Diastereo- and Enantioselective Synthesis of (E)-δ-Boryl-Substituted anti-Homoallylic Alcohols in Two Steps from Terminal Alkynes

Article abstract of DOI:10.1002/anie.201908299

We report the highly diastereo- and enantioselective preparation of (E)-δ-boryl-substituted anti-homoallylic alcohols in two steps from terminal alkynes. This method consists of a cobalt(II)-catalyzed 1,1-diboration reaction of terminal alkynes with B₂pin₂ and a palladium(I)-mediated asymmetric allylation reaction of the resulting 1,1-di(boryl)alk-1-enes with aldehydes in the presence of a chiral phosphoric acid. Propyne, which is produced as the byproduct during petroleum refining, could be used as the starting material to construct homoallylic alcohols that are otherwise difficult to synthesize with high stereocontrol.

Full text of DOI:10.1002/anie.201908299

A Journal of the Gesellschaft Deutscher Chemiker
Angewandte
Chemie
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Accepted Article
Title: Diastereo- and Enantioselective Synthesis of (E)-δ-Boryl-
Substituted anti-Homoallylic Alcohols in Two Steps from Terminal
Alkynes
Authors: Tomoya Miura, Naoki Oku, and Masahiro Murakami
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To be cited as: Angew. Chem. Int. Ed. 10.1002/anie.201908299
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10.1002/anie.201908299
Angewandte Chemie International Edition
COMMUNICATION
d
Diastereo- and Enantioselective Synthesis of (E)- -Boryl-
Substituted anti-Homoallylic Alcohols in Two Steps from
Terminal Alkynes
Tomoya Miura,* Naoki Oku, and Masahiro Murakami*
Dedicated to Professor Amir Hoveyda on the occasion of his 60th birthday
Abstract: Herein we report the highly diastereo- and
enantioselective preparation of (E)-d-boryl-substituted anti-
homoallylic alcohols in two steps from terminal alkynes. Namely, it
consists of a cobalt(II)-catalyzed 1,1-diboration reaction of terminal
di(boryl)alk-1-enes, there is an excellent preparative method
available; 1,1-diboration of terminal alkynes has been realized
by combined use of cobalt(II) catalyst and
a
a
bis(pinacolato)diboron (B2pin2).[12] We now report a diastereo-
and enantioselective synthesis of (E)-d-boryl-substituted anti-
homoallylic alcohols in two steps starting from terminal alkynes
[Figure 1(b)]. Since the accessibility of starting materials and
reagents is one of the most important criteria for a synthetic
reaction to be useful, it is of note that allylic boron species, the
key reactive intermediates in this protocol are generated from
terminal alkynes that are among the most readily accessible,
even from commercial sources.
alkynes with B2pin2 and
a palladium(I)-mediated asymmetric
allylation reaction of the resulting 1,1-di(boryl)alk-1-enes with
aldehydes in the presence of a chiral phosphoric acid. Propyne,
which is produced as the byproduct during petroleum refining, could
be used as the starting material to construct highly stereocontrolled
homoallylic alcohols that are otherwise difficult to synthesize.
Homoallylic alcohols are commonly used building blocks for the
synthesis of polyketide natural products and pharmaceuticals.[1]
The allylation reaction of aldehydes with allylic boron reagents
provides one of the most reliable methods for the
stereoselective synthesis of homoallylic alcohols.[2] Recently, an
enantioselective allylation reaction using allylic boron reagents
functionalized with another metalloid element, such as tin,
silicon, and boron, has attracted much attention.[3-6]
Advantageously in these cases the metalloid elements
remaining in the products lead to a variety of further synthetic
transformations. Roush and co-workers have developed a
unique method for generating in situ (S)-a-stannyl allylic boron
species from allenylstannane and (–)-diisopinocamphenyl-
borane [(dIpc)2BH] through hydroboration/1,3-boratropic shift.[7]
The following allylation reaction of aldehydes affords (E)-d-
a) Roush[7]
stoichiometric
(dIpc)2BH
Sn
OH
*
PhCHO
–78 °C
*
Sn
B(dIpc)2
Ph
Sn
(S)
93% ee
Sn = Bu3Sn
b) This work
Me
PhCHO
catalytic
[PdI]2, PA*
catalytic
[CoII]
Bpin
Bpin
OH
Me
Bpin
B2pin2
20 °C
Ph
*
95% ee
Figure 1. Enantioselective synthesis of (E)-d-metalloid-substituted homoallylic
alcohols. (a) d-Stannyl group. (b) d-Boryl group. dIpc = d-isopinocamphenyl. pin =
pinacolato. PA* = chiral phosphoric acid.
Initially, 1,1-di(pinacolatoboryl)prop-1-ene (3a) was prepared
from propyne (1a) under slightly modified conditions of those
which were originally reported by Chirik and co-workers [Eq.
(1)];[12] a THF solution of 1a (ca. 1.0 M), B2pin2 (2, 1.0 equiv),
and cobalt(II) catalyst (4.0 mol %) was stirred at room
temperature for 24 h. Chromatographic purification on silica gel
gave 3a in 85% isolated yield. Alternatively, 3a could be
prepared also by a carboxylic acid-catalyzed hydroboration of 1-
(pinacolatoboryl)propyne with pinacolborane (HBpin)[13] (see
Supporting Information).
stannyl-substituted
homoallylic
alcohols
with
high
enantioselectivities [Figure 1(a)]. On the other hand, we have
developed convenient methods for generating in situ allylic
boron species from precursory (alkenyl)boron compounds
through a transition-metal catalyzed double-bond transposition
reaction.[8-10] The generated allylic boron species immediately
adds to aldehydes, where a high enantioselectivity is induced by
the
chiral
phosphoric
acid.[11]
Homoallylic
alcohols,
functionalized with silicon and boron at the g and d positions,
can be synthesized from 1-boryl-2-silylalk-1-enes,[8a] 1,2-
di(boryl)alk-1-enes,[8d] and 1,1-di(boryl)alk-3-enes[8b,c]. We next
examined the use of 1,1-di(boryl)alk-1-enes as the precursory
(alkenyl)boron compounds, which would give rise to d-boryl-
substituted homoallylic alcohols. For the precursory 1,1-
Me
Cy
N
Me
N
Co
Me
N
Bpin
(4.0 mol %)
Cy
Me
(1)
+
Me
B2pin2
Bpin
3a 85%
THF, RT, 24 h
1a
2
(1.0 equiv)
[*]
Dr. T. Miura, N. Oku, Prof. Dr. M. Murakami
Department of Synthetic Chemistry and Biological Chemistry
Kyoto University, Katsura, Kyoto 615-8510 (Japan)
E-mail: tmiura@sbchem.kyoto-u.ac.jp
Next, catalysts for the double-bond transposition reaction
were examined in an allylation reaction of benzaldehyde (4a)
murakami@sbchem.kyoto-u.ac.jp
with the isolated 3a. Whereas no reaction was observed with
Supporting information and the ORCID identification number(s) for
the author(s) of this article can be found under:
https://doi.org/10.1002/anie201908299.
[14]
iridium(I) complex [IrCl(coe)2]2/PCy3/NaBPh4
and cationic
ruthenium(II) complex [Ru(L)]PF6 (Grotjahn catalyst),[15] the
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10.1002/anie.201908299
Angewandte Chemie International Edition
COMMUNICATION
palladium(I) dimer [Pd(µ-Br)(Pt-Bu3)]2, which was developed by
Gooßen and co-workers,[16] proved to be active for the double-
bond transposition of 3a; a mixture of 4a, 3a (2.0 equiv), [Pd(µ-
Br)(Pt-Bu3)]2 (7.5 mol %), and 4 Å molecular sieves (4 Å M.S.) in
1,2-dichloroethane (DCE)/toluene (1:1, 0.2 M) was stirred at
20 °C [Eq. (2)]. After 2 h, an aliquot of the reaction mixture was
thermodynamically more stable isomer, which is catalyzed by
palladium.
‡
Me
Me
Me
Me
H
O
B
OBpin
Ph
H
O
O
H
1
Ph
analyzed by H NMR, which suggested that d-boryl-substituted
Bpin
H
B
homoallylic alcohol 5aa was produced in 11% NMR yield with
an E/Z ratio = 39:61. After 17 h, 5aa was formed in 43% yield
with an E/Z ratio = 95:5.[17] Thus, the (Z)-isomer was initially
(Z)-5aa'
O
O
PhCHO
A1,3
strain
4a
cat.
[PdI]2
+
TS A
produced
and
gradually
isomerized
to
the
more
‡
Bpin
Me
Me
thermodynamically stable (E)-isomer.
Bpin
6a
Me
Me
O
OBpin
H
O
Bpin
B
[Pd(µ-Br)(Pt-Bu3)]2
Ph
H
O
O
Ph
B
Bpin
(7.5 mol %)
OH
O
gauche
int.
(E)-5aa'
Me
(2)
PhCHO
+
H
H
Bpin
Bpin
3a
(2.0 equiv)
Ph
DCE/toluene
4a
TS B
5aa
4 Å M.S., 20 °C
Scheme 1. Proposed pathway for the formation of (E)-5aa’ from 4a and 6a.
Time Yield [%] E/Z
2 h
11%
43%
39:61
95:5
Next, we examined the palladium(I)-catalyzed allylation
reaction of 4a with 3a in the presence of a catalytic amount (5.0
mol %) of chiral phosphoric acid (R)-TRIP.[19] The reaction
proceeded more rapidly at 20 °C, and after 17 h, 4a was
thoroughly consumed even with 5.0 mol % of [Pd(µ-Br)(Pt-Bu3)]2.
d-Boryl-substituted homoallylic alcohol 5aa was isolated in 84%
yield with an E/Z ratio over 95:5 [Eq. (4)]. Moreover, a high level
of enantioselectivity (95% ee) was observed with (E)-5aa.[20]
This reaction provides a stereoselective pathway from propyne
and benzaldehyde to the product with a significant increase of
structural complexity. Propyne gas is produced as the byproduct
during petroleum refining,[21] and this abundant feedstock is an
ideal C3 source for fine synthetic chemistry.[22]
17 h
It is assumed that monomeric complex [Pd(Pt-Bu3)(H)(Br)]
generated in situ from [Pd(µ-Br)(Pt-Bu3)]2 catalyzes double-bond
transposition of 1,1-di(pinacolatoboryl)prop-1-ene (3a) leading
to
1,1-di(pinacolatoboryl)prop-2-ene
(6a)
through
an
addition/elimination mechanism.[16] In order to confirm the
double-bond transposition process, the reaction was monitored
by 1H NMR spectroscopy in the absence of the aldehyde 4a [Eq.
(3)]. Only a trace amount of 6a was formed after 17 h and 3a
was recovered almost quantitatively, suggesting that 1,1-
di(pinacolatoboryl)prop-2-ene 6a is thermodynamically less
stable than 1,1-di(pinacolatoboryl)-prop-1-ene (3a).[18] It is
proposed the very small amounts of 6a generated from 3a
reacts immediately with the aldehyde 4a to afford the
homoallylic alcohol 5aa.
[PdI]2 (5.0 mol %)
iPr
iPr
[PdI]2 (5.0 mol %)
Bpin
Bpin
iPr
O
Me
+
3a
(3)
O
Bpin
3a
Bpin
6a
P
DCE/toluene
O
iPr
OH
4 Å M.S., 28 ºC
Time
17 h
3a/6a
99:1
PhCHO
iPr
iPr
On the basis of the results of the experiments mentioned
above and the previous studies on the allylation reaction with
1,1-di(pinacolatoboryl)but-2-ene,[8b,c] we propose that the (Z)-
isomer of 5aa is initially formed from 4a and 6a through a six-
membered chairlike transition state depicted in Scheme 1. One
of the two boryl groups takes either a pseudo-axial position (TS
A) leading to the (Z)-isomer or a pseudo-equatorial position (TS
B) leading to the (E)-isomer. TS A exhibits 1,3-allylic strain
interactions between the boryl group located in a pseudo-axial
position and a hydrogen atom, whereas the boryl group located
in a pseudo-equatorial position in TS B suffers from gauche
influence with the pinacolato ligand of the other boryl group. The
gauche interaction in TS B is more significant than the 1,3-allylic
strain in TS A, and thus, the TS A is favored over the TS B,
leading to the formation of the (Z)-isomer. The selective
4a
(R)-TRIP (5.0 mol %)
OH
+
(4)
Bpin
Bpin
Ph
DCE/toluene
Me
5aa 84%, 95% ee (R)
E/Z >95:5
4 Å M.S., 20 °C, 17 h
Bpin
3a
(2.0 equiv)
The two-step protocol found a wide scope in both terminal
alkynes and aldehydes. Besides propyne (1a), a variety of
longer terminal alkynes (R2-CH2C≡CH) were readily transformed
to 1,1-di(boryl)alk-1-enes 3b–3f by the Co(II)-catalyzed 1,1-
diboration with B2pin2[12] or through the carboxylic acid-catalyzed
hydroboration of 1-(boryl)alk-1-ynes with HBpin.[13] Compounds
3b–3f were subjected to the asymmetric allylboration of
benzaldehyde (4a) (Table 1). The presence of the R2
substituents raised another stereochemical issue, and excellent
anti-selectivity over 95:5 was observed in each case. The
production of the (E)-isomer is
a result of geometrical
isomerization of the initially-formed (Z)-isomer to the
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10.1002/anie.201908299
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COMMUNICATION
Me
+
Bpin
Bpin
reaction of 1,1-di(pinacolatoboryl)but-1-ene (3b) proceeded
most efficiently to give the b-methyl-d-boryl-substituted
homoallylic alcohol 5ab in 92% yield with 98% ee, even with 1.0
mol % of [Pd(µ-Br)(Pt-Bu3)]2 (entry 1). Thus, this two-step
protocol works well not only for allylation but also for crotylation
of aldehydes. 1,1-Di(pinacolatoboryl)pent-1-ene (3c) and 1,1-
di(pinacolatoboryl)-4-methylpent-1-ene (3d) were also suitable
reagents to install ethyl and isopropyl substituents as R2 with
high enantioselectivities (entries 2 and 3). On the other hand, an
enantioselectivity of 72% ee was observed with 3e having a
phenyl substituent (entry 4). The b-oxy-substituted homoallylic
alcohol 5af was also obtained in 85% yield with 82% ee (entry
5). Notably, a boryl group remained in the products unaffected
by the palladium catalyst in all cases.
[PdI]2
Bpin
(1.0 mol %)
(E)-7
Me
Bpin
Bpin
+
(5)
3b
Bpin
Bpin
DCE/toluene
8
3b
4 Å M.S., 20 ºC
Me Bpin
(Z)-7
Time 3b/(E)-7/(Z)-7/8 E/Z (7)
10 min
59:36:4:<1 89:11
A wide scope of aldehydes were used in the asymmetric
allylation reaction with 1,1-di(pinacolatoboryl)prop-1-ene (3a)
(Table 2). d-Boryl-substituted homoallylic alcohols 5aa–5ea
were obtained in good to high yields from an electronically and
sterically diverse array of aromatic aldehydes 4a–4e (entries 1–
5). High E/Z ratios over 95:5 and enantioselectivities ranging
from 91% to 95% ee were observed. Heteroaromatic aldehyde
4f and a,b-unsaturated aldehyde 4g were also applicable in this
reaction (entries 6 and 7). Aliphatic aldehydes such as 3-
phenylpropanal (4h), nonanal (4i), and cyclohexane-
carbaldehyde (4j) participated in the reaction, although the
enantioselectivities were slightly lower at 86–91% ee (entries 8–
10). When hex-5-enal was employed, the terminal double bond
also underwent transposition to give an isomeric mixture.
Table 1: Enantioselective allylation reactions of 4a with various 1,1-
di(boryl)alk-1-enes 3b–3f.[a]
OH
[PdI]2, (R)-TRIP
Bpin
R2
Bpin
+
PhCHO
Ph
DCE/toluene
Bpin
3 (2.0 equiv)
4a
R2
5
4 Å M.S., 20 °C
En
try
R2 (3)
[PdI]2
(R)- Time
5
Yield anti/s
[%][b]
E/Z[c]
ee
[%][d]
TRIP
[mol
%]
yn[c]
[mol %
]
[h]
Table 2: Enantioselective allylation reactions of various aldehydes 4a–4j with
3a.[a]
1
Me
(3b)
1.0
5.0
8
5ab
5ac
92
91
>95:5 >95:5
>95:5 >95:5
98
2
3
Et (3c)
2.5
5.0
5.0
10
8
95
90
Bpin [PdI]2, (R)-TRIP
OH
R1CHO
Me
5ad 67[e] >95:5
95:5
+
iPr
36
Bpin
R1
Bpin
3a (2.0 equiv)
DCE/toluene
4
(3d)
4 Å M.S., 20 °C
5
4
5
Ph
(3e)
7.5
7.5
7.5
10
36
36
5ae
5af
86
85
>95:5 >95:5
>95:5 >95:5
72
82
En
try
R1 (4)
[PdI]2
(R)-
Time
[h]
5
Yield
[%][b]
E/Z[c]
ee
[%][d]
TRIP
[mol
%]
[mol %
]
(MOM)
O (3f)
[a] On a 0.20 mmol scale. [b] Yields of E/Z mixtures after chromatographic
purification (average of two runs). [c] Ratios determined by 1H NMR. [d] The
1
2
Ph (4a)
5.0
5.0
5.0[e]
17
17
5aa
5ba
87
80
>95:5
>95:5
95
91
4-ClC6H4
(4b)
5.0
ee values of (E)-5 determined by chiral HPLC. [e] 40 °C. MOM
=
methoxymethyl.
3
4
5
4-MeOC6H4
7.5
5.0
5.0
10
5.0
5.0
36
17
17
5ca
5da
5ea
78
82
84
>95:5
>95:5
>95:5
91
95
94
(4c)
The process of double-bond transposition of 1,1-
di(pinacolatoboryl)but-1-ene (3b) was also monitored by 1H
NMR spectroscopy, in the absence of the aldehyde 4a [Eq. (5)].
When 3b was treated with 1.0 mol % of [Pd(µ-Br)(Pt-Bu3)]2 in
DCE/toluene at 20 °C, double-bond transposition took place
promptly, and after 10 min, gave a mixture of 3b/(E)-7/(Z)-7/8 =
59:36:4:<1. After 17 h, it made an equilibrium mixture of 3b/(E)-
7/(Z)-7/8 = 43:38:18:<1.[23] This behavior contrasted with that of
1,1-di(pinacolatoboryl)prop-1-ene (3a) shown in Eq. (3). It is
likely that the thermodynamic stabilities of the allylic boron
species (E)-7 and (Z)-7 are increased because of vicinally
disubstituted alkenes.[24] The E/Z ratio of 7 was 89:11. As we
have previously reported,[8b] (E)-7 reacts with benzaldehyde (4a)
faster than (Z)-7. This seems to be the reason of the
enhancement of the E/Z ratio up to the anti/syn ratio observed
with 5ab (>95:5).
4-MeC6H4
(4d)
2-MeC6H4
(4e)
6
7
2-furyl (4f)
7.5
7.5
10
36
36
5fa
68
71
95:5
93:7
93
91
PhCH=CH
7.5
5ga
(4g)
8
PhCH2CH2
7.5
10
36
5ha
83
92:8
88
(4h)
9
C8H17 (4i)
Cy (4j)
7.5
5.0
10
36
17
5ia
5ja
84
77
95:5
86
91
10
7.5
>95:5
[a] On a 0.20 mmol scale. [b] Yields of E/Z mixtures after chromatographic
purification (average of two runs). [c] Ratios determined by 1H NMR. [d] The
ee values of (E)-5 determined by chiral HPLC. [e] (S)-TRIP was used.
It was possible to apply the product 5aa directly to a Suzuki-
Miyaura cross-coupling reaction (Scheme 2);[25] after the
allylation reaction, bromobenzene, KOH, and H2O were added
directly to the reaction mixture containing 5aa. After 3 h,
aqueous workup and chromatographic purification on silica gel
gave the phenylated product 9 in 77% yield with 94% ee. An
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10.1002/anie.201908299
Angewandte Chemie International Edition
COMMUNICATION
products is suitable for subsequent synthetic derivatizations
including carbon–carbon bond formation.
analogous sequential procedure using ethyl (Z)-3-iodoacrylate
also afforded the conjugated ester 10.
PhBr
OH
(4.5 equiv)
Acknowledgements
Ph
Ph
KOH, H2O
DCE/toluene
28 °C, 3 h
9 77%, 94% ee
E/Z = >95:5
This work was supported by MEXT [Grants-in-Aids for Scientific
Research (S) (15H05756)] and ISHIZUE 2019 of Kyoto
University Research Development Program. We thank Mr. J.
Nakahashi (Kyoto Univ.) for his contribution at a preliminary
stage.
[PdI]2 (5.0 mol %)
PhCHO
4a
(R)-TRIP (5.0 mol%)
+
Bpin
DCE/toluene
20 °C, 17 h
Me
I
Bpin
CO2Et
OH
3a
(4.3 equiv)
Ph
Keywords: allylation • asymmetric synthesis • double-bond
(2.0 equiv)
KOH, H2O
DCE/toluene
40 °C, 8 h
CO2Et
transposition • homoallylic compounds • palladium
10 73%, 95% ee
E/Z = 90:10
[1]
[2]
M. Yus, J. C. González-Gómez, F. Foubelo, Chem. Rev. 2013, 113,
5595.
Scheme 2. Suzuki-Miyaura cross-coupling by a one-pot sequence.
a) D. G. Hall, H. Lachance, Allylboration of Carbonyl Compounds,
Wiley, Hoboken, New Jersey, 2012. See also: b) J. Feng, Z. A. Kasun,
M. J. Krische, J. Am. Chem. Soc. 2016, 138, 5467.
The boryl group remaining in the homoallylic alcohols could
be exploited for various synthetic transformations other than a
cross-coupling reaction (Scheme 3). Treatment of 5aa with an
excess amount (4.0 equiv) of CuCl2 resulted in the formation of
alkenyl chloride 11 with its geometrical integrity maintained (E/Z
>95:5).[26] TBS protection of the hydroxy group of 5aa[27]
followed by oxidation of the B–C bond with NaBO3 afforded g-
siloxy aldehyde 12, which is a common intermediate for the
synthesis of pyrrolidine sedum alkaloids, (–)-pyrrolsedamine
and (+)-pyrrolallosedamine.[28] (–)-g-Dodecalactone 13, originally
isolated from rove beetles as a defensive secretion, was
stereoselectively synthesized from 5ia through sequential
double oxidation with NaBO3 and PCC.[29]
[3]
[4]
For a recent review on chiral allylic boron reagents, see: C. Diner, K. J.
Szabó, J. Am. Chem. Soc. 2017, 139, 2.
For enantioselective synthesis of b-metalloid-substituted homoallylic
alcohols, see: [B] a) M. Chen, W. R. Roush, J. Am. Chem. Soc. 2013,
135, 9512; [Si] b) M. Binanzer, G. Y. Fang, V. K. Aggarwal, Angew.
Chem. Int. Ed. 2010, 49, 4264; Angew. Chem. 2010, 122, 4360; c) M.
Chen, W. R. Roush, Org. Lett. 2011, 13, 1992; d) P. Barrio, E.
Rodríguez, K. Saito, S. Fustero, T. Akiyama, Chem. Commun. 2015,
51, 5246.
[5]
[6]
For enantioselective synthesis of d-metalloid-substituted homoallylic
alcohols, see: [Si] a) M. Chen, W. R. Roush, Org. Lett. 2013, 15, 1662;
[Sn] b) M. Chen, W. R. Roush, J. Am. Chem. Soc. 2011, 133, 5744.
For recent other examples, see: a) F. Peng, D. G. Hall, J. Am. Chem.
Soc. 2007, 129, 3070; b) G. E. Ferris, K. Hong, I. A. Roundtree, J. P.
Morken, J. Am. Chem. Soc. 2013, 135, 2501; c) T. S. N. Zhao, J. Zhao,
K. J. Szabó, Org. Lett. 2015, 17, 2290; d) J. Zhao, K. J. Szabó, Angew.
Chem. Int. Ed. 2016, 55,1502; Angew. Chem. 2016, 128, 1524; e) L.
Mao, R. Bertermann, K. Emmert, K. J. Szabó, T. B. Marder, Org. Lett.
2017, 19, 6586; f) M. Wang, S. Gao, M. Chen, Org. Lett. 2019, 21,
2151.
CuCl2
OH
OH
Bpin
Cl
Ph
Ph
MeOH/H2O
5aa
11 86%, 95% ee
E/Z >95:5
i) TBSCl
imidazole
Me
OH
ref. 28
OTBS
Ph
5aa[27]
N
[7]
[8]
M. Chen, D. H. Ess, W. R. Roush, J. Am. Chem. Soc. 2010, 132, 7881.
a) T. Miura, Y. Nishida, M. Murakami, J. Am. Chem. Soc. 2014, 136,
6223; b) T. Miura, J. Nakahashi, M. Murakami, Angew. Chem. Int. Ed.
2017, 56, 6989; Angew. Chem. 2017, 129, 7093; c) T. Miura, J.
Nakahashi, W. Zhou, Y. Shiratori, S. G. Stewart, M. Murakami, J. Am.
Chem. Soc. 2017, 139, 10903; d) T. Miura, J. Nakahashi, T. Sasatsu,
M. Murakami, Angew. Chem. Int. Ed. 2019, 58, 1138; Angew. Chem.
2019, 131, 1150.
CHO
ii) NaBO3
Ph
12 71% (2 steps)
(+)-pyrrolallosedamine
96% ee
OH
O
OH
i) NaBO3
ii) PCC
O
O
Bpin
C8H17
[9]
For related reactions involving double-bond transposition of precursory
(alkenyl)boron compounds, see: a) Y. Yamamoto, T. Miyairi, T.
Ohmura, N. Miyaura, J. Org. Chem. 1999, 64, 296; b) L. Lin, K.
Yamamoto, S. Matsunaga, M. Kanai, Angew. Chem. Int. Ed. 2012, 51,
10275; Angew. Chem. 2012, 124, 10421; c) R. Hemelaere, F.
Carreaux, B. Carboni, Chem. Eur. J. 2014, 20, 14518; d) F. Weber, M.
Ballmann, C. Kohlmeyer, G. Hilt, Org. Lett. 2016, 18, 548; e) B. M.
Trost, J. J. Cregg, N. Quach, J. Am. Chem. Soc. 2017, 139, 5133; f) J.
Park, S. Choi, Y. Lee, S. H. Cho, Org. Lett. 2017, 19, 4054; g) S. Gao,
J. Chen, M. Chen, Chem. Sci. 2019, 10, 3637.
5ia
C8H17
C8H17
13 53% (2 steps)
84% ee
(–)-γ-Dodecalactone
Scheme 3. Synthetic transformations of d-boryl-substituted homoallylic
alcohols. PCC = pyridinium chlorochromate.
In summary, we have developed an efficient method for the
diastereo- and enantioselective synthesis of (E)-d-boryl-
substituted anti-homoallylic alcohols via 1,1-di(boryl)alk-1-enes
from terminal alkynes. The use of terminal alkynes as the
starting materials is a key advantage to our method, presenting
better chances of application to synthetic enterprises.
Furthermore, the alkenylboronic ester element remaining in the
[10] For
a recent review on tandem processes involving double-bond
transposition, see: a) H. Sommer, F. Juliá-Hernández, R. Martin, I.
Marek, ACS Cent. Sci. 2018, 4, 153. For a recent example, see: b) H.
Sommer, T. Weissbrod, I. Marek, ACS Catal. 2019, 9, 2400.
[11] P. Jain, J. C. Antilla, J. Am. Chem. Soc. 2010, 132, 11884.
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10.1002/anie.201908299
Angewandte Chemie International Edition
COMMUNICATION
[12] S. Krautwald, M. J. Bezdek, P. J. Chirik, J. Am. Chem. Soc. 2017, 139,
3868.
[20] The absolute configuration of 5aa was assigned as R based on the
optical rotation of the phenylated product 9. See: S. Teng, M. E.
Tessensohn, R. D. Webster, J. S. Zhou, ACS Catal. 2018, 8, 7439. The
absolute configurations of the other products were assigned by analogy.
[21] In cracking process, propyne gas constitutes 0.3–0.8 mass percent
(wt %) of million-metric-ton scale per year. See: K. Buckl, A.
Meiswinkel, Propyne. Ullmann’s Encyclopedia of Industrial Chemistry,
Wiley-VCH, Weinheim, 2008.
[13] H. E. Ho, N. Asao, Y. Yamamoto, T. Jin, Org. Lett. 2014, 16, 4670.
[14] S. G. Nelson, C. J. Bungard, K. Wang, J. Am. Chem. Soc. 2003, 125,
13000.
[15] D. B. Grotjahn, C. R. Larsen, J. L. Gustafson, R. Nair, A. Sharma, J.
Am. Chem. Soc. 2007, 129, 9592.
[16] P. Mamone, M. F. Grünberg, A. Fromm, B. A. Khan, L. J. Gooßen, Org.
Lett. 2012, 14, 3716.
[22] a) T. Luong, S. Chen, K. Qu, E. L. McInturff, M. J. Krische, Org. Lett.
2017, 19, 966. See also: b) R. Y. Liu, Y. Zhou, Y. Yang, S. L. Buchwald,
J. Am. Chem. Soc. 2019, 141, 2251 and references therein.
[23] A mixture of an essentially same composition resulted when 8 was
subjected to the identical conditions for double-bond transposition.
[24] DFT calculation [B3LYP/6-31G(d)] showed that (E)-7 and (Z)-7 are less
stable than 3b by 1.5 and 2.2 kcal/mol, respectively.
[17] During aqueous workup, the (Z)-isomer of 5aa cyclized to cyclic
boronic ester 14.[8c] Therefore, what we isolated was a 95:5 mixture of
(E)-5aa/14. Other E/Z ratios were determined similarly.
OH
B
O
[25] F. Proutiere, M. Aufiero, F. Schoenebeck, J. Am. Chem. Soc. 2012,
134, 606.
Ph
14
[18] DFT calculation [B3LYP/6-31G(d)] showed that 6a is less stable than
3a by 5.4 kcal/mol. The p-electrons of the double bond of 3a delocalize
into the vacant p orbitals on the two boron atoms to electronically
stabilize 3a. The two sterically demanding boryl groups of 3a are bound
to the sp2 carbon having wider bond angles (120°) than sp3 carbons to
sterically favor 3a.
[26] J. M. Murphy, X. Liao, J. F. Hartwig, J. Am. Chem. Soc. 2007, 129,
15434.
[27] It was prepared by the use of (S)-TRIP.
[28] V. A. Bhosale, S. B. Markad, S. B. Waghmode, Tetrahedron 2017, 73,
5344.
[29] K. Matsumoto, K. Usuda, H. Okabe, M. Hashimoto, Y. Shimada,
Tetrahedron: Asymmetry 2013, 24, 108.
[19] (R)-TRIP
= (R)-3,3′-Bis(2,4,6-triisopropylphenyl)-1,1′-binaphthyl-2,2′-
diyl hydrogenphosphate. See: S. Hoffmann, A. M. Seayad, B. List,
Angew. Chem. Int. Ed. 2005, 44, 7424; Angew. Chem. 2005, 117, 7590.
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10.1002/anie.201908299
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COMMUNICATION
Entry for the Table of Contents (Please choose one layout)
COMMUNICATION
T. Miura,* N. Oku, M. Murakami*
OH
1,1-diboration
1
2
O
(E)
Bpin
+
R1
R1
Page No. – Page No.
H
R2
R2
anti
transposition/
allylation/
Diastereo- and Enantioselective
d
Synthesis of (E)- -Boryl-Substituted
anti-Homoallylic Alcohols in Two
up to 98% ee
R1 =
Aryl, Alkyl
R2 =
H, Aryl, Alkyl
(MOM)O
isomerization
Steps from Terminal Alkynes
(E)-d-Boryl-substituted anti-homoallylic alcohols are synthesized in
a highly
diastereo- and enantioselective manner in two steps from terminal alkynes, i.e., (i) a
cobalt(II)-catalyzed 1,1-diboration reaction of terminal alkynes with B2pin2, and (ii)
an asymmetric allylation reaction of aldehydes with the resulting 1,1-di(boryl)alk-1-
enes in the presence of a palladium(I) catalyst and a chiral phosphoric acid.
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