Substrate-Controlled Regio- and Stereoselective Synthesis of Boron-Substituted 1,4-Dienes via Copper-Catalyzed Boryl-Allylation of Alkynes with Allyl Phosphates and Bis(pinacolato)diboron

Article abstract of DOI:10.1021/acscatal.5b01441

Boron-substituted 1,4-dienes are versatile building blocks for the synthesis of 1,4-dienes (skipped alkenes), a common motif in bioactive natural products, because of their utility in the Suzuki-Miyaura coupling reaction and conjugate additions. A method for the synthesis of boron-substituted 1,4-dienes by means of copper-catalyzed boryl-allylation of alkynes with allyl phosphate and bis(pinacolato)diboron has been developed. The regioselectivity with respect to the alkyne and allyl phosphate depends on the structures of both the alkyne and the allyl phosphate. For alkynes bearing at least one aryl substituent, addition of borylcopper to the alkyne mainly generates a β-boryl-α-aryl-α-alkenylcopper species, whose subsequent reaction with secondary allyl phosphates provides γ-(4E)-selective boron-substituted 1,4-dienes, and with primary allyl phosphates provided α-selective boron-substituted 1,4-dienes. On the other hand, the α-boryl-α-aryl-β-alkenylcopper species formed as a minor intermediate from aryl alkyl acetylenes and the β-borylalkenylcopper species formed from dialkyl acetylenes show poor regioselectivity with respect to the secondary allyl phosphate and produce a mixture of α- and γ-selective boron-substituted 1,4-dienes. However, their reactions with the primary allyl phosphate are highly γ-selective. For all of the α-selective reactions, the configuration of the C=C bond of the allyl phosphate was retained in the products. The palladium-catalyzed cross-coupling of boron-substituted 1,4-dienes and aromatic, alkenyl, and alkynyl halides gave polyenes or enynes in 68%-95% yield, demonstrating that these boron-substituted 1,4-dienes are versatile building blocks for the synthesis of 1,4-dienes.

Full text of DOI:10.1021/acscatal.5b01441

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Article
Substrate-Controlled Regio- and Stereoselective Synthesis of
Boron-Substituted 1,4-dienes via Copper-Catalyzed Boryl-Allylation
of Alkynes with Allyl Phosphates and Bis(pinacolato)diboron
Huai-Yu Bin, Xiao Wei, Jing Zi, Ya-Jie Zuo, Tian-Chi Wang, and Chongmin Zhong
ACS Catal., Just Accepted Manuscript • DOI: 10.1021/acscatal.5b01441 • Publication Date (Web): 29 Sep 2015
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SubstrateꢀControlled Regioꢀ and Stereoselective
Synthesis of BoronꢀSubstituted 1,4ꢀdienes via
CopperꢀCatalyzed BorylꢀAllylation of Alkynes with
Allyl Phosphates and Bis(pinacolato)diboron
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Huai-Yu Bin,† Xiao Wei,† Jing Zi,† Ya-Jie Zuo,† Tian-Chi Wang,‡ and Chong-Min Zhong*,†,‡
†Department of Applied Chemistry, College of Science, Northwest A&F University, Yangling
712100, PR China
‡Department of Chemistry, College of Chemistry and Chemical Engineering, Harbin Normal
University, Harbin 150025, PR China
ABSTRACT: Boronꢀsubstituted 1,4ꢀdiene is a versatile building block for the synthesis of 1,4ꢀ
diene (skipped alkene), which is a common motif in bioactive natural products, due to its utility
in the Suzuki−Miyaura coupling reaction and conjugate additions. A method for the synthesis of
boronꢀsubstituted 1,4ꢀdienes has been developed through a copperꢀcatalyzed borylꢀallylation of
alkyne with allyl phosphate and bis(pinacolato)diboron. The regioselectivity with respect to the
alkyne and ally phosphate depended on the structures of both the alkyne and allyl phosphates.
For alkynes bearing at least one aryl substituent, the addition of borylcopper to the alkyne mainly
generated a βꢀborylꢀαꢀarylꢀαꢀalkenylcopper species, whose subsequent reaction with secondary
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ally phosphates provided γꢀ(4E)ꢀselective boronꢀsubstituted 1,4ꢀdienes, and with primary allyl
phosphates provided αꢀselective boronꢀsubstituted 1,4ꢀdienes. On the other hand, the αꢀborylꢀαꢀ
arylꢀβꢀalkenylcopper species formed as a minor intermediate from arylalkylacetylene and βꢀ
borylalkenylcopper formed from dialkylacetylene show poor regioselectivity with respect to the
secondary allyl phosphate and produces a mixture of αꢀ and γꢀselective boronꢀsubstituted 1,4ꢀ
dienes. However, their reactions with the primary allyl phosphate are highly γꢀselective. For all
αꢀselective reactions, the configuration of the C=C bond of the allyl phosphate was retained in
the products. The palladiumꢀcatalyzed crossꢀcoupling of boronꢀsubstituted 1,4ꢀdienes and
aromatic, alkenyl, and alkynyl halides gave polyenes or enynes in 68%−95% yields,
demonstrating a versatile building block for the synthesis of 1,4ꢀdienes.
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KEYWORDS: copper catalysis, carboboration, alkyne, allyl phosphate, 1,4ꢀdienylboronate.
1. INTRODUCTION
Organoboron compounds are important reagents in organic chemistry, enabling many chemical
transformations, and the development of efficient strategies for their stereoselective synthesis is
an important goal. Alkenylboronates play an important role in organic synthesis due to their
utility in the Suzuki−Miyaura coupling reaction1 and conjugate additions.2 Metalꢀcatalyzed
borylation of alkynes is the most direct method to access these alkenylboronates. Palladiumꢀ and
nickelꢀcatalyzed carboborations of alkynes have been reported by Suginome et al.3 However, the
use of functionalized alkynes and unusual boron sources in these transformations limits their
application in organic synthesis. In addition, Yoshida et al. have reported a silverꢀcatalyzed
hydroboration of alkynes;4 however, only terminal alkynes were investigated in their work.
Recently, copperꢀcatalyzed borylation of alkynes has emerged as a more general method for the
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synthesis of alkenylboronates. The βꢀborylalkenylcopper species generated from the synꢀaddition
of borylcopper to alkynes are strong carbon nucleophiles and can be reacted with various
electrophiles to form more complex alkenylboronates by the concomitant formation of new C−H,
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C−C, or C−heteroatom bonds (Scheme 1a). It can be protonated by alcohols to produce the
corresponding hydroboration compounds of alkynes.5 Also, the carboboration reaction of alkynes
is becoming an important method for the synthesis of triꢀ and tetrasubsituted alkenlboronates,6
and βꢀborylalkenylcopper can also be captured by CO2 to form cyclic alkenylboronates.7
Furthermore, vicꢀborylstannylalkenes can be obtained by the crossꢀcoupling reaction between βꢀ
borylalkenylcopper and tin alkoxide.8
a. CopperꢀCatalyzed Borylation of Alkynes: Hydroboration,
Carboboration, Boracarboxylation, and Borylstannylation
O
R
R'
O
H
B
B
CO2
ROH
+
Cu B
Hydroboration
Boracarboxylation
R
R'
R
R'
B
Cu
B
R''
B
Sn
Sn OR''
R''X
R
R'
Carboboration
Borylstannylation
R
R'
R
R'
b. This Work: BorylꢀAllylation of Alkynes with Allyl Phosphates:
Synthesis of 1,4ꢀDienylboronates.
R6
R3
—
OPO(OR)2
—
R1
R2
B
Cu
R4
R5
+
R1
R2
Cu
B
R3
R4
—
R4
R6
R3
B
B
—
R5
R5
or
R1
R2
R1
R2
R6 = H, ꢀselective
R6 H, ꢀselective
Scheme 1. Reactions of βꢀBorylalkenylcopper with Electrophiles. (a) Previously Reported
Borylation of Alkynes. (b) This Work.
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The 1,4ꢀdiene framework is a common motif in bioactive natural products.9 Herein, we report
a novel method for the synthesis of boronꢀsubstituted 1,4ꢀdienes through a copperꢀcatalyzed
threeꢀcomponent coupling reaction of bis(pinacolato)diboron, an alkyne, and an allyl phosphate
(Scheme 1b).10 To make the coupling reaction proceed both regioꢀ and stereoselectively is a
challenging task, because there are four possible regioisomers (two for the alkyne if an
unsymmetrical alkyne is used, and two for the allyl phosphate), and more isomers may be
formed if stereoisomers of the double bond are also considered. Other sideꢀreactions include the
hydroboration of the alkyne and boryl substitution of the allyl phosphate.11
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The method reported herein is highly regioꢀ and stereoselective. Furthermore, the boronꢀ
substituted 1,4ꢀdienes can be derivatized to form more complex 1,4ꢀdiene unitꢀcontaining
polyenes with a triꢀ or tetraꢀsubstituted double bond.
2. RESULTS AND DISCUSSION
Condition Optimization and Substrate Scope for the CopperꢀCatalyzed γꢀ(4E)ꢀSelective
Coupling Reaction between a Terminal Alkyne and a Secondary Allyl Phosphate. Different
reaction conditions were screened using phenylacetylene (1ꢀ1), secondary allyl phosphate (Z)ꢀ2ꢀ
1, and diborane 3 as substrates in the presence of a CuCl/ligand catalytic system at 25 °C. As
shown in Table 1, in addition to the desired γꢀ(4E)ꢀselective product [(1E,4E)ꢀ4ꢀ1], αꢀproduct
(1E,4Z)ꢀ5ꢀ1 and the hydroboration product of phenylacetylene [(E)ꢀ6ꢀ1] were also detected by
1H NMR spectra. Ligand screening (Table 1, entries 1–8) shows that (±)ꢀbinap, PCy3, and PPh3
give better combined yields of 4ꢀ1, 5ꢀ1, and 6ꢀ1 (Table 1, entries 4–6, 71%−82%), and higher
selectivities for (1E,4E)ꢀ4ꢀ1 (Table 1, entries 4–6, 91%−94%) when using an ethyl group in the
phosphate moiety.12
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To further improve the yield and selectivity and to suppress the hydroboration reaction, the R
group in the phosphate was optimized using a CuCl/(±)ꢀbinap system (Table 1, entries 9–13). An
excellent yield (95%) and γꢀselectivity (>99%) are obtained when the sꢀbutyl group is present in
the leaving group (Table 1, entry 11). The level of hydroboration product is also suppressed to 3%
in the isolated products. The presence of the larger (2ꢀethyl)hexyl group in the leaving group
results in a slight decrease in the yield (Table 1, entry 12). The presence of the bulky cyclohexyl
group in the leaving group reduces both the yield and selectivity (Table 1, entry 13). The
combination of a leaving group bearing sꢀbutyl in the allyl phosphate with a CuCl/PPh3 or
CuCl/PCy3 catalyst leads to a decrease in both yield and selectivity (Table 1, entries 14 and 15).
The use of (E)ꢀ2ꢀ1 instead of (Z)ꢀ2ꢀ1 as the allyl phosphate also produces (1E,4E)ꢀ4ꢀ1, but with
reduced yield and selectivity (Table 1, entry 16). Interestingly, the reaction proceeds
stereoconvergently with respect to the double bond of the allyl phosphate. Conducting the
reaction in toluene decreases both the yield and selectivity, but increases the hydroboration of
phenylacetylene (Table 1, entry 17). The double bond configuration of 4ꢀ1 was determined to be
(1E,4E) by NOESY analysis (see Supporting Information for details). The reaction is highly
stereoselective for the formation of the (4E) double bond, and the ratio of (1E,4E)ꢀ4ꢀ1 to
(1E,4Z)ꢀ4ꢀ1 is ca. 99:1 under the optimal reaction conditions.
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Table 1. Condition Screening for the Copper(I)ꢀCatalyzed γꢀ(4E)ꢀSelective Synthesis of Boronꢀ
Substituted 1,4ꢀDienes from Terminal Alkynea
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entry
R
ligand
solvent
yield (%)b
4ꢀ1:5ꢀ1c(6ꢀ1%)d
1
Et
dppm
THF
THF
THF
THF
THF
THF
THF
THF
THF
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THF
THF
THF
THF
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toluene
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ꢀ
2
Et
Xantphos
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91:9(6)
3
Et
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Et
(±)ꢀBinap
PCy3
5
Et
6
Et
PPh3
7
Et
P[N(CH3)2]3
95:5(27)
93:7(32)
>99:<1(7)
>99:<1(7)
>99:<1(3)
>99:<1(3)
97:3(2)
8
Et
SIMes⋅HCl
(±)ꢀBinap
(±)ꢀBinap
(±)ꢀBinap
(±)ꢀBinap
(±)ꢀBinap
PPh3
9
nꢀPr
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16e
17
iꢀPr
sꢀBu
2ꢀethylhexyl
Cyclohexyl
sꢀBu
sꢀBu
sꢀBu
sꢀBu
97:3(4)
PCy3
99:1(19)
94:6(14)
99:1(31)
(±)ꢀBinap
(±)ꢀBinap
aReaction conditions: 1ꢀ1 (0.3 mmol), 2ꢀ1 (0.45 mmol), 3 (0.33 mmol), CuCl (0.03 mmol),
ligand, (0.1 equiv for bidentate phosphine or NHC carbene ligand, 0.2 equiv for monodentate
b
phosphine ligand), KOtBu (0.33 mmol), solvent (1.0 ml), 25 °C, 20 h. Cy = cyclohexyl. The
combined isolated yields of 4ꢀ1, 5ꢀ1 and 6ꢀ1. cThe molar ratio of 4 and 5 in the isolated product,
1
determined by H NMR. 4, 5 and 6 can not be separated by silica gel column chromatography.
dThe molar percentage of 6 in the isolated product, determined by 1H NMR spectroscopy. e(E)ꢀ2ꢀ
1 was used, and (1E,4E)ꢀ5ꢀ1 is formed instead of (1E,4Z)ꢀ5ꢀ1.
Using these optimal reaction conditions (Table 1, entry 11), the substrate scope was then
examined using terminal alkynes and a variety of allyl phosphates (Table 2). Phenylacetylene (1ꢀ
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1) was reacted with various allyl phosphates to synthesize corresponding products 4ꢀ2 to 4ꢀ6 in
56%−82% yields with good γꢀ(4E)ꢀselectivities. The terminal allyl phosphate, which exhibits
higher reactivity toward borylcopper catalytic species, affords the desired product (1E,4E)ꢀ4ꢀ4 at
77% yield with >99% γꢀselectivity (4E:4Z = 95:5). The electronic effects of the γꢀBnOCH2 and
γꢀtrimethylsilyl substituents in allyl phosphates do not influence the reactions, and products (E)ꢀ
4ꢀ5 and (1E,4E)ꢀ4ꢀ6 are afforded in 56% and 82% yields, respectively.13 The products resulting
from various terminal aryl alkynes bearing an electronꢀdonating group (EDG) ((1E,4E)ꢀ4ꢀ7 and
(1E,4E)ꢀ4ꢀ8) or an electronꢀwithdrawing group (EWG) at the para ((1E,4E)ꢀ4ꢀ9 to 4ꢀ12), meta
((1E,4E)ꢀ4ꢀ13), and ortho ((1E,4E)ꢀ4ꢀ14) positions are obtained in 43%−83% yields with >99%
γꢀselectivity. It seems that alkynes bearing an EDG give higher concentrations of hydroboration
product 6 (ca. 10%). In addition to the arylacetylenes, an alkenylacetylene can also be utilized to
produce the corresponding product (1E,4E)ꢀ4ꢀ15 in 84% yield with 89% γꢀselectivity. Alkylꢀ
substituted terminal alkynes exhibit poor α/γ regioselectivity and high level of hydroboration
(see Supporting information for details).
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For the terminal alkyne, decreasing the catalyst loading results in a dramatic decrease in yield
((1E,4E)ꢀ4ꢀ3, 5 mol% CuCl, 11% yield; 2 mol% CuCl, 0% yield).
Table 2. Copper(I)ꢀCatalyzed γꢀ(4E)ꢀSelective Synthesis of BoronꢀSubstituted 1,4ꢀDienes from
Terminal Alkynes, Secondary Allyl Phosphates, and Bis(pinacolato)diborona
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75% (>99:<1, 6%)
79% (91:9, 7%); 11%b; 0%c
77% (>99:<1, 2%)
75% (99:1, 10%)
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BnO
Bpin
Ph
(E)-4-5
56% (92:8, 3%)
82% (85:15, 5%)
74% (>99:<1, 9%)
57% (>99:<1, <1%)
77% (>99:<1, <1%)
43% (>99:<1, <1%)
83% (>99:<1, <1%)
64% (>99:<1, <1%)
61% (>99:<1, <1%)
84% (89:11, 3%)
71% (>99:<1, 5%)
aConditions: 1 (0.3 mmol), (Z)ꢀ2 (0.45 mmol), 3 (0.33 mmol), CuCl (0.03 mmol), (±)ꢀbinap
(0.03 mmol), KOtBu (0.33 mmol), THF (1.0 ml), 25 °C, 20 h. The yields are combined isolated
yields of 4, 5 and 6. The molar ratio of 4 and 5, and molar percentage of 6 in the isolated
1
b
product, determined by H NMR spectroscopy, is shown in parentheses. 5 mol% catalyst
loading. c2 mol% catalyst loading.
In all the investigated examples shown in Table 2, <1%–10% (molar percentage)
hydroboration products (6) of the terminal alkynes are present in the isolated products. The
hydroboration products probably result from the protonation of the borylcopperꢀalkyne adducts
by the acidic protons of the terminal alkynes.
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γꢀ(4E)ꢀSelective Coupling Reaction between a Symmetrical Diarylacetylene and a
Secondary Allyl Phosphate. We next explored the borylative alkenyl−allyl coupling reaction
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using symmetrical diarylacetylenes, which have been rarely used in borylative alkenyl−methyl
coupling studies.6c However, under the reaction conditions optimized for the terminal alkynes,
the reaction between diphenylacetylene, (Z)ꢀ2ꢀ1, and 3 affords a complex mixture of γꢀ and αꢀ
selective products (Table 3, entry 1). The γꢀselectivity is greatly improved to 96% when the
reaction is carried out in toluene at 30 °C, though the yield is decreased to 63% (Table 3, entry
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2). Yields of 90%−95% and γꢀselectivity of 99% are achieved when the reaction temperature is
increased to 50−65 °C (Table 3, entries 3 and 4). Further increase in temperature results in a
slight decreases in yield and selectivity (Table 3, entry 5). The CuCl/PPh3 catalytic system is
inferior to the CuCl/(±)ꢀbinap catalytic system in both yield and selectivity (Table 3, entry 3 cf.
entry 6). Again, the use of (E)ꢀ2ꢀ1 instead of (Z)ꢀ2ꢀ1 results in a poor yield (56%) with 94% γꢀ
selectivity (Table 3, entry 7). Under the newly optimized reaction conditions (Table 3, entry 4),
the formation of hydroboration product (Z)ꢀ6ꢀ2 of diphenylacetylene is limited to a nondetectable
level in the 1H NMR spectrum.
Table 3. Reaction Optimization for the Copper(I)ꢀCatalyzed γꢀ(4E)ꢀSelective Synthesis of
BoronꢀSubstituted 1,4ꢀDienes from Symmetrical Diarylacetylenesa
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entry
solvent
THF
ligand
yield (%)b 4ꢀ17:5ꢀ2c(6ꢀ2%)d
temp.(°C)
1
2
3
4
5
6
7e
25
30
50
65
80
50
65
91
63
95
90
87
80
56
48:52(12)
96:4(<1)
99:1(1)
(±)ꢀBinap
(±)ꢀBinap
(±)ꢀBinap
(±)ꢀBinap
(±)ꢀBinap
PPh3
toluene
toluene
toluene
toluene
toluene
toluene
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99:1(<1)
98:2(2)
98:2(2)
94:6(<1)
(±)ꢀBinap
aConditions: 1ꢀ2 (0.3 mmol), (Z)ꢀ2ꢀ1 (0.45 mmol), 3 (0.33 mmol), CuCl (0.03 mmol), (±)ꢀ
binap (0.03 mmol), PPh3 (0.06 mmol), KOtBu (0.33 mmol), solvent (1.0 ml), 25 °C, 20 h. The
combined isolated yields of 4ꢀ17, 5ꢀ2 and 6ꢀ2. The molar ratio of 4ꢀ17 and 5ꢀ2 in the isolated
b
c
1
product, determined by H NMR spectroscopy. 4ꢀ17, 5ꢀ2 and 6ꢀ2 can not be separated by silica
d
gel column chromatography. The molar percentage of 6 in the isolated product, determined by
1H NMR spectroscopy. e(E)ꢀ2ꢀ1 was used instead of (Z)ꢀ2ꢀ1 and (1Z,4E)ꢀ5ꢀ2 is produced instead
of (1Z,4Z)ꢀ5ꢀ2.
Using the optimized reaction conditions (Table 3, entry 4) for internal alkynes,
diphenylacetylene was reacted with various allyl phosphates (Table 4, 4ꢀ18 to 4ꢀ30). In most
syntheses, the γꢀisomeric purity of products 4 is >94%, except for (1Z,4E)ꢀ4ꢀ20 and (Z)ꢀ4ꢀ30,
where 9% and 59% αꢀisomers, respectively, are present in the isolated products. γꢀAlkylꢀ
substituted allyl phosphates give the corresponding products in moderate to good yields (4ꢀ18,
82%; 4ꢀ19, 71%; 4ꢀ20, 74%), whereas poor yields are obtained from terminal allyl phosphate
(Z)ꢀ4ꢀ21 (53%), probably due to its higher reactivity toward borylcopper species at higher
reaction temperatures.14 Interestingly, the presence of a bulky γꢀtertꢀbutyl group in the allyl
phosphate does not hinder the reaction, but gives the desired product (1E,4Z)ꢀ4ꢀ22 in 94% yield
and 99% γꢀselectivity. The electronic effects of γꢀBnOCH2, γꢀTMS, and γꢀphenyl substituents in
the allyl phosphates do not influence the selectivities of the reaction (the γꢀselectivity is 94% for
(Z)ꢀ4ꢀ23, 99% for (1Z,4E)ꢀ4ꢀ24, and 99% for (1Z,4E)ꢀ4ꢀ25). The allyl phosphates bearing bulky
αꢀtertꢀbutyl and αꢀcyclohexyl groups also react smoothly with excellent selectivities ((1Z,4E)ꢀ4ꢀ
26 to 4ꢀ28 show >94% γꢀselectivity). The cyclic allyl phosphate affords the corresponding
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product in excellent yield ((Z)ꢀ4ꢀ29, 91% yield). The diaryl alkynes, symmetrically substituted
with EDGs (paraꢀmethyl or paraꢀmethoxy) or EWGs (paraꢀfluoro or paraꢀtrifluoromethyl),
react with (Z)ꢀ2ꢀ1 to give good yields of the products with an γꢀisomeric purity of >94%
((1Z,4E)ꢀ4ꢀ31 to 4ꢀ34). Unfortunately, the reaction gives a mixture of four isomers, i.e., (γ,4E),
(γ,4Z), (α,4E), and (α,4Z), when a terminal secondary allyl phosphate is used ((1Z,4E)ꢀ4ꢀ35).
In contrast to the terminal alkyne, the catalyst loading can be reduced to as low as 2 mol% for
the synthesis of (1Z, 4E)ꢀ4ꢀ19 using diphenylacetylene (Table 4).
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Table 4. Copper(I)ꢀCatalyzed γꢀ(4E)ꢀSelective Synthesis of BoronꢀSubstituted 1,4ꢀDienes from
Symmetrical Diarylacetylenes, Allyl Phosphates and Bis(pinacolato)diborona
65 °C, 20 h
65 °C, 20 h
82% (99:1)
71% (98:2); 75% (99:1)b;
78% (99:1)c
65 °C, 20 h
74% (91:9)
65 °C, 20 h
80 °C, 20 h
94% (99:1)
65 °C, 20 h
53% (94:6)
53%
80 °C, 20 h
93% (99:1)
50 °C, 16 h
75% (99:1)
65 °C, 20 h
63% (94:6)
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65 °C, 12 h
65 °C, 8 h
65 °C, 20 h
62% (99:1)
73% (99:1)
91%
80 °C, 20 h
83% (41:59)
65 °C, 4 h
65% (99:1)
65 °C, 4 h
80% (98:2)
65 °C, 4 h
89% (94:6)
50 °C, 3 h
82% (98:2)
40 °C, 20 h
44% (37:63)
aConditions: 1 (0.3 mmol), (Z)ꢀ2 (0.45 mmol), 3 (0.33 mmol), CuCl (0.03 mmol), (±)ꢀbinap
(0.03 mmol), KOtBu (0.33 mmol), toluene (1.0 ml). The yields are combined yields of 4 and 5.
1
The molar ratio of 4 and 5 in the isolated product, determined by H NMR spectroscopy, is
shown in parentheses. b5 mol% catalyst loading. c2 mol% catalyst loading.
Reaction of Dialkylacetylene with Allyl Phosphates. Thus far, the alkynes used in the crossꢀ
coupling reaction bear one or two aryl substituents. However, polyenes bearing only alkyl chains
are often found in natural products.15 Therefore, dialkylacetylene was also reacted with
secondary and primary allyl phosphates. The electronꢀrich dibutylacetylene reacts smoothly with
secondary allyl phosphate (Z)ꢀ2ꢀ1 to afford a mixture of two regioisomers (Scheme 2, 7ꢀ1:8ꢀ1 =
31:69).16 In contrast, the reaction of dibutylacetylene with primary allyl phosphate (Z)ꢀ2ꢀ2 in
toluene affords the γꢀselective product (E)ꢀ7ꢀ2 in 41% yield with 99% isomeric purity (Table 5,
entry 1). The reaction carried out in DMF leads to a decrease in regioselectivity (Table 5, entry 2,
7:8 = 88:12).
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Scheme 2. The Reaction of Dibutylacetylene with Allyl Phosphates
Table 5. The Reaction of Dialkylacetylene with Primary Allyl Phosphatesa
entry
R
allyl phosphate
solvent
product
yield (%)b 7:8c
1d
2
Toluene
DMF
41
35
99:1
nꢀBu
(E)ꢀ7ꢀ2
88:12
3
4
Toluene
DMF
19
31
98:2
95:5
nꢀBu
(E)ꢀ7ꢀ3
(E)ꢀ7ꢀ4
5d
6
Toluene
DMF
57
64
99:1
95:5
nꢀBu
nꢀBu
nꢀBu
7
8
Toluene (E)ꢀ7ꢀ4
Toluene (E)ꢀ7ꢀ5
61
51
96:4
95:5
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nꢀBu
DMF
(E)ꢀ7ꢀ6
0
−
6
7
8
9
10
11
Et
Et
(Z)ꢀ2ꢀ4
(E)ꢀ2ꢀ5
Toluene (E)ꢀ7ꢀ7
Toluene (E)ꢀ7ꢀ8
43
35
99:1
98:2
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aConditions: 1 (0.3 mmol), 2 (0.45 mmol), 3 (0.33 mmol), CuCl (0.03 mmol), PCy3 (0.06
mmol), KOtBu (0.33 mmol), solvent (1.0 ml), reaction time (20 h in toluene, 10 h in DMF).
bCombined isolated yields of 7 and 8. cDetermined by 1H NMR spectroscopy. dThe reaction were
carried out at 50 °C.
The presence of a bulky γꢀtertꢀbutyl group in the primary allyl phosphate hinders the reaction
and affords the desired product (E)ꢀ7ꢀ3 in 19% yield and 98% γꢀselectivity (Table 5, entry 3).
Dibutylacetylene reacts with γꢀphenylꢀsubstituted (Z)ꢀ2ꢀ4 and (E)ꢀ2ꢀ4 in toluene to afford (E)ꢀ7ꢀ
4 in 57% yield and 99% γꢀselectivity (Table 5, entry 5), and 61% yield and 96% γꢀselectivity
(Table 5, entry 7), respectively. β,γꢀdisubstituted allyl phosphate (E)ꢀ2ꢀ5 also reacts with
dibutylacetylene to afford (E)ꢀ7ꢀ5 in 51% yield and 95% γꢀselectivity (Table 5, entry 8).
However, γ,γꢀdisubstituted allyl phosphate (E)ꢀ2ꢀ6 does not react with dibutylacetylene (Table 5,
entry 9). The reactions of diethylacetylene with monosubstituted (Z)ꢀ2ꢀ4 and disubstituted (E)ꢀ2ꢀ
5 show similar regioselectivities to those with dibutylacetylene, but result in decreased yields
(Table 5, entries 10 and 11).
γꢀ(4E)ꢀSelective Coupling Reaction between an Arylalkylacetylene and a Secondary Allyl
Phosphate. The addition of borylcopper to unsymmetrical arylalkylacetylenes usually shows
poor regioselectivity.6c Moon’s study17 shows that the relative size of the aryl and alkyl groups
determines the direction when the alkyne is inserted into CuꢀB, with boron adding to the less
bulky side. Indeed, the reaction between (Z)ꢀ2ꢀ1 and phenylpropylacetylene in DMF produces ca.
5% β′ꢀregioisomers (Table 6, entry 1). When the sterically demanding tertꢀbutylphenylacetylene
reacts with (Z)ꢀ2ꢀ1, the regioselectivity for the alkyne is completely inverted,5g and the reaction
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affords the corresponding product (1Z,4E)ꢀβ′γꢀ1 in 64% yield and 99% γꢀisomeric purity (Table
5
6
7
1
6, entry 2).18 No antiꢀaddition products with respect to the alkyne are observed in the H NMR
spectra.5b The reaction of (4ꢀtrifluoromethyl)phenylbutylacetylene with (Z)ꢀ2ꢀ1 also affords 12%
of the β′ꢀregioisomer (Table 6, entry 3), even though there is an EWG on the phenyl ring, which
is expected to direct the copper to the α′ꢀposition by stabilizing the carbon anion during the
insertion reaction. It is interesting to note that the two regioisomers (β′γ and β′α) produced from
the reaction between (αꢀalkyl)alkenylcopper and secondary allyl phosphates show similarly poor
selectivities (Table 6, entry 1, 2% β′γ and 3% β′α; Table 6, entry 3, 6% β′γ and 6% β′α) as the
reaction between dibutylacetylene and secondary allyl phosphate (Scheme 2, 32% γ and 68% α).
It is also important to note that the configuration of the double bond in allyl phosphate (Z)ꢀ2ꢀ1 is
retained in the two αꢀregioisomers ((1Z,4Z)ꢀα′α and (1Z,4Z)ꢀβ′α).
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Further examples show that α′ꢀ and β′ꢀregioselectivities of the products are also strongly
influenced by the structures of the allyl phosphates (Table 6, entries 4 to 9). The β′ꢀregioisomers
produced from the reactions of (4ꢀtrifluoromethyl)phenylbutylacetylene with allyl phosphates
can be limited to a nonꢀdetectable level in the 1H NMR spectrum (Table 6, entries 4 to 9). These
results show that the reaction between alkenylcopper and allyl phosphate is the rateꢀdetermining
step for the complete catalytic cycle, and the higher reactivity of (αꢀaryl)alkenylcopper than (αꢀ
alkyl)alkenylcopper results in the high α′ꢀselectivity.
Table 6. Copper(I)ꢀCatalyzed γꢀ(4E)ꢀSelective Synthesis of BoronꢀSubstituted 1,4ꢀDienes from
Arylalkylacetylenes, Secondary Allyl Phosphates and Bis(pinacolato)diborona
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Entry 1
PPh3, 25 °C, 20 h
60%, (83:12:2:3)
Entry 2
PPh3, 65 °C, 20 h
64%, (0:0:99:1)
Entry 3
PPh3, 25 °C, 20 h
92%, (85:3:6:6)
Entry 4
(±)ꢀBinap, 50 °C, 15 h
89%, (91:9:<1:<1)
Entry 5
±)ꢀBinap, 50 °C, 20 h
82%, (99:1:<1:<1)
Entry 6
(±)ꢀBinap, 50 °C , 20 h
49%, (99:1:<1:<1)
(
Entry 7
(±)ꢀBinap, 50 °C, 20 h
65%, (99:1:<1:<1)
Entry 8
PPh3, 50 °C, 20 h
74%, (99:1:<1:<1)
Entry 9
(±)ꢀBinap, 50 °C, 20 h
93%
aConditions: 1 (0.3 mmol), (Z)ꢀ2 (0.45 mmol), 3 (0.33 mmol), CuCl (0.03 mmol), (±)ꢀbinap
(0.03 mmol), PPh3 (0.06 mmol), KOtBu (0.33 mmol), DMF (1.0 ml). The combined isolated
yields of 4 and 5 are shown in table. The molar ratio of 4 and 5 in the isolated product,
determined by 1H NMR spectroscopy , is shown in parentheses.
αꢀSelective Coupling between an Alkyne and a Primary Allyl Phosphate. All the allyl
phosphates that we tested were formed from secondary allyl alcohols, except for those in (Z)ꢀ4ꢀ
21 and (Z)ꢀ4ꢀ23), and they react with alkynes to produce γꢀEꢀselective boronꢀsubstituted 1,4ꢀ
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dienes. However, preliminary studies showed that reactions using primary allyl phosphates
exhibited reversed regioselectivity, giving primarily αꢀselective products. The reaction
conditions were further screened to improve the αꢀselectivity; the results showed that the
CuCl/PCy3 and CuCl/(±)ꢀbinap catalytic systems in toluene at 50 °C give good results.
Diphenylacetylene was first reacted with primary allyl phosphates of various substitution
patterns (Table 7). αꢀSelective products (1Z,4Z)ꢀ5ꢀ3 and (1Z,4E)ꢀ5ꢀ4 are produced in 68%−71%
yields with >98% αꢀisomeric purity, and the configurations of the double bonds in the allyl
phosphates are completely reserved in the products.19 The allyl phosphate bearing a bulky γꢀ(oꢀ
methyl)phenyl substituent affords (1Z,4Z)ꢀ5ꢀ5 in 51% yield with 99% αꢀisomeric purity. Primary
allyl phosphates bearing γ,γꢀdisubstituents and β,γꢀdisubstituents afford the products in
67%−71% yields with 80%−94% αꢀisomeric purity ((Z)ꢀ5ꢀ6, 90%; (1Z,4E)ꢀ5ꢀ7, 90%; (1Z,4E)ꢀ5ꢀ
8, 94%; (1Z,4E)ꢀ5ꢀ9), 80%). The reactions of primary allyl phosphates with symmetrical
diarylacetylenes bearing EWGs (paraꢀfluoro, paraꢀtrifluoromethyl, and orthoꢀ, metaꢀ, and paraꢀ
chloro) afford αꢀselective products in good yields with >88% αꢀselectivity ((1Z,4E)ꢀ5ꢀ10, 5ꢀ
12−5ꢀ17),20 except for (1Z,4Z)ꢀ5ꢀ11, where the moderate αꢀselectivity (79%) was probably due
to the less hindered γꢀphenyl substituent. The reaction of an unsymmetrical alkyne with primary
allyl phosphates also proceeds smoothly and affords the αꢀselective product in 61%−87% yield
and >90% αꢀselectivity ((1Z,4E)ꢀ5ꢀ18, (Z)ꢀ5ꢀ19, (1Z,4E)ꢀ5ꢀ20 and (1Z,4E)ꢀ5ꢀ21). The results in
Table 7 show that the steric effect of substituents on primary allyl phosphates exerts the main
influence on the regioselectivity of allyl phosphates, with bulky γꢀsubstituents showing good αꢀ
selectivity ((1Z,4E)ꢀ5ꢀ8 cf. (1Z,4E)ꢀ5ꢀ9). Though copperꢀcatalyzed γꢀselective couplings between
a carbon nucleophile and a primary allyl phosphate are common,21 the corresponding αꢀselective
coupling reaction is rare.22
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For the αꢀselective reaction, 2 mol% catalyst loading results in no obvious decrease in yield,
but with a little yet significant improvement in αꢀselectivity (Table 7, (1Z,4E)ꢀ5ꢀ18).
Table 7. αꢀSelective Coupling between an Alkyne and a Primary Allyl Phosphatea
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R1
R4
R3
R5
Bpin
R3
R4
OP(O)(OR6,7,8
)
2
3
CuCl/Ligand,
R2
+
KOtBu
R5
R2
1
toluene, 50 °C
R6 = iPr, R7 = sBu
R8 = 2ꢀethylhexyl
R1
2
5
R7, PCy3, 12 hb
71%, (98:2)
R7, PCy3, 12 hb
68%, (99:1)
R6, PCy3, 4 h
51%, (99:1)
Bpin
Ph
2
Ph
(1Z,4E)-5-7
R7, (±)ꢀBinap, 20 h
R8, PPh3, 12 h
67%, (90:10)
R6, PCy3, 12 h
68%, (94:6)
69%, (90:10)
R6, PCy3, 12 h
71%, (80:20)
R7, (±)ꢀBinap, 4 h
R6, PCy3, 2 h
60%, (79:21)
62%, (99:1)
R7, (±)ꢀBinap, 4 h
R6, PCy3, 3 h
77%, (99:1)
R6, PCy3, 3 h
73%, (88:12)
88%, (93:7)
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R7, PCy3, 3 h
65%, (99:1)
R6, (±)ꢀBinap, 4 h
R6, PCy3, 3 h
76%, (97:3)
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79%, (99:1)
Bpin
Ph
4ꢀCF3C6H4
(1Z,4E)-5-18
Bpin
nꢀBu
4ꢀCF3C6H4
(Z)-5-19
nꢀBu
R6, (±)ꢀBinap, 8 hc
67%, (93:7); 62%,
(99:1)d; 63%, (98:2)e
R7, (±)ꢀBinap, 8 hc
87%, (96:4)
Bpin
Ph
Ph
nꢀPr
(1Z,4E)-5-20
R6, PCy3, 10 h
62%, (94:6)
R6, PCy3, 8 h
61%, (99:1)
aConditions: 1 (0.3 mmol), 2 (0.45 mmol), 3 (0.33 mmol), CuCl (0.03 mmol), (±)ꢀbinap (0.03
mmol), PCy3 (0.06 mmol), KOtBu (0.33 mmol), toluene (1.0 ml), 50 °C. The combined isolated
yields of 5 and 4 are shown in table. The molar ratio of 5 and 4 in the isolated product,
determined by 1H NMR spectroscopy, is shown in parentheses. bThe reactions were carried out at
c
d
e
65 °C. The reactions were carried out in DMF (1.0 ml). 5 mol% catalyst loading. 2 mol%
catalyst loading.
Even though the β′ꢀisomers are produced only in a little amount when phenylpropylacetylene
is reacted with primary allyl phosphate (E)ꢀ2ꢀ5, the high β′γꢀselectivity is interesting (Scheme 3,
5% (Z)ꢀβ′γ, <1% (1Z,4E)ꢀβ′α). It seems that αꢀborylꢀαꢀarylꢀβꢀalkenylcopper species formed as
a minor intermediate from arylalkylacetylene and βꢀborylalkenylcopper formed from
dialkylacetylene show similar regioꢀ and stereoselectivity towards primary and secondary allyl
phosphates.
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Scheme 3. Regioselectivity of βꢀBorylalkenylcopper towards Primary Allyl Phosphate
The Substitutent Effects on the Regioselectivity of γꢀMonoarylꢀSubstituted Primary Allyl
Phosphates. The electronic and steric factors have complicated effects on the regioselectivity of
γꢀmonoarylꢀsubstituted primary allyl phosphates. When diphenyl acetylene (1ꢀ2) were reacted
with γꢀphenylꢀ and γꢀ4ꢀmethoxyꢀphenylꢀsubstituted primary allyl phosphates ((Z)ꢀ2ꢀ4 and (Z)ꢀ2ꢀ
8), the reactions afford corresponding γꢀselective products ((Z)ꢀ4ꢀ36 and (Z)ꢀ4ꢀ37) in good yields
(Scheme 4a and 4b). However, a 2ꢀmethyl substitutent on the γꢀphenyl ring of the allyl
phosphate reversed the regioselectivity (Scheme 4 cf. Table 7, (1Z,4Z)ꢀ5ꢀ5)), indicating that the
regioselectivity of the γꢀmonoarylꢀsubstituted primary allyl phosphates is highly sensitive to the
size of the γꢀsubstitutent. On the other hand, the introduction of substitutens on the phenyl ring of
1ꢀ2 also strongly influences the regioselectivity of (Z)ꢀ2ꢀ4, with EWG groups result in αꢀ
selectivity (Table 7, (1Z,4Z)ꢀ5ꢀ11 and (1Z,4Z)ꢀ5ꢀ14). The alkynes’ substitutents effect on
regioselectivity probably works through the ligand effect of the alkenyl group in βꢀ
borylalkenylcopper intermediate.
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Scheme 4. The Steric and Electronic Effects on Regioselectivity. (a) γꢀSelective Reaction of
(Z)ꢀγꢀphenyl allyl phosphate. (b) γꢀSelective Reaction of (Z)ꢀγꢀ(4ꢀmethoxyphenyl) allyl
phosphate.
Chirality Transfer. The boronꢀsubstituted 1,4ꢀdienenes produced from γꢀsubstituted allyl
phosphates bear a stereogenic center at C3. To obtain optically active product, we investigated
the chirality transfer of an optically active allyl phosphate (Scheme 5). Allyl phosphate (S)ꢀ(Z)ꢀ2ꢀ
7 (96% ee) was reacted with diphenyl acetylene (1ꢀ2) and diboron 3 in the presence of CuCl (0.1
equiv), PPh3 (0.2 equiv), and KOtBu in toluene at 60 °C. (+)ꢀ(1Z,4E)ꢀ4ꢀ19 was obtained at 87%
ee and 88% yield. This result provides a possible route to produce enantiomeric pure boronꢀ
substituted 1,4ꢀdienenes from optically active allyl phosphates. Further work to asymmetrically
synthesize boronꢀsubstituted 1,4ꢀdienenes by chirality transfer and chiral catalyst is in progress.
Scheme 5. Chirality Transfer
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PalladiumꢀCatalyzed CrossꢀCoupling Reactions of BoronꢀSubstituted 1,4ꢀDienes and
Halides. The polyenes and conjugated enynes are an important class of compounds occurring in
a number of natural products and synthetic molecules.23 The coupling reaction of boronꢀ
substituted 1,4ꢀdienes with alkenyl, aryl, and alkynyl halides provides a convenient route to these
compounds. Firstly, the crossꢀcoupling of boronꢀsubstituted 1,4ꢀdienes and halides was carried
out in the presence of Pd(PPh3)4 and NaOH (2.0 equiv) in dioxane (Table 8). Both iodides (9ꢀ1
and 9ꢀ2) and bromides (9ꢀ3 and 9ꢀ4) react with boronꢀsubstituted 1,4ꢀdiene 4 at moderate
temperature (80−100 °C) to form the corresponding coupling products (1E,4E)ꢀ10ꢀ1 to 10ꢀ4 in
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68%−93% yields.24 Interestingly, the sterically demanding aromatic bromide 9ꢀ5 also reacts with
(1E,4E)ꢀ4ꢀ1 efficiently and gives coupling product (1E,4E)ꢀ10ꢀ5 in 91% yield. Secondary
alkenyl bromide 9ꢀ6 reacts with (1E,4E)ꢀ4ꢀ1 to give coupling product (2Z,4E,7E)ꢀ10ꢀ6 in 95%
yield.
The Pd(dba)2/Sphos catalyst system is also effective for the crossꢀcoupling reaction between
boronꢀsubstituted 1,4ꢀdienes 4 and halides. (1E,4E)ꢀ4ꢀ1 reacts with (Z)ꢀ1ꢀbromopropene (9ꢀ7) to
provide triene (2Z,4E,7E)ꢀ10ꢀ7 in 75% yield. Heteroaryl bromide 9ꢀ8 reacts with (1E,4Z)ꢀ4ꢀ17 to
give (1Z,4E)ꢀ10ꢀ8 in 72% yield. Besides the commonly used coupling partners (aryl and alkenyl
halides), 1ꢀbromooctyne (9ꢀ9) also reacts with boronꢀsubstituted 1,4ꢀdiene (1E,4Z)ꢀ4ꢀ17 to form
the conjugated enyne (3E,6E)ꢀ10ꢀ9 in 76% yield.
Table 8. PalladiumꢀCatalyzed CrossꢀCoupling Reactions of BoronꢀSubstituted 1,4ꢀDienes and
Halidesa
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Pd(PPh3)4
80 °C, 81%
Pd(PPh3)4
80 °C, 87%
Pd(PPh3)4,
80 °C, 68%
Pd(PPh3)4
100 °C, 93%
Pd(PPh3)4
100 °C, 91%
Pd(PPh3)4
100 °C, 95%
Pd(dba)2/Sphos
60 °C, 75%
Pd(dba)2/Sphos
100 °C, 72%
Pd(dba)2/Sphos
80 °C, 76%
aConditions: 4 (0.1 mmol), 9 (0.15 mmol, 1.5 equiv), NaOH (2 M aqueous, 100 ꢀL, 0.2 mmol,
2.0 equiv), Pd(PPh3)4 (11.6 mg, 0.01 mmol, 0.1 equiv), Pd(dba)2 (5.8 mg, 0.01 mmol, 0.1 equiv),
Sphos (4.1 mg, 0.01 mmol, 0.1 equiv). Isolated yields of 10 is shown in table
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Mechanistic Consideration. Based on DFT studies by Nakamura et al.,25 the typically
proposed mechanism for the copperꢀcatalyzed coupling reaction between a carbon nucleophile
and an allyl phosphate proceeds via allylic oxidativeꢀaddition and reductive elimination.21d, 21e,
21h, 21i, 26 Sawamura and Ohmiya et al. have also proposed an additionꢀelimination mechanism to
explain the observed high γꢀselectivity.26a, 27 For the γꢀEꢀselective coupling reaction between 1ꢀ2
and (Z)ꢀ2ꢀ1, an addition−elimination mechanism, similar to that proposed by Sawamura and
Ohmiya et al., is proposed (Scheme 4(a)). Firstly, (βꢀboryl)alkenylcopper(I) A, formed from the
synꢀaddition of borylcopper(I) to the alkyne, is added across the C=C bond of (Z)ꢀ2ꢀ1 to form
species B. Species B affords (1E,4Z)ꢀ4ꢀ17 through stereoselective βꢀelimination. The elimination
process may be synꢀ or antiꢀperiplanar, as reported by Tsuji et al.10a
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Scheme 6. Possible Reaction Mechanism. (a) γꢀEꢀSelective Reaction of Secondary Allyl
Phosphates. (b) αꢀSelective Reaction of Primary Allyl Phosphates. (c) The Possible Ligand
Effect of αꢀAlkyl in Alkenylcopper Species on the Regioselectivity of Primary and Secondary
Allyl Phosphates.
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A possible mechanism for the formation of αꢀselective products is shown in Scheme 4(b). Path
“a” is a route similar to that proposed by Hirano and Miura.22 The nucleophilic attack of (βꢀ
boryl)alkenylcopper(I) A on the primary (Z)-allyl phosphate proceeds in an SN2′ manner. The
formed complex C undergoes a rapid σ−π conversion to give the πꢀallyl copper species D. The
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σ−π conversion would need to be much faster than rotation around the σ bond for the
stereochemistry of the starting (Z)ꢀallyl phosphate to be reserved in the product. Reductive
elimination of D at the least hindered carbon center provides (1Z,4Z)ꢀ5ꢀ5.
Path “b” is another possible route. The primary (Z)ꢀallyl phosphate undergoes SN2ꢀtype
oxidativeꢀaddition over the copper center to form E. Subsequent reductive elimination results in
the formation of the αꢀselective product (1Z,4Z)ꢀ5ꢀ5, with the retention of the double bond
configuration.
The study shows that the (αꢀalkyl)alkenylcopper formed from the alkyne (e.g.,
dibutylacetylene) and borylcopper exhibits a different regioselectivity. Its reaction with
secondary allyl phosphates provides a mixture of αꢀ and γꢀselective products (Scheme 2, Table 6,
entries 1 and 3,). However, its reaction with primary allyl phosphates shows high γꢀselectivity
(Table 5 and Scheme 3). This regioselectivity probably results from the electronꢀdonating effect
and small size of the alkyl substituent. A possible mechanism is shown in Scheme 4(c). (αꢀ
Alkyl)alkenylcopper F reacts with (Z)ꢀ2 in an SN2′ manner to form intermediate G, followed by
a rapid σ−π conversion to form πꢀallyl copper species H. The subsequent fast reductive
elimination occurs at the more hindered carbon center. For primary allyl phosphates (i.e., R3 =
H), H eliminates at the γꢀposition and gives γꢀ(E)ꢀproducts J. For secondary allyl phosphates (i.e.,
R3 ≠ H), the elimination occurs at both the γꢀ and αꢀpositions due to their similar steric
environments, and leads to a mixture of the γꢀ(E)ꢀproduct (J) and the αꢀ(Z)ꢀproduct (K).
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It should be noted that the stereo configuration of the C=C bond in allyl phosphates is retained
in all αꢀselective products.
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A synthetic method for the production of a diverse range of boronꢀsubstituted 1,4ꢀdienes through
a copperꢀcatalyzed highly regioꢀ and stereoselective borylꢀallylation of alkynes with allyl
phosphates and bis(pinacolato)diboron is developed and optimized. The system works well with
diverse alkynes, including terminal arylacetylenes, symmetrically diarylꢀsubstituted acetylenes,
symmetrically dialkylꢀsubstituted acetylenes, and arylꢀ and alkylꢀsubstituted acetylenes, and
primary and secondary allyl phosphates with diverse substitutents. The βꢀborylalkenylcopper
species, formed by the synꢀaddition of borylcopper to the alkyne, is the key catalytic species. For
βꢀborylalkenylcopper species with copper adds to the aryl side of alkynes bearing at least one
aryl group, their reactions with secondary allyl phosphates exhibit γꢀ(4E)ꢀselectivity, and their
reactions with primary allyl phosphates exhibit αꢀselectivity. In contrast, for βꢀ
borylalkenylcopper species with copper adds to the alkyl chain side of alkynes, their reactions
with secondary allyl phosphates produce a mixture of αꢀ and γꢀselective products, and their
reactions with primary allyl phosphates show high γꢀselectivity. The regioselectivity of the
unsymmetrically disubstituted acetylene in the products depends on both the intrinsic
regioselectivity when the alkyne is inserted into CuꢀB and the relative reactivity of (1ꢀ
aryl)alkenylcopper and (1ꢀalkyl)alkenylcopper towards allyl phosphates. It seems that the
reaction between alkenylcopper and allyl phosphate is, to some extent, the rateꢀdetermining step.
The boronꢀsubstituted 1,4ꢀdienes are excellent reactants in the palladiumꢀcatalyzed Suzukiꢀ
Miyaura crossꢀcoupling reaction, demonstrating a versatile building block for the synthesis of
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1,4ꢀdienes. Further experimental study using chiral catalysts and enantiomeric pure allyl
phosphates are in progress.
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1
Details of synthetic procedures and characterization of compounds by HꢀNMR, 13CꢀNMR,
NOESY, and HRMS. This material is available free of charge via the Internet at
http://pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
* Eꢀmail: zhongcm@nwsuaf.edu.cn.
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENT
This work was supported by the Foundation of Northwest A&F University (No. Z111021007),
the Natural Science Foundation of Heilongjiang Province of China (No. B200604), the Scientific
Research Foundation for Returned Scholars, Ministry of Education of China, the Science and
Technology Innovation Program of Harbin Science and Technology Bureau for Returned
Scholars (No. 2007RFLXG016), and the Foundation of Harbin Normal University (No.
KG2007−05). The authors greatly appreciate AllyChem Corporation Limited (Dalian, China) for
the kind provision of bis(pinacolato)diboron. We thank Prof. H.ꢀL. Zhang for his expert
assistance in NOESY data collection.
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