A modular olefination reaction between aldehydes and diborylsilylmethide lithium salts

Article abstract of DOI:10.1039/d1cc01882e

We describe the preparation of densely functionalised 1,1-silylborylated trisubstituted alkenes, via a boron-Wittig reaction, between LiC(Bpin)2(SiMe3) and aliphatic or aromatic aldehydes. The condensation of diborylsilylmethide lithium salts with α,β-unsaturated aldehydes provides a direct pathway to synthesize 1,1-silylborylated conjugated dienes and diynes.

Full text of DOI:10.1039/d1cc01882e

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A modular olefination reaction between aldehydes
and diborylsilylmethide lithium salts†
Cite this: Chem. Commun., 2021,
57, 6300
Oriol Salvado
and Elena Fernandez
*
´
Received 8th April 2021,
Accepted 24th May 2021
DOI: 10.1039/d1cc01882e
rsc.li/chemcomm
We describe the preparation of densely functionalised 1,1-silylborylated The introduction of silyl groups in the polyborylated reagent can be
trisubstituted alkenes, via a boron-Wittig reaction, between LiC(Bpin)2 used as an alternative strategy to control the stereoselectivity on the
(SiMe3) and aliphatic or aromatic aldehydes. The condensation of boron Wittig reactions, as well as a direct methodology to introduce
diborylsilylmethide lithium salts with a,b-unsaturated aldehydes pro- an extra functionality, however to the best of our knowledge only two
vides a direct pathway to synthesize 1,1-silylborylated conjugated approaches have been reported to date.5,6
dienes and diynes.
The reagent HC(Bpin)2(SiMe3) (1) was deprotonated in the
presence of LiTMP, to form a diborylsilyl stabilised carbanion at
The condensation reaction between carbonyl substrates and 0 1C. As a model substrate, benzaldehyde was added to the in situ
a-boryl carbanions, appointed as a boron-Wittig reaction, is prepared LiC(Bpin)2(SiMe3) in THF, at 0 1C. The reaction was
considered of great synthetic utility for the preparation of valuable warmed to room temperature and stirred for 16 h to accomplish
alkenes.1 The renaissance of the boron-Wittig reaction in 2010, the formation of the 1,1-silylborylated trisubstituted alkene 2,
has firmly consolidated the benefits of this type of condensation proving that B–O elimination is favoured versus Si–O Peterson
reaction using stable pinacolboryl (Bpin) moieties in the a-boryl elimination.7 The selectivity observed shows a preference for the
carbanions, but also controlling the stereoselectivity of the 2-E stereoisomer with the Bpin moiety syn with respect to the aryl
alkenes formed through the syn-B–O elimination (Scheme 1a)2 group, suggesting a favoured intermediate A versus A0 (Scheme 3a).
depending on the substrates3a or additives3b (Scheme 1b).
This is in contrast to the trend observed by Morken and co-workers,
The synthesis of trisubstituted vinyl boronates, via boron- on the boron-Wittig olefination between bis(pinacolboryl)methane
Wittig reaction between geminal bis(boronates) and linear or and aldehydes, in the presence of LiTMP, to furnish trans-
a-branched aldehydes, was addressed by Morken and co-workers, vinylboronate esters, through a plausible favoured B0 intermediate
with relative control over the selectivity (Scheme 2a).4 As a trend, (Scheme 3b).4 Despite the fact that the E:Z ratio for 2 is modest, it
they observed that the E isomer can be favoured when either bulky is noticeable to mention that the 2-E isomer has never been isolated
diborylated reagents or large aldehyde substituents (R0) are before. In fact, previous synthetic attempts, based on the hydro-
employed. In contrast, when small aldehydes (i.e., linear alkyl) boration of 1-phenyl-2-trimethylsilylacetylene, provided only the 2-Z
and small diborylated species are employed, the Z isomer seems to isomer as an expected B–H syn addition to the triple bond.8
be favoured. However, aromatic aldehydes were not studied in that
condensation reaction.
We next explored the condensation of picolinaldehyde with
1/LiTMP and the observed E:Z ratio on the trisubstituted alkene 3
Attending to the challenging boron-Wittig reaction when alde- increased slightly in THF or CPME as solvent (Scheme 4a), being the
hydes are involved, we became interested to launch a systematic first synthetic approach towards the 3-E since the 3-Z was prepared
study on the olefination with both aromatic and aliphatic aldehydes
in the presence of the reagent HC(Bpin)2(SiMe3) (1) with the aim to
get insights about the stereoselectivity on the formation of densely
functionalised 1,1-silylborylated trisubstituted alkenes (Scheme 2b).
´
´
`
Dept. Quımica Fısica i Inorganica, University Rovira i Virgili, Tarragona, Spain.
E-mail: mariaelena.fernandez@urv.cat
† Electronic supplementary information (ESI) available. CCDC 2060900. For ESI
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
d1cc01882e
Scheme 1 Boron-Wittig reaction of ketones for tri- and tetrasubstituted
alkenes.
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Scheme 5 Boron-Wittig reaction between benzaldehyde and LiCH(SiMe2
(2-Py)2).
(Scheme 5).11 That is an interesting point since the alternative
reaction between benzaldehyde and the reagent LiCH(SiMe3)2 pro-
duces the vinylsilanes only in E:Z ratio = 58 : 42.12,13
Scheme 2 Boron-Wittig reaction of aldehydes with (a) HC(Bpin)2(R) and
(b) HC(Bpin)2(SiMe3) for trisubstituted alkene synthesis.
Next, we observed that the boron-Wittig reaction of thiophene-
2-carbaldehyde and 1/LiTMP produces the corresponding trisub-
stituted alkene 4 in an improved E:Z ratio = 82 : 12 (Scheme 6).
Interestingly, 4-E is synthesised for the first time in this work
whereas 4-Z had been prepared through Lewis acid HB(C6F5)2-
catalysed hydroboration of trimethyl(thiophen-2-ylethynyl)silane
in 50% yield.14 Alternatively, we studied the condensation of
thiophene-2-carbaldehyde with LiC(Bhex)2(SiMe3) (Bhex = hexy-
lene glycolato boryl), generated in situ from HC(Bhex)2(SiMe3) (5)
and LiTMP. The product 6 was obtained with an E:Z ratio 83 : 17,
although the conversion was reduced to 70% probably due to the
steric hindrance associated to the Bhex moiety (Scheme 6). The
11B NMR signal at 28.9 ppm for 6-E might correlate with a subtle
S–B intramolecular interaction. Furan-2-carbaldehyde reacted
with 1/LiTMP providing a similar reaction outcome towards the
trisubstituted alkene 7 with a notably increased E :Z ratio of 91 : 1,
Scheme 3 Boron-Wittig reaction between benzaldehyde and (a)
LiC(Bpin)2(SiMe3) and (b) LiCH(Bpin)2 for comparison.
from catalytic hydroboration strategies.8c The stereocontrol with using both THF or CPME as a solvent (Scheme 6). The inter-
LiC(Bpin)2(SiMe3) contrasts with the one observed using mediate F has been suggested to justify the enhanced stereo-
LiCH(Bpin)2, since the trans-vinylboronate ester is generated exclu- selectivity observed in this reaction, through
a plausible
sively in 42% yield (Scheme 4b).3 Considering the plausible chair- intramolecular X–B interaction (X = O, S). Compound 7 has been
like intermediate, an intramolecular interaction between the N and prepared for the first time in this work.
the Bpin moiety, forming a five member ring in C, might explain the
Next, we performed several experiments to demonstrate that
observed enriched selectivity on 3-E.9 In fact, product 3-Z shows a steric and electronic modifications on aryl aldehyde substrates
characteristic 11B NMR signal at 32.5 ppm, whereas for 3-E the signal contributed not only to obtain the exclusive formation of
appears at 27.6 ppm as a consequence of the subtle N–B intra- stereoisomer E, but also to reverse the stereocontrol toward
molecular interaction. Scheme 4b shows that in the absence of formation of stereoisomer Z, depending on the substituents
chelation control, the intermediate D might predict the trans- present in the aryl group. Electron donating and electron
vinylboronate ester formation.10 For comparison, Yoshida and co- withdrawing groups in a para position do not change the
workers found that the reagent LiCH(SiMe2(2-Py)2) reacts with reaction outcome with a modest preference for the E-8 and
aldehydes to give the corresponding trans-vinylsilanes presumably E-9 stereoisomers (Scheme 7). Both are synthesised for the first
via stereodetermining intermediate E where the intramolecular time in this work, since only stereoisomers Z-8 and Z-9 are
chelation of the pyridyl group with Li+ locks the conformation known.8c,15 However, OMe substituents in an ortho position
seem to have a major influence on the E-stereocontrol for E-11
and E-12 in comparison to the influence of F towards E-10
Scheme 4 Boron-Wittig reaction between picolinealdehyde and (a)
Scheme 6 Boron-Wittig reaction between thiophene-2-carbaldehyde or
LiC(Bpin)2(SiMe3) and (b) LiCH(Bpin)2 for comparison.
furan-2-carbaldehyde with LiC(Bpin)2(SiMe3) or LiC(Bhex)2(SiMe3).
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Scheme 8 Boron-Wittig reaction between sterically hindered ortho sub-
stituted aryl aldehydes and HC(Bpin)2(SiMe3) (1)/LiTMP.
been prepared through catalysed hydrogenation of the corres-
ponding cyclic unsaturated substrates.18
The olefination of aliphatic aldehydes with 1/LiTMP has
demonstrated that steric factors might also influence the
stereoselective reaction outcome. Whereas the boron-Wittig of
2-phenylacetaldehyde generates the corresponding trisubsti-
tuted olefin 21 in 75 : 25 E : Z ratio, the olefination of substrate
2-phenylpropanal increases the ratio up to 86 : 14 E : Z in 22.
Interestingly, the most sterically hindered substrate, 2,
2-diphenylacetaldehyde, is transformed exclusively towards
the E-23 stereoisomer (Scheme 9). All these products could be
converted into valuable allylic 1,1-borylsilylalkanes by proton
abstraction/isomerization in the presence of LiTMP or LDA.
The allylic compounds 24–26 could be isolated in moderate
yield with exclusive E stereoselectivity and efficiently oxidised
towards a-(hydroxyallyl)silanes 27–29 (Scheme 9).
Finally, we explored the olefination of a,b-unsaturated
aldehydes with HC(Bpin)2(SiMe3)/LiTMP, resulting in a chemo-
selective preference on the nucleophilic attack of diborylsilyl-
methide lithium salt to the aldehyde functionality versus the
conjugated b position. Scheme 10 shows that cinnamaldehyde
condenses with LiC(Bpin)2(SiMe3) to give the trisubstituted
conjugated dienyl compound 30 in a 68 : 32 E : Z ratio, however
the analogue substrate 2-bromo-3-phenylacrylaldehyde con-
ducted the boron-Wittig reaction with LiC(Bpin)2(SiMe3)
towards the preferred formation of 31 in a 82 : 18 E : Z ratio.
Even higher stereoselectivity could be achieved using reagent
LiC(Bhex)2(SiMe3), generating product E-32 in a 92 : 8 E : Z ratio
(Scheme 10). Interestingly, the addition of 1.5 equiv. of KOtBu
Scheme 7 Substrate scope for stereoselective boron-Wittig reaction with
HC(Bpin)2(SiMe3) (1) and LiTMP.
(Scheme 7). However, higher stereoselectivity is achieved when
substrate 2,4,6-(OMe)3-C6H2 is transformed into product 13 in
97% yield as E : Z ratio 97 : 3 (Scheme 7). X-Ray diffraction of
E-13 shows a short B1–O5 length distance (2.76 Å) compared to
B1–O3 (4.81 Å), forcing a torsion angle C–CQC–C about 12.021.
It is suggested an attractive interaction between B1–O5 since the
covalent bond lengths are B1–O1 1.3796(8) and B1–O2 1.3794(8).
None of these polyfunctionalised products with ortho substitu-
ents have been prepared before. Interestingly, when the ortho
substituents are Cl, Br, I or CF3, we noticed that the Z stereo-
isomers became preferred in products 14–17.16 The reversed
trend might be correlated with steric effects of the silyl group
that controls the B–O elimination towards the preferred pro-
ducts 16 and 17 as E : Z 15 : 85 ratio (Scheme 7).
Similarly, sterically hindered ortho substituents are also
compatible with the boron-Wittig reaction, as it has been seen
in the synthesis of triaryl phosphine 18 in high yield and
preference on the Z stereoisomer (Scheme 8a). Surprisingly,
when 2-(methylsulfonyl)benzaldehyde reacted with reagent
1/LiTMP, the expected trisubstituted alkene 19 was scarcely
isolated (17% 19-E), and instead the cyclic system 20 was
detected and isolated (Scheme 8b). Its formation might be
postulated throughout the formation of (phenylsulfonyl)methy-
lene lithium intermediate (via deprotonation of the aryl sulfo-
nyl group with the excess of LiTMP)17 which interacts
intramolecularly with the alkene to form the cyclic saturated
Scheme 9 Selective trend in olefination of aliphatic aldehydes with
HC(Bpin)2(SiMe3)/LiTMP and subsequent proton abstraction/isomerization
compound 20. This type of benzothiophene 1,1-dioxide has and eventual oxidation.
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alkene formation. We have found that picolinaldehyde, thiophene-
2-carbaldehyde and furan-2-carbaldehyde could be involved in
stereodetermining intermediates via intramolecular interaction of
N, S or O with B. Also a divergent stereocontrol has been observed
when OMe ortho substituents in the aromatic aldehydes favour the
E-borylsilylalkane formation whereas halide ortho substituents sta-
bilise the Z-borylsilylalkanes. The condensation of a,b-unsaturated
substrates with LiC(Bpin)2[Si] allows access to 1,1-silylborylated
conjugated dienes and diynes, with relative high stereoselectivity.
´
We thank Ministerio de Economıa y Competitividad y por el
Fondo Europeo de Desarrollo Regional FEDER through project
PID2019-109674GB-I00. We thank AllyChem for the gift of
diboron reagents.
Conflicts of interest
There are no conflicts to declare.
Notes and references
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t
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t
¨
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t
t
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