Diborative Reduction of Alkynes to 1,2-Diboryl-1,2-Dimetalloalkanes: Its Application for the Synthesis of Diverse 1,2-Bis(boronate)s

Article abstract of DOI:10.1021/acs.orglett.9b01622

Reduction of alkynes with alkali metals in the presence of B₂pin₂ results in diboration of alkynes. Distinct from conventional dissolving metal hydrogenations, two carbon-boron bonds and also two carbon-alkali metal bonds can be constructed in one operation to form 1,2-diboryl-1,2-dimetalloalkanes. The 1,2-diboryl-1,2-dimetalloalkanes generated are readily convertible to a wide range of vicinal bis(boronate)s. In particular, oxidation of the 1,2-dianionic species provides (E)-1,2-diborylalkenes, unique anti-selective diboration of alkynes being thus executed.

Full text of DOI:10.1021/acs.orglett.9b01622

Letter
pubs.acs.org/OrgLett
Cite This: Org. Lett. XXXX, XXX, XXX−XXX
Diborative Reduction of Alkynes to 1,2-Diboryl-1,2-
Dimetalloalkanes: Its Application for the Synthesis of Diverse 1,2-
Bis(boronate)s
Fumiya Takahashi,† Keisuke Nogi,*,† Takahiro Sasamori,‡ and Hideki Yorimitsu*,†
†Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan
‡Graduate School of Natural Sciences, Nagoya City University, Yamanohata 1, Mizuho-cho, Mizuho-ku, Nagoya, Aichi 467-8501,
Japan
S
* Supporting Information
ABSTRACT: Reduction of alkynes with alkali metals in the
presence of B2pin2 results in diboration of alkynes. Distinct
from conventional dissolving metal hydrogenations, two
carbon−boron bonds and also two carbon−alkali metal
bonds can be constructed in one operation to form 1,2-
diboryl-1,2-dimetalloalkanes. The 1,2-diboryl-1,2-dimetalloal-
kanes generated are readily convertible to a wide range of
vicinal bis(boronate)s. In particular, oxidation of the 1,2-
dianionic species provides (E)-1,2-diborylalkenes, unique anti-
selective diboration of alkynes being thus executed.
eduction of C−C triple bonds by means of alkali metals is
hardly compatible with strongly reducing conditions and
normally undergo reductive decomposition. Therefore, reduc-
tive functionalizations of alkynes have been limited to useful
yet specific intramolecular reactions.4
R
one of the most fundamental transformations in organic
synthesis, as represented by dissolving metal reduction of
alkynes to give trans-alkenes (Scheme 1a).1,2 Naturally, such
We recently became interested in developing new trans-
formations based on the strong reducing ability of alkali
metals.5 During the course of our investigation, we accidentally
found that diborative reduction of alkynes 1 occurred in the
presence of bis(pinacolato)diboron (2, B2pin2) and alkali metal
to afford 1,2-diboryl-1,2-dimetalloalkanes 3-M2 (Scheme 1b).
Alkoxy-substituted B2pin2 is resistant to reduction by alkali
metals.6 On the other hand, because of the vacant p orbitals of
the boron atoms, B2pin2 can rapidly react with the vinylic
anionic species to suppress the undesired protonation or
oligomerization. Moreover, the vacant p orbitals of the boron
atoms installed render the 1,2-dianionic species 3-M2
sufficiently stable by delocalizing the negative charge. These
features allowed us to accomplish an unusual reductive
transformation of alkynes: the simultaneous formation of two
carbon−boron bonds and two carbon−alkali metal bonds in
one operation.
Scheme 1. Reductive Functionalization of Alkynes with
Alkali Metals
1,2-Dianionic species 3-M2 were converted to diverse 1,2-
diborylalkanes 4−7 via electrophilic trapping. Oxidation of 1,2-
dianionic 3-M2 with 2,3-dibromobutane furnished the
corresponding 1,2-diborylalkenes 8. Of note, the reaction
preferentially afforded E isomers that are otherwise difficult to
synthesize. This diborative reduction/oxidation sequence
represents a rare example of anti-selective diboration of
reduction always results in the formation of new C−H bonds
by in situ protonation. Introduction of other atoms or groups
besides hydrogens onto alkynes under strongly reducing
conditions has been far less investigated. To realize such
reductive functionalizations, the vinylic radical anion inter-
mediates should be rapidly trapped by aprotic electrophiles.
Otherwise, undesirable protonation or oligomerization3 of the
labile intermediates would occur. However, electrophiles are
Received: May 7, 2019
© XXXX American Chemical Society
A
DOI: 10.1021/acs.orglett.9b01622
Org. Lett. XXXX, XXX, XXX−XXX

Organic Letters
Letter
alkynes. Moreover, successive transformations of the two boryl
groups installed clearly demonstrate the synthetic utility of
bis(boronate)s 4−8.7,8
First, we tried to identify the structure of 3a-Li2 generated
from diphenylacetylene (1a), diboron 2 and Li metal.
Equimolar amounts of 1a and 2 were treated with 2 equiv of
Li granules in THF at room temperature (Scheme 2). The
Scheme 2. Synthesis of 3a-Li2 and a Possible Mechanism
desired 3a-Li2 gradually precipitated as yellow solids and was
obtained in 37% yield as a THF adduct. Recrystallization of 3a-
Li2 from THF afforded yellow crystals of 3a-Li2(thf)3, in which
one Li+ is coordinated by one THF molecule and the other Li+
is associated with two THF molecules.
Figure 1. Structures of two independent molecules (a) Y and (b) Z of
3a-Li2(thf)3. Thermal ellipsoids are drawn at 50% probability. All of
the hydrogen atoms and the cocrystallized molecules of THF have
been omitted for clarity. Selected bond distances (Å), angles (deg),
and torsion angles (deg) for Y: C1−C2 1.454(2), C2−C3 1.529(2),
C3−C4 1.454(2), C2−B1 1.482(2), C3−B2 1.478(2), C1−Li1
2.326(3), C2−Li1 2.187(3), C3−Li2 2.281(3), C4−Li2 2.659(3),
C1−C2−C3 119.0(1), C1−C2−B1 122.9(1), B1−C2−C3 117.8(1),
C2−C3−C4 119.1(1), C2−C3−B4 116.8(1), B2−C3−C4 122.2(1),
C1−C2−C3−C4 77.3(2), B1−C2−C3−B2 86.5(2). Structural data
for Z: C1′−C2′ 1.451(2), C2′−C3′ 1.526(2), C3′−C4′ 1.449(2),
C2′−B1′ 1.478(2), C3′−B2′ 1.482(2), C1′−Li1′ 2.342(4), C2′−Li1′
2.212(4), C3′−Li2′ 2.288(3), C4′−Li2′ 2.644(3), C1′−C2′−C3′
118.7(1), C1′−C2′−B1′ 123.0(1), B1′−C2′−C3′ 116.8(1), C2′−
C3′−C4′ 119.7(1), C2′−C3′−B4′ 114.0(1), B2′−C3′−C4′
123.7(1), C1′−C2′−C3′−C4′ 78.4(2), B1′−C2′−C3′−B2′ 82.5(2).
The structure of 3a-Li2(thf)3 was unambiguously deter-
mined by single-crystal X-ray diffraction analysis, as shown in
Figure 1.9,10 The unit cell of the crystal consists of two
independent molecules Y and Z having similar structural
parameters. The C2−C3 bonds (1.529(2) and 1.526(2) Å) are
significantly elongated compared with general CC triple
bonds and are regarded as single bonds. Conversely, the C2−
B1 (1.482(2) and 1.478(2) Å) and C3−B2 (1.478(2) and
1.482(2) Å) bonds are considerably shorter than C−B single
bonds (1.58−1.62 Å)11 and rather close to CB double
bonds (1.42−1.45 Å).11 The double-bond character of these
C−B bonds is also suggested by natural bond orbital (NBO)
analysis.12−14 Delocalization of the negative charge to the p
orbitals of the boron atoms would make the C−B bonds short.
Lithium cations Li1 and Li2 interact with C1 and C4,
respectively (C1−Li1, 2.326(3) and 2.342(4); C4−Li2,
2.659(3) and 2.644(3)), which indicates slight delocalization
of the negative charge to the benzene rings. The summations
of the angles around C2 (359.7° and 358.5°, C1−C2−C3,
C1−C2−B1, and B1−C2−C3) and C3 (358.1° and 357.4°,
C2−C3−C4, C2−C3−B4, and B2−C3−C4) are close to 360°,
which supports the sp2-hybridized character of C2 and C3.15 In
the crystalline state, the two planes defined by C1−C2−B1 and
C4−C3−B2 are found to be nearly orthogonal, as confirmed
by the torsion angles of 86.5(2)° and 82.5(2)° (B1−C2−C3−
B2).
To establish this reductive process to be useful in organic
synthesis, we then optimized the reaction conditions for the
formation of 1,2-diboryl-1,2-dimetalloalkane 3a-M2. A mixture
of alkyne 1a and B2pin2 was treated with 2 equiv of alkali metal
in THF at 0 °C for 0.5 h before the addition of iPrOH to form
1,2-diborylalkane 4a (Table 1; see Tables S1−S3 for more
details). When Li granules were used, the yield of 4a was only
12% (entry 1). Slow electron transfer attributed to the small
surface area of granular Li would be problematic. Although the
use of Li powder gave better results, the yield was not
satisfactory (entry 2). To accelerate the electron transfer, we
focused on Na dispersion having a large surface area (average
particle size < 10 μm) as an electron donor.18 To our delight,
the yield of 4a was dramatically improved to 88% (entry 3).
However, the diastereomeric ratio (d.r.) was lower than that
observed in the reaction with Li powder (entry 2). Considering
that Li cation would have a positive effect on the d.r., we
conducted the reaction with Na dispersion in the presence of 2
equiv of LiI. Although the selectivity was low when the
protonation was conducted at 0 °C, a 69% yield of 4a was
obtained with high d.r. (90:10) upon addition of iPrOH at
−78 °C (entries 4 and 5). In the absence of LiI, the d.r.
decreased to 60:40 even after protonation at −78 °C (entry 6).
A possible reaction mechanism for the generation of 3a-Li2
is depicted in Scheme 2. First, one-electron reduction of alkyne
1a would generate radical anion A, which would rapidly react
with 2 to form borate species B. Subsequently, the terminal
boryl group would migrate to the β-carbon to generate radical
anion C. Mechanistic investigations16 suggest that this boryl
migration would proceed intermolecularly: the terminal boryl
group would engage in nucleophilic attack onto the less
crowded radical-centered β-carbon of B. Finally, 3a-Li2 would
be generated via one-electron reduction of C.17
B
DOI: 10.1021/acs.orglett.9b01622
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Organic Letters
Letter
the para positions successfully underwent the reaction to afford
4b−d with moderate to high diastereoselectivity. Because of
the instability of 4d on silica gel, the isolated yield of 4d was
decreased to 28%. When dimethylaminocarbonyl-substituted
alkyne 1e was used, monoborylation product 9e was obtained
as a single product. After the formation of 1,2-diborylalkane 4e,
deborylative protonation would proceed to afford 9e because
of the resonance effect of the aminocarbonyl group. The
present diboration accommodates sterically hindered ortho-
substituted diarylacetylenes 1f and 1g to furnish 1,2-
diborylalkanes 4f and 4g, respectively. 2-Naphthyl-substituted
acetylene 1h took part in the reaction to furnish 4h with good
diastereoselectivity. The reaction of bis(2-thienyl)acetylene
(1i) afforded product 4i in 38% yield with 38% recovery of 1i.
Not only diarylacetylenes but also alkyl aryl acetylenes 1j and
1k could be involved in the reaction. tert-Butylacetylene 1j
afforded the threo isomer of 4j as the major product.
Interestingly, replacement of the tert-butyl group with a butyl
group reversed the stereoselectivity: the reaction of 1-phenyl-1-
hexyne (1k) mainly furnished erythro-4k with moderate
diastereoselectivity. Silyl substituents on the acetylenic carbons
of 1l and 1m endured the reaction; the corresponding
diboration products 4l and 4m were obtained in good yields.
The bulkier silyl group led to better erythro selectivity. Boron-
substituted alkyne 1n successfully underwent the reaction to
afford 1,1,2-triborylalkane 4n in 63% yield. Alkynes 1 should
have at least one aromatic ring on their acetylenic carbons; 5-
decyne (1o) was recovered after the reaction because electron
transfer from Na dispersion would not proceed.
Table 1. Optimization Study
entry
alkali metal
additive
NMR yield (%)
d.r.
1
2
3
4
Li granules
Li powder
none
none
none
LiI
LiI
none
12
37
88
69
69
75
82
65:35
82:18
64:36
63:37
90:10
60:40
90:10
Na dispersion
Na dispersion
Na dispersion
Na dispersion
Na dispersion
a
5
a
6
ab
,
7
LiI
a
b
iPrOH was added at −78 °C. 9/1 v/v THF/TMEDA.
Eventually, 4a was obtained in 82% yield with high d.r. by
using a THF/TMEDA (9/1 v/v) cosolvent system (entry 7).
With the optimal conditions in hand, we explored the
reaction scope with respect to alkynes 1 using proper aliphatic
alcohols (MeOH, iPrOH, or C6H13OH; see the Supporting
Information for details) for the protonation (Scheme 3).
Diarylacetylenes 1b−d possessing electron-donating groups at
Scheme 3. Scope with Respect to Alkynes
Surprisingly, changing the proton source from aliphatic
alcohols to more acidic phenols led to reversal of the
diastereoselectivity (Scheme 3, bottom). When the reactions
of diarylacetylenes 1a, 1b, and 1h were terminated with
phenols, the erythro isomers of 4a, 4b, and 4h were obtained as
the major products.
Twofold protonation of 1,2-dianion 3 would successively
proceed to afford 4, and the diastereoselectivity of 4 would be
determined in the second protonation step. After the first
protonation, the conjugate base of the proton source can
coordinate to the alkali metal or boron, which might affect the
diastereoselectivity of the second protonation. Indeed, the
stereoselectivity is roughly correlated to the acidity of the
proton source (see Table S3).
To demonstrate the versatility of 1,2-dianionic species 3, we
performed the reactions with several electrophiles for the
synthesis of a suite of bis(boronate)s (Scheme 4). Deuteration
of 3a-M2 with MeOD proceeded (Scheme 4a), and the major
isomer, threo-5, was isolated in 64% yield (93:7 d.r.; 96%
deuterium incorporation) by column chromatography on silica
gel. When dimethyl sulfate was used, 3a-M2 underwent
dimethylation to provide 6 (Scheme 4b). The threo isomer
(confirmed by X-ray crystallographic analysis; see Figure S3)9
was obtained as the dominant product and isolated as the
single isomer in 78% yield.19 Treatment of 3a-M2 with 1,3-
dichloropropane furnished the corresponding 1,2-diborylcy-
clopentane 7, but the yield was only 26%. It is known that 1,2-
disodiostilbene reacts with alkyl chlorides to provide alkylation
products in higher yields than 1,2-dilithiostilbene.19b−d Indeed,
the yield of 7 improved to 72% in the absence of LiI
(conditions in Table 1, entry 6). In contrast to the
dimethylation, the cycloalkylation preferentially afforded the
erythro isomer (Scheme 4c).20 The reaction with 1,3-
dichloropropane first generates a 3-chloropropylated anionic
a
b
alkyl−OH: MeOH, iPrOH, or C6H13OH. Determined by 1H NMR
c
d
analysis. Isolated as the 1,2-diol after oxidation with H2O2. aryl−
OH: 4-methoxyphenol or 2-tert-butyl-4-methoxyphenol.
C
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These results indicate that the stereoselectivity would be
determined by the steric repulsion between the original
substituents on the alkyne. Indeed, the use of trialkylsilyl-
substituted 1l and 1m stereoselectively afforded (E)-dibor-
ylalkenes 8l and 8m, respectively. Notably, the anti-selective
diboration was applicable to gram-scale synthesis: 1.2 g of 8a
(57% yield) was obtained from 5 mmol of 1a.
Scheme 4. Deuteration and Alkylations of 3a-M2
To validate the synthetic utility of the diborative reduction,
we undertook transformations of two of the bis(boronate)
products. According to the stereoretentive arylation of
alkylboronates with aryllithiums reported by Aggarwal,22
successive treatment of 5 with 1.1 equiv of 2-thienyllithium
and NBS provided the desired product 10 with one of the two
boron moieties being intact (Scheme 6a). Subsequent
Scheme 6. Derivatizations of Bis(boronate)s
intermediate, in which the two boronate moieties can interact
with each other through a sodium cation. The interaction
would fix the conformation of the intermediate to control the
final intramolecular alkylation, affording ethryro-7.
Next, we expected the synthesis of 1,2-diborylalkenes 8 via
oxidation of 1,2-diboryl-1,2-dimetalloalkanes 3-M2 by means of
a proper oxidizing reagent. After optimization of oxidants,
treatment of 3a-M2 with 2,3-dibromobutane was found to give
the corresponding 1,2-diborylstilbene 8a in 82% NMR yield.
To our surprise, the E isomer was obtained as the major
product and isolated in 57% yield by column chromatography
on silica gel (Scheme 5). In general, 1,2-diborations of alkynes
Scheme 5. anti-Diboration of Alkynes 1 via the Diborative
Reduction/Oxidation Sequence
oxidation of the C−B bond with H2O2 furnished deuterated
triarylethanol 11 in 75% yield over two steps. We also
attempted a formal synthesis of (Z)-tamoxifen, an antiestro-
genic anticancer drug, using (E)-1,2-diborylalkene 8a. By the
use of catalytic amounts of Pd2dba3 (dba = dibenzylideneace-
tone) and [HPtBu2Me][BF4],23 ethylation of 8a with bromo-
ethane was found to proceed satisfactorily, after a brief
optimization, at a reaction temperature as high as 60 °C and in
a short reaction time (0.5 h). The desired monoethylation
product 12 was obtained in 56% yield as a promising precursor
of (Z)-tamoxifen (Scheme 6b).24,25
In summary, we have developed a diborative reduction of
alkynes by means of B2pin2 and alkali metals. This diborative
reduction is distinct from conventional dissolving metal
hydrogenations in versatility and extensibility. A key
intermediate, 1,2-diboryl-1,2-dilithioethane 3a-Li2, was suc-
cessfully isolated and unambiguously characterized by single-
crystal X-ray diffraction analysis. 1,2-Dimetalloalkanes 3-M2
were prepared in a synthetically useful way and converted to a
wide range of valuable bis(boronate)s such as 1,2-dibor-
ylalkanes 4−7 and (E)-1,2-diborylalkenes 8 that are difficult to
obtain with existing methods.
proceed in a syn manner, and anti-selective diborations to
afford (E)-1,2-diborylalkenes are quite limited:21 the applicable
substrates are restricted to propargyl alcohols,21a alkynoates,21b
and alkynamides,8b or the use of a special diborane(4) reagent,
pinB−B(mesityl)2, is necessary.21c The present anti-selective
diboration based on the diborative reduction/oxidation
sequence is a unique and versatile method for the synthesis
of (E)-1,2-diborylalkenes.
Diarylacetylenes 1f and 1h also underwent the anti-
diboration to afford 8f and 8h in moderate yields (Scheme
5). tert-Butyl-substituted alkyne 1j was converted to (E)-8j
selectively, while the reaction of 1-phenyl-1-hexyne (1k)
furnished 8k with moderate stereoselectivity (E:Z = 75:25).
ASSOCIATED CONTENT
* Supporting Information
■
S
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.or-
glett.9b01622.
Experimental procedures, X-ray crystallographic analysis,
computational studies, and spectral data (PDF)
D
DOI: 10.1021/acs.orglett.9b01622
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Organic Letters
Cartesian coordinates of the optimized structure of 3a-
Letter
thesis of Ladder π-Conjugated Skeletons. Org. Lett. 2009, 11, 3076−
3079. (e) Araneda, J. F.; Neue, B.; Piers, W. E.; Parvez, M.
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Derivatives Through the Reduction of Alkynyl-Bridged Diboryl
Compounds. Inorg. Chem. 2018, 57, 12552−12561.
Li2(thf)3 (XYZ)
Accession Codes
CCDC 1908190, 1910932, 1911287, and 1911966−1911968
contain the supplementary crystallographic data for this paper.
These data can be obtained free of charge via www.ccdc.ca-
m.ac.uk/data_request/cif, or by e-mailing data_request@ccdc.
cam.ac.uk, or by contacting The Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CB2 1EZ, U.K.; fax:
+44 1223 336033.
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Lowering the Reduction Potential of a Boron Compound by Means of
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an Unsymmetrical Diborane(4). Chem. - Eur. J. 2015, 21, 4267−4271.
(7) For recent reviews of preparations and transformations of
bis(boronate)s, see: (a) Takaya, J.; Iwasawa, N. Catalytic, Direct
Synthesis of Bis(boronate) Compounds. ACS Catal. 2012, 2, 1993−
2006. (b) Xu, L.; Zhang, S.; Li, P. Boron-selective reactions as
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AUTHOR INFORMATION
Corresponding Authors
■
*knogi@kuchem.kyoto-u.ac.jp
*yori@kuchem.kyoto-u.ac.jp
ORCID
Keisuke Nogi: 0000-0001-8478-1227
Takahiro Sasamori: 0000-0001-5410-8488
Hideki Yorimitsu: 0000-0002-0153-1888
Notes
́
Ito, H.; Fernandez, E. Transition-Metal-Free B−B and B−Interele-
ment Reactions with Organic Molecules. Chem. Soc. Rev. 2017, 46,
415−430.
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(8) For selected recent examples of diborations affording 1,2-
bis(boronate)s, see: (a) Fang, L.; Yan, L.; Haeffner, F.; Morken, J. P.
Carbohydrate-Catalyzed Enantioselective Alkene Diboration: En-
hanced Reactivity of 1,2-Bonded Diboron Complexes. J. Am. Chem.
Soc. 2016, 138, 2508−2511. (b) Verma, A.; Snead, R. F.; Dai, Y.;
Slebodnick, C.; Yang, Y.; Yu, H.; Yao, F.; Santos, W. L. Substrate-
Assisted, Transition-Metal-Free Diboration of Alkynamides with
Mixed Diboron: Regio- and Stereoselective Access to trans-1,2-
Vinyldiboronates. Angew. Chem., Int. Ed. 2017, 56, 5111−5115.
(c) Peng, S.; Liu, G.; Huang, Z. Mixed Diboration of Alkynes
Catalyzed by LiOH: Regio- and Stereoselective Synthesis of cis-1,2-
Diborylalkenes. Org. Lett. 2018, 20, 7363−7366. (d) Yan, L.; Meng,
Y.; Haeffner, F.; Leon, R. M.; Crockett, M. P.; Morken, J. P.
Carbohydrate/DBU Cocatalyzed Alkene Diboration: Mechanistic
Insight Provides Enhanced Catalytic Efficiency and Substrate Scope. J.
Am. Chem. Soc. 2018, 140, 3663−3673.
This work was supported by JSPS KAKENHI Grants
JP16H04109, JP18H04254, JP18H04409, JP19H00895, and
JP18K14212. H.Y. thanks The Asahi Glass Foundation for
financial support. We thank KOBELCO ECO-Solutions Co.,
Ltd. for providing Na dispersion. We also acknowledge the
assistance of the Research Equipment Sharing Center at
Nagoya City University.
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=
1.169 g cm−3, μ = 0.077 mm−1, 2θmax = 52.0°, measd./unique reflns. =
64930/16352 (Rint = 0.0512), 989 parameters, GOF = 1.025, R1 =
0.0506/0.0649 [I > 2σ(I)/all data], wR2 = 0.1305/0.1418 [I > 2σ(I)/
all data], largest diff. peak and hole 0.647 and − 0.433 e Å−3.
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are shown in the Supporting Information.
(14) On the basis of NBO calculations, two NBOs were found
between B1−C2 and also between B2−C3. B1−C2: (1) σ bond
(1.953 e), B1(32%, sp1.29)−C2(68%, sp1.74); (2) π bond (1.724 e),
B1(22%, sp99.99)−C2(78%, sp99.99). B2−C3: (1) σ bond (1.951 e),
E
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Organic Letters
Letter
B2(32%, sp1.30)−C3(68%, sp1.75); (2) π bond (1.737 e), B2(21%,
sp99.99)−C3(79%, sp99.99).
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C2−C3, C2(50%, sp2.24)−C3(50%, sp2.28); C3−C4, C3(49%, sp2.02)−
C4(51%, sp1.84).
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presence of 0.50 mmol of B2pin2 (2) and bis(neopentylglycolato)
diboron (B2nep2), boron-scrambled product 4a″ was obtained (eq 1).
In addition, because 2 was recovered after treatment with Na
dispersion in the absence of 1a, reduction of 2 to boryl anion species
would be excluded. These results suggest that the boryl migration in
Scheme 2 would proceed intermolecularly.
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crucial because bromoethane was consumed by KOH at 60 °C.
(17) Other possible mechanisms are shown in Scheme S1.
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(20) The stereochemistry of threo-7 obtained as the minor product
was determined by X-ray crystallographic analysis (see Figure S4).9
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F
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