a copper alkoxide ([LCuOBn]).[15] Finally, s-bond metathesis
of [LCuOBn] with B2(pin)2 regenerates a boryl copper species
3, and the catalytic cycle is closed.
To date, the synthetic utility of 2-boryl 1,3-butadienes 2
has not been fully examined owing to the paucity of these
compounds. Diels–Alder reactions[8a,h,16] of 2b and 2e with 5a
afforded cyclic vinyl boranes 6b and 6e in high yield
(Scheme 6). Furthermore, the hetero-Diels–Alder reaction
of 2b with 5b proceeded smoothly to give the boryl-
substituted heterocycle 7b in 85% yield. Suzuki–Miyaura
À
Á
0.01–0.05 mol% of [ IPrCPh CuCl] (Scheme 4a). Gratify-
ingly, the procedure is amenable to scale-up, as shown by
two reactions carried out on a gram scale (Scheme 4b).
A possible catalytic cycle is shown in Scheme 5. First,
a boryl copper species 3 is generated in situ by the reaction of
3
Scheme 6. Diels–Alder reactions of 2.
coupling of 2b with 8a and 8b afforded the trisubstituted 1,3-
butadiene 9ba and the triene 9bb in good yield (Scheme 7a).
The a,b-unsaturated ketone 10 f was obtained by the treat-
ment of 2 f with H2O2 (Scheme 7b), and the functionalized
1,3-diene 11 f was obtained in 63% yield from 2 f by
Scheme 4. a) Reactions carried out with low catalyst loadings.
b) Gram-scale synthesis.
a copper alkoxide with B2(pin)2.[11] As shown previously,[4a]
3
inserts into an allene to afford s-allyl copper intermediates 4
and 4’. Although the distribution of 4 and 4’ would depend on
the substituents on the allene, they can exchange by a fast h1–
h3 interconversion.[13] b-Elimination[14] of the benzyloxy
moiety from 4 occurs to give 2-boryl 1,3-butadienes 2 and
Scheme 7. Further transformations of the 2-boryl 1,3-butadienes 2.
SPhos=2-dicyclohexylphosphanyl-2’,6’-dimethoxybiphenyl.
homologation[17] followed by the allylboration of benzalde-
hyde (Scheme 7c).
In conclusion, we have developed an efficient and general
method for the synthesis of 2-boryl 1,3-butadienes by the
copper-catalyzed borylation of a-alkoxy allenes with B2(pin)2.
The reaction can be conducted with low catalyst loadings and
on a gram scale. 2-Boryl 1,3-butadienes are useful intermedi-
Scheme 5. A possible catalytic cycle.
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Experimental Section
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À
Á
Typical procedure: [ IPrCPh CuCl] (4.9 mg, 0.0050 mmol, 2.0 mol%)
and B2(pin)2 (71 mg, 0.28 mmol) were placed in an oven-dried 20 mL
Schlenk flask, and the flask was evacuated for 30 min. The flask was
evacuated and backfilled with argon three times. THF (0.50 mL) and
KOtBu (25 mL of a 1.0m solution in THF, 10 mol%) were added, and
the resulting mixture was stirred at room temperature for 5 min. An
allene (0.25 mmol) was then added, and the mixture was stirred at
room temperature for 30 min. After the reaction, the mixture was
filtered through a pad of Celite and silica gel, and all volatiles were
removed in vacuo. The product was obtained by silica-gel column
chromatography (eluent: hexane/Et2O).
3
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Received: August 5, 2013
Published online: October 2, 2013
Keywords: allenes · boron · copper · organoboranes ·
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