Generation and alkylation of 2-boryl allylic sulfone anions

Article abstract of DOI:10.1039/c3cc00030c

The deprotonation and electrophilic trapping of an allylic sulfone substituted at the 2 position by a pinacol boronate results in the formation of the corresponding alkylation products. The ability of the boronate ester to tolerate the sulfonyl carbanion suggests a broader application of the methodology to prepare a wide range of functionalized boronates. The Royal Society of Chemistry.

Full text of DOI:10.1039/c3cc00030c

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Generation and alkylation of 2-boryl allylic sulfone
anions†
Cite this: Chem. Commun., 2013,
49, 2365
Erich F. Altenhofer and Michael Harmata*
Received 2nd January 2013,
Accepted 5th February 2013
DOI: 10.1039/c3cc00030c
www.rsc.org/chemcomm
The deprotonation and electrophilic trapping of an allylic sulfone reported, very little chemistry associated with the substance has
substituted at the 2 position by a pinacol boronate results in the appeared.5 In addition to interests in coupling, we wondered what
formation of the corresponding alkylation products. The ability of the anion chemistry of such a species might be. We report herein
the boronate ester to tolerate the sulfonyl carbanion suggests a our preliminary results of studies in this context.
broader application of the methodology to prepare a wide range
of functionalized boronates.
We were intrigued by the possibility that 3 might be deproton-
ated and further functionalized to give more complex boronates. The
question was whether the boronate functional group would be
The ability to form carbon–carbon bonds between the organo- compatible with a sulfonyl-stabilized carbanion, since the boron
boron species and electrophilic partners has made Suzuki– atom is not conjugated to the atom(s) bearing the negative charge.
Miyaura (SM) cross-coupling reaction a powerful methodology The literature was not exceptionally helpful in providing answers.
used throughout organic synthesis.1 This has resulted in an However, some work by Whiting and co-workers in the early 1990s
explosion of syntheses utilizing the method, a wide availability suggested that the possibility of performing the desired transforma-
of boronic acids and their derivatives, and continuing interest tion was reasonable.6 This group reported that the boronate 4 could
in the development of new routes to organoboron compounds. be deprotonated and alkylated with methyl iodide and other simple
Polyfunctional organoboron compounds offer unique opportu- electrophiles like benzaldehyde (eqn (1)).
nities for making value-added structures containing boron. This is
especially important if the starting materials for such chemistry are
inexpensive and the subsequent chemistry relatively simple.
Recently, for example, Walsh has demonstrated the utility of a
bifunctional boronate in palladium-catalyzed allylation chemistry,
leading to more complex boronate-containing materials.2
(1)
We wanted to study the chemistry of compounds generically
represented by 1, ultimately to produce polyunsaturated systems
via coupling reactions for the development of various synthetic
methodologies involving pericyclic reactions. Our historic interest
We began our studies with 3. Although simple allylic sulfones are
easily deprotonated and alkylated,7 it was not clear at the outset what
we should expect with a nominally Lewis acidic atom in the molecule.
While attempted deprotonation of 3 with n-BuLi resulted in decom-
in sulfones led us to consider species like 2 and 3, both of which
are known compounds.3,4 Although the synthesis of 3 has been
position, the corresponding reaction with amide bases was more
promising. For example, treating 3 with excess LiHMDS followed
Department of Chemistry, University of Missouri-Columbia, Columbia,
Missouri 65211, USA. E-mail: harmatam@missouri.edu; Fax: +1-573-882-2754;
Tel: +1-573-882-1097
by trapping with excess iodomethane afforded the dialkylation
product 6 in 55% yield (eqn (2)). While we were pleased with this
result, we desired controlled monoalkylation at this stage of our work.
After considerable experimentation, we found that the best condi-
tions for such a reaction involved simple deprotonation with a slight
excess of LDA and electrophilic trapping to afford alkylation products
† Electronic supplementary information (ESI) available: Experimental proce-
dures, compound data and copies of 1H and 13C NMR; X-ray data for 7. CCDC
914468. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c3cc00030c
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Chem. Commun., 2013, 49, 2365--2367 2365

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in Table 1. Difficulties in handling allylic and benzylic iodides
led us to use the corresponding bromides as electrophiles
(Table 1, entries 6 and 7) and these were reasonably effective
in producing the targeted alkylation products. A single allylic
silane was also produced in moderate yield using TMSCl as the
electrophile (Table 1, entry 15).
Attempts to use primary chlorides or bromides in the alkylation
procedure were conducted using n-butyl electrophiles. While
n-butyl bromide afforded some monoalkylation product, large
amounts of starting material remained in the reaction mixture.
For n-butyl chloride, the reaction was messy and the only clean
compound that could be isolated was starting material.9 Secondary
iodides, isobutyryl iodide and neopentyl iodide gave only starting
material. Interestingly, solvents including dioxane, DME and
toluene afforded no alkylation product, though it seemed to be
the case from color changes that deprotonation of 7 was taking
place. Solubility problems were encountered with diethyl ether and
this solvent could not be used for the reaction.
The bases tested in the reaction included LiTMP, LiHMDS,
LTBTA10 and even n-BuLi. All of these bases were effective
to some degree in the alkylation process, but LDA was still
superior, followed closely by LiHMDS (see ESI†). Concentration
effects were interesting in that isolated yields were best at a
concentration of 0.1 M and worse at both higher and lower
concentrations. Thus, in the formation of 8c at 0.025 M, the
isolated yield was 27%; at 0.5 M, 42%. Even correcting for recovered
starting material did not increase the yield significantly.11
Scheme 1 Synthesis of 7.
Table 1 Deprotonation and alkylation of 7
Entry
‘‘R’’
Product
Yield (%)
1
2
Me
Et
8a
8b
8c
8d
8e
8f
8g
8h
8i
8j
8k
8l
8m
8n
8o
70
60
71
59
53
44
44
68
67
66
60
66
65
73
62
3
4
nPr
nBu
5
6
7
n-Heptyl
Allyla
Benzyla
8
9
3-Buten-1-yl
4-Penten-1-yl
5-Hexen-1-yl
4,6-Heptadien-1-yl
2-Phenyleth-1-yl
3-Phenylprop-1-yl
3-(2-Iodophenyl)prop-1-yl
10
11
12
13
14
15
b
SiMe3
Deprotonation was conducted at À78 1C. Alkylation reac-
tions proceeded at –78 1C, using n-propyl iodide as the electro-
phile, but were slow, affording a 1 : 0.7 ratio of 8c : 7 after three
hours. Good results were obtained from –30 1C to room
a
b
The corresponding bromide was used. The corresponding chloride
was used.
in good yield. Since we occasionally observed deprotonation and temperature with respect to alkylation, but it proved most
trapping at the methyl group of 3, as evidenced by spectroscopic simple to begin the alkylation at À78 1C then remove the
examination of crude reaction mixtures, we conducted the bulk of cooling bath and allow the reaction to proceed with gradual
our studies using its phenylsulfonyl analogue 7, whose synthesis warming to, and stirring at, room temperature.
paralleled that of 3 (ref. 4) and is shown in Scheme 1. The results for
the deprotonation and alkylation of 7 are summarized in Table 1.
In conclusion, we have developed a method for the straight-
forward alkylation of borylated allylic sulfones, thus opening the
door to the synthesis of a large number of new organoboron
species. Further studies of the chemistry of the products should
be fruitful in producing an even greater variety organoboron
compounds. For example, treatment of 8h with the second gen-
eration Grubbs catalyst afforded the intramolecular ring-closing
metathesis product 11 in 92% yield (Scheme 2).12 This compound
could be further alkylated by treatment with LDA and the triflate 12
to afford a 1 : 0.55 mixture (by 1H NMR) of regioisomers 13 and 14,
respectively, which could be transformed to a single product by
treatment with sodium phenyl sulfinate to afford 14 as the sole
regioisomer.13 A preliminary coupling experiment with 11 was
successful, but afforded 16 in relatively poor yield. Conversion of
11 to the corresponding potassium trifluoroborate14 improved the
process. Thus, coupling of 17 with 15 led to 16 in 70% yield.
This chemistry can blossom into many facile ways to
produce advanced organoboron species as well as other value-
added materials for synthesis.15 Exploration of the scope of
(2)
The synthesis of 7 involved the addition of phenylsulfonyl iodide
to the double bond in 9, presumably by a radical mechanism.
Elimination and presumably isomerization to the most thermo-
dynamically favored system afforded 7 in good yield. Compound 7 is
a crystalline solid. Interestingly, its solid state structure gave no
indication of an interaction between the formally Lewis acidic boron
atom and the oxygens of the sulfone group, though whether this
situation changes in its conjugate base is not yet known.8
The deprotonation and subsequent alkylation of 7 proceeded the alkylation reaction, the other processes shown, as yet
smoothly using LDA in THF and primary iodides as electro- unexplored processes and their mechanisms, is ongoing.
philes. Yields were fair to good in most cases, as shown Additional results will be reported in due course.
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2366 Chem. Commun., 2013, 49, 2365--2367
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Scheme 2 Exemplary chemistry of alkylation products of 7.
see: K. Durka, T. Klis, J. Serwatowski and K. Woznik, Appl. Organo-
met. Chem., 2011, 25, 669; For the generation of aryl magnesium
pinacol boronates via halogen–metal exchange, see: O. Baron and
P. Knochel, Angew. Chem., Int. Ed., 2005, 43, 3133.
7 B. M. Trost and C. A. Merlic, J. Org. Chem., 1990, 55, 1127;
B. M. Trost and N. R. Schmuff, J. Am. Chem. Soc., 1985, 107, 396;
A. Jonczyk and T. Radwan-Pytlewski, J. Org. Chem., 1983, 48, 910;
M. Ochiai, S. Tada, K. Sumi and E. Fujita, Tetrahedron Lett., 1982,
23, 2205; D. Savoia, C. Trombini and A. Umani-Ronchi, J. Chem. Soc.,
Perkin Trans. 1, 1977, 123.
8 The sum of the angles around the boron atom in 12 is 3601. See ESI†
for further details.
9 With n-butyl bromide the reaction afforded a 1 : 0.35 crude ratio of
12 : 14d, while the corresponding chloride afforded 12 and small
amounts of a complex mixture of products.
10 J. Busch-Petersen and E. J. Corey, Tetrahedron Lett., 2000, 41, 2515.
11 At 0.025 M the yield of 14c based on recovered starting material was
38%, at 0.5 M 45%.
12 B. Marciniec, M. Jankowska and C. Pietraszuk, Chem. Commun.,
2005, 663; C. Morrill, T. W. Funk and R. H. Grubbs, Tetrahedron
Lett., 2004, 45, 7733; C. Morrill and R. H. Grubbs, J. Org. Chem.,
2003, 68, 6031.
13 D. Knight and P. Lin, J. Chem. Soc., Perkin Trans. 1, 1987, 2707.
14 D. S. Matteson and G. Y. Kim, Org. Lett., 2002, 4, 2153; G. A. Molander
and B. Canturk, Angew. Chem., Int. Ed., 2009, 48, 9240.
This work has been sponsored by the US National Science
Foundation. We thank Frontier Scientific for a gift of 9. We
thank Materia for a gift of several metathesis catalysts. We
thank Dr Charles L. Barnes (Missouri-Columbia) for acquisition
of X-ray data.
Notes and references
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2 M. M. Hussain and P. J. Walsh, Angew. Chem., Int. Ed., 2010, 49, 1834.
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4 N. Guennouni, C. Rasset-Deloge, B. Carboni and M. Vaultier, Synlett,
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5 A. Belfaitah, M. Isly and B. Carboni, Tetrahedron Lett., 2004, 45, 1969.
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´
´
15 T. Klis, S. Lulinski and J. Serwatowski, Curr. Org. Chem., 2010,
14, 2549.
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This journal is The Royal Society of Chemistry 2013
Chem. Commun., 2013, 49, 2365--2367 2367