1,3-Carboboration of iodonium ylides

Article abstract of DOI:10.1039/c9cc08749d

Herein, we disclose the utilisation of iodonium ylides to access a range of boron dienolates. Heating of acyclic iodonium ylides in the presence of different aryl boranes leads to the formation of rare 1,3-carboboration products. This methodology could not be expanded to cyclic iodonium ylides which instead formed a Lewis acid-base adduct. Products proved to be remarkably stable under a wide range of conditions allowing for their long term storage.

Full text of DOI:10.1039/c9cc08749d

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Mohajeri Thaker, D. Willcox, D. Ould, J. Wenz, J. M. Rawson, M. Hill, T. Wirth and R. Melen, Chem.
Commun., 2019, DOI: 10.1039/C9CC08749D.
Volume 54
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DOI: 10.1039/C9CC08749D
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1
,3-Carboboration of Iodonium Ylides
a
a
a,b
a
a
Theodore A. Gazis, Bayan A. J. Mohajeri Thaker, Darren Willcox, Darren M. C. Ould, Jan Wenz,
c
d
e
a
Jermey M. Rawson, Michael S. Hill, Thomas Wirth and Rebecca L. Melen *
Received 00th January 20xx,
Accepted 00th January 20xx
DOI: 10.1039/x0xx00000x
6 5 3 3
Herein, we disclose the utilisation of iodonium ylides to access a B(C F ) and RN followed by a Staudinger type reaction
1
0
range of boron dienolates. Heating of acyclic iodonium ylides in the (Scheme 1a). Conversely, metal-free 1,2-carboboration
presence of different aryl boranes lead to the formation of rare 1,3- reactions are much rarer, especially for sp-hybridised systems
1
1
carboboration products. This methodology could not be expanded which to date are limited to highly electrophilic borocations.
2
to cyclic iodonium ylides which instead formed a Lewis acid-base 1,2-carboboration of sp -centres has been exemplified through
12
adduct. Products proved to be remarkably stable under a wide the use of allenyl esters and ketones with B(C
6
5
F )
3
and recently
range of conditions allowing for their long term storage.
isocyanates leading to 4-membered cyclic compounds
exhibiting frustrated Lewis pair characteristics (Scheme 1b).13
The versatility of organoboranes in synthesis is beyond dispute.1
1
,2-carboboration of cyclic iminium ions with B(C
6 5 3
F ) , has also
2
From reaction intermediates (amination reactions ) to
been reported under photochemical conditions leading to
3
substrates (cross-coupling reactions ) and catalysts (e.g. Lewis
14
highly desirable tertiary amines. These transformations
demonstrate the proclivity of B(C to effect selectively 1,2-
4
5
acid catalysis or frustrated Lewis pair chemistry ) they
represent an invaluable tool in the arsenal of the synthetic
chemist. One such class of boranes, which has come to the
6 5 3
F )
aryl transfers. However, the corresponding 1,3-aryl transfers
are still an under-represented class of transformations. Aryl
transfer reactions utilising electrophilic boranes and diazo
species have been reported by Stephan, however these
forefront of modern Lewis acid chemistry, is that of the highly
6
electrophilic fluorophenyl boranes.
These boranes
demonstrate relatively high stability towards boron-carbon
hydrolytic cleavage. However the bond is sufficiently labile to
allow for its utilisation in a range of carboborations of sp- and
15
6 5
reactions were limited to the transfer of the C F moiety.
,
2
7
sp -hybridised bonds. Of these, 1,1-carboboration is the most
widely explored, partly thanks to the Wrackmeyer reaction, and
8
enables facile access to substituted olefins.
To date, alkynes remain the ‘go
carboborations with numerous examples reported. However,
recently, organic azides have been shown to undergo 1,1-
-
to’ substrate for 1,1-
9
6 5 3
carboborations with B(C F ) to generate imines. This reaction
was shown to proceed via an initial adduct formation between
a.
Cardiff Catalysis Institute, School of Chemistry, Cardiff University, Main Building,
Park Place, Cardiff, Cymru/Wales, CF10 3AT (UK).
E-mail: MelenR@cardiff.ac.uk
Department of Chemistry, University of Manchester, Oxford Rd, Manchester, M13
b.
9
PL, UK
c.
d.
e.
Department of Chemistry and Biochemistry, University of Windsor, 401 Sunset
Avenue, Windsor, Ontario N9B 3P4, Canada.
Department of Chemistry, University of Bath, Claverton Down, Bath, BA2 7AY
(
UK).
School of Chemistry, Cardiff University, Main Building, Park Place, Cardiff,
Cymru/Wales, CF10 3AT (UK).
Information about the data that underpins the results presented in this article,
including how to access them, can be found in the Cardiff University data catalogue
at http://doi.org/xxxx
Electronic Supplementary Information (ESI) available: Experimental procedures,
NMR spectra and details of the X-ray analyses of compounds. Crystallographic data
have been deposited with the CCDC (1935886, 1935888, 1935890, 1936166,
Scheme 1 Reported aryl transfer reactions from electrophilic boranes (
this work ( ).
a–c) and
d
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Recently, our group reported that transfer of other halogenated bond lengths, which are again in between single and double
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aryl groups to diazo species is possible (Scheme 1c).16 Given the bond character (1.389(3) Å and 1.396(3) Å). These metrics are
analogous nature between diazo species and iodonium ylides as comparable to related diketone structures reported by Chujo.20
DOI: 10.1039/C9CC08749D
17
carbene precursors, we envisaged that a similar aryl transfer The analogous reaction of hypervalent iodine starting material
should be viable. To this end, we divulge the reaction of 2a with equimolar quantities of boranes 1b proceeded in a
; Ar = 3,4,5- similar fashion furnishing the aryl transfer products in moderate
1d) and C to good yields (up to 67%) (Scheme 2). All products (3a-d
1e)) displaying varying levels of Lewis acidity (Scheme 1d).
Initial studies of the reaction of dimethyl 2-(phenyl-3
iodaneylidene)malonate [PhIC(CO Me)
–
d
F
F
iodonium ylides with a library of boranes (BAr
1a), 2,4,6-F 1b), 2,6-F 1c), C
(
3
3
F C
6
H
2
(
3
C
6
H
2
(
2
C
6
H
3
(
6
H
5
(
6
F
5
)
1
1
1
exhibited a broad resonance in the B{ H} NMR spectrum
between δ = 6.6 and 9.2. As with 3a, H NMR data confirmed
1
-
19
2
2
]
2a with borane 1a in the incorporation of the fluoraryl moiety and the F spectrum
refluxing dichloromethane led to a pale-yellow homogeneous resonances were consistent with two inequivalent fluoroaryl
solution. The colouration can be attributed to the generation of rings. Where yields are concerned, a tentative relationship to
18
iodobenzene. Subsequent workup and isolation afforded 3a Lewis acidity could be made. As shown in Scheme 2, an increase
1
1
1
as colourless crystals in 45% yield. The B{ H} NMR spectrum of in borane Lewis acidity (as determined by the Gutmann-Beckett
1
21
3
a
shows a broad resonance at δ = 7.5 ppm, while the H and method) provided a seemingly positive effect on the product
1
9
F NMR spectra were consistent with the incorporation of the yield. A notable exception is the reaction with B(C
6 5 3
F ) (1e)
3
,4,5-trifluorophenyl moiety showing two ring which led to an inseparable mixture of products (see ESI for
6 2 3
C H F
environments in a 2:1 ratio. The yield could be improved by crystal data of 3e), despite having a Lewis acidity comparable to
conducting the reaction in either chloroform or toluene (56% B(3,4,5-C . The characterization of by-products and
6 3 2 3
F H )
and 74% respectively) at 50 °C. Recrystallisation from a intermediates is always useful in evaluating mechanistic
dichloromethane/pentane solution led to single crystals whose pathways. In this context we re-examined the reaction of both
exact nature was elucidated by single crystal X-ray diffraction 1b and 1e with 2a on a larger scale as these produced the lowest
(
Figure 1). Compound 3a crystallised in the P-1 space group with isolated yields. Multinuclear NMR studies provided complex
four molecules present in the unit cell. The solid-state structure spectra from which no obvious hydrolysis product or reaction
shows the C B ring is non-planar and instead adopts an intermediate could be unambiguously identified. Attempted
2 2
O
envelope-type geometry, with the boron heteroatom sitting out recrystallizations using layering and solvent diffusion
of the plane and a fold angle (the angle between the OBO and techniques from a variety of solvent mixtures also proved
OCCO mean planes) of 23.3(3)°. The boron heteroatom is four unsuccessful.
coordinate and is slightly distorted from a tetrahedral
Having established the feasibility of transferring
geometry, with an O–B–O bond angle of 107.52(18)° (see ESI for fluorophenyl rings to symmetrical bis-ester stabilised ylides, we
further bond angles). The B–O bond lengths (1.523(3) Å and turned our attention to less stable iodonium ylides bearing an
1
.525(3) Å) were found to be slightly longer than typically ester and a ketone (2b), as well as a diketone (2c) (Scheme 3).
-
19
observed (1.468 Å in BO
4
)
and the C–O bond lengths were As before, reaction of 2b and 2c with tris(3,4,5-
found to be 1.287(3) and 1.288(3) Å, which is approximately trifluorophenyl)borane (1a) showed similar reactivity to that
intermediate between a single and double C–O bond with 2a resulting in the formation of 3f and 3g respectively. The
19
11
1
character.
B{ H} NMR spectrum showed a broad resonance at δ = 7.7
ppm for 3f and δ = 7.3 ppm for 3g consistent with a four-
coordinate boron centre with diminished Lewis acidity.
1
19
H and F NMR spectroscopic data were also consistent
with the formation of 3f and 3g. X-ray crystallography
unambiguously confirmed the structures of both products
1
(Figure 2). Compound 3f crystallised in the P2 /c space group
and has similar metrics to that of 3a, with a distorted
tetrahedral four-coordinate boron and B–O bond lengths
1
.488(3) Å and 1.540(3) Å. It was noted that the degree of
resonance appeared less in 3g than 3a, with C–O bond lengths
of 1.278(3) Å and 1.316(3) Å and C–C bond lengths of 1.366(4)
Å and 1.419(4) Å. Compound 3g, like 3a, crystallised in P-1 the
space group and again has similar metrics to 3a (see ESI for
further details). Repeated attempts were made to cleave the
boron moiety from compounds 3a-g to yield organic products in
which an aryl functionality had been incorporated. However,
these compounds proved remarkably stable and resistant to
Figure 1 Solid-state structure of 3a. C: black, B: pink, O: red, F: green. Thermal
ellipsoids drawn at 50% probability. H atoms omitted for clarity.
19
hydrolysis in both acidic and aqueous media, e.g. deprotection
using a variety of reagents all proved unsuccessful including: (i)
2 2 2 2 4 2
NaOH/H O ; (ii) Ag O/BnBr in MeCN; (iii) N H ·H O/AcOH in
This suggests resonance character is exhibited in the core
2 2
C O B six-membered ring, which is further observed in the C–C
2
| J. Name., 2012, 00, 1-3
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DOI: 10.1039/C9CC08749D
Scheme 2 Reaction of 2a with boranes 1a-d.
Figure 2 Solid-state structure of 3f and 3g. C: black, B: pink, O: red, F: green. Thermal
ellipsoids drawn at 50% probability. H atoms omitted for clarity.
Scheme 3 Reaction of iodonium ylides 2b and 2c with B(3,4,5-F
3 6
C H
)
2 3
1a.
.
EtOH (to form the equivalent pyrazole); (iv) Na
2
CO
3
in EtOH, H
2
O
then HCl. It was postulated that removing the ylide’s ability to
form stable intramolecular chelates would facilitate such a
cleavage. To test this, iodonium ylide 2d bearing a dimedone
motif was synthesised. Due to its conformational rigidity it was
envisaged that only a single oxygen atom would be available to
yield a B-O linkage thus facilitating hydrolysis. Yet, when 2d was
reacted with all boranes, unlike the acyclic iodonium ylides, a
complex mixture of products was formed in most cases. With
6 5 3
Scheme 4 Reaction of 2d with B(C F ) 1e.
In order to probe the reactivity of the Lewis acidic borane
with the iodonium ylide, a series of computational studies on
the formation of 3c were undertaken with the M06-2X
functional and LACVP+ basis set (see ESI for details). Initial
calculations probed adduct formation between the borane and
the iodonium ylide using the carbonyl O atom as a hard donor.
6 5 3
B(C F ) (1e) however adduct 4 was isolated and crystallised
(see ESI). This adduct proved to be resistant to elevated
temperatures (100 °C), precluding the carboboration reaction.
This indicates that a single B–O connection is not sufficient to
activate the boron and effect the transfer. However secondary
effects should not be discounted. It is reported that cyclic
iodonium ylides are more stable compared to their open chain
counterparts. This effect is imparted by secondary C-I----O
Adduct formation was computed to be strongly favourable (

E
-1
=
-115 kJ
·
mol ) and an analysis of the two conformers revealed
that the less sterically hindered conformation was more
-1
favoured by just 11 kJ
·
mol (Scheme 5). Reaction profiles for
2
3
bonding. However, this is a weak interaction that should be
readily disrupted at elevated temperatures. It is likely these two
factors work in a synergistic fashion preventing the aryl transfer.
migration of the aryl group to the ylidic carbon commencing
form both exo and endo adducts were explored and the
migration commencing from the more stable exo adduct passed
through a lower energy transition state. These studies reveal a
four-coordinate transition state with limited C-I bond
weakening (dC···I = 2.10 Å) reflecting an early transition state in
Adduct
4 shows short intermolecular O···I contacts in the solid-
state at 2.916 Å and 3.105 Å, slightly longer than those reported
2
3
6 5 3
for similar compounds in the absence of the B(C F ) adduct.
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Notes and references
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DOI: 10.1039/C9CC08749D
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6
H
3
F
)
2 3
and
6 3 2 2
C H F I=C(COOMe) .
9
1
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activation energy and led to the observed ring-closed product
as the most stable species on the potential energy surface.
1
1
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In summary, we have showcased an innovative route to boron
dienolates utilising iodonium ylides. This study revealed that
acyclic symmetrical iodonium ylides were successful substrates.
Unsymmetrical ylides were also amenable to this
transformation, whereas conformationally restricted cyclic
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reaction were unequivocally identified by X-ray crystallography.
Through the use of DFT computational studies, the net 1,3-
carboboration was shown to proceed via initial adduct formation
followed by an aryl migration coupled with elimination of aryl iodide
and finally, cyclisation. The generation of these aryl-substituted
products in a metal-free fashion provides a facile route to boron
containing heterocycles.
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Conflicts of interest
There are no conflicts to declare.
21 Q. Yin, Y. Soltani, R. L. Melen and M. Oestreich,
Organometallics, 2017, 36, 2381 – 2384.
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Acknowledgements
We are grateful to the EPSRC (T.A.G. P/L016443/1) and (R.L.M.
EP/R026912/1) for funding and the awarding of an EPSRC Early 24 G. S. Hammond, J. Am. Chem. Soc., 1955, 77, 334 – 338.
1
990, 46, 1300 – 1303.
Career Fellowship (R.L.M.). We also thank the Leverhulme Trust
(D.W. and R.L.M. RPG-2016-020) and NSERC (J.M.R. DG 2015-05523)
for financial support.
4
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