Tandem reactions involving 1-silyl-3-boryl-2-alkenes. New access to (Z)-1-fluoro-1-alkenes, allyl fluorides, and diversely α-substituted allylboronates

Article abstract of DOI:10.1021/ol4000263

The reactions of 1-silyl-3-boryl-2-alkenes with various electrophilic reagents (Selectfluor, N-halosuccinimides, benzhydryl, and propargylic alcohols in the presence of a Lewis acid, N-alkoxycarbonyliminium ion) have been investigated as new routes to α-substituted allylboronates. Further functional transformations, including allylboration, Suzuki coupling, protodeboronation, and cycloisomerization, have been carried out to illustrate the synthetic potential of these γ-borylallylsilanes.

Full text of DOI:10.1021/ol4000263

ORGANIC
LETTERS
2013
Vol. 15, No. 4
906–909
Tandem Reactions Involving 1‑Silyl-3-Boryl-
2-Alkenes. New Access to (Z)‑1-Fluoro-1-
Alkenes, Allyl Fluorides, and Diversely
r‑Substituted Allylboronates
†
†
‡
‡
ꢀ
ꢀ †
Aurelie Mace, Fabien Tripoteau, Qian Zhao, Eric Gayon, Emmanuel Vrancken,
Jean-Marc Campagne,‡ and Bertrand Carboni*,†
ꢀ
Institut des Sciences Chimiques de Rennes, UMR 6626 CNRS-Universite de Rennes 1,
Campus de Beaulieu, 35042 Rennes CEDEX, France, and Institut Charles Gerhardt
ꢀ
Montpellier, UMR 5253 CNRS-UM2-ENSCM-UM1, Ecole Nationale Superieure de
Chimie, 8, rue de l’Ecole Normale, F-34296 Montpellier, France
bertrand.carboni@univ-rennes1.fr
Received January 8, 2013
ABSTRACT
The reactions of 1-silyl-3-boryl-2-alkenes with various electrophilic reagents (Selectfluor, N-halosuccinimides, benzhydryl, and propargylic
alcohols in the presence of a Lewis acid, N-alkoxycarbonyliminium ion) have been investigated as new routes to r-substituted allylboronates.
Further functional transformations, including allylboration, Suzuki coupling, protodeboronation, and cycloisomerization, have been carried out to
illustrate the synthetic potential of these γ-borylallylsilanes.
Allylboronic esters and allylsilanes have been proven to
be highly versatile carbon nucleophiles, usually showing
very good levels of chemo-, regio-, and stereocontrol in
various reactions with electrophiles. Both of them can add
to carbonyl derivatives in the presence, or absence, of a
Lewis acid activator.1 In addition, allylboronic acids can
also be engaged in palladium-catalyzed cross-couplings2
and conjugate allylation of electron-deficient alkynes.3
Regarding allylsilanes, they are prone to halogen addi-
tion, dihydroxylation, epoxidation, cyclopropanation, and
Lewis acid mediated [2 þ 2]- and [3 þ 2]-annulation or free
radical additions.4
Reagents 1ꢀ5 possessing both trialkylsilyl and boronic
ester groups have enhanced synthetic potential when one
of them is in an allylic position (Figure 1).5ꢀ9
†
ꢀ
UMR 6626 CNRS-Universite de Rennes 1.
‡ UMR 5253 CNRS-UM2-ENSCM-UM1.
(3) Yamamoto, Y.; Yamada, S.; Nishiyama, H. Chem.;Eur. J. 2012,
18, 3153.
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3173.
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D. G. In Boronic Acids; Hall, D. G., Ed.; Wiley-VCH: Weinheim, 2005; pp
241ꢀ277. (b) Lachance, H.; Hall, D. G. Org. React. 2008, 73, 1. (c) Hall,
D. G Pure Appl. Chem. 2008, 80, 913. For reviews on allylsilanes, see:
(d) Masse, C. E.; Panek, J. S. Chem. Rev. 1995, 95, 1293. (e) Jacques, T.;
(5) For R-silylallylboronate 1, see: (a) Tsai, D. J.; Matteson, D. S.
Organometallics 1983, 2, 236. (b) Shimizu, M.; Kitagawa, H.; Kurahashi,
T.; Hiyama, T. Angew. Chem., Int. Ed. 2001, 40, 4283.
(6) For β-silylallylboronates 2, see: (a) Wu, J. Y.; Moreau, B.; Ritter, T.
J. Am. Chem. Soc. 2009, 131, 12915–12917. (b) Chang, K-J; Rayabarapu,
D. K.; Yang, F. Y.; Cheng, C.-H. J. Am. Chem. Soc. 2005, 127, 126.
(7) For β-borylallylsilanes 3, see: (a) Endo, K.; Sakamoto, A.;
Ohkubo, T.; Shibata, T. Chem. Lett. 2011, 40, 1440. (b) Ohmura, T.;
Oshima, K.; Suginome, M. Angew. Chem., Int. Ed. 2011, 50, 12501. (c)
Ohmura, T.; Suginome, M. Bull. Chem. Soc. Jpn. 2009, 82, 29.
ꢀ
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Marko, I. E.; Pospısil, J. In Multicomponent Reactions; Zhu, J., Bienayme,
´
H., Eds.; Wiley-VCH: Weinheim, 2005; pp 398ꢀ452.
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Soc. 2011, 133, 9716. (b) Gerbino, D. C.; Mandolesi, S. D.; Schmalz,
H-G; Podesta, J. C. Eur. J. Org. Chem. 2009, 3964. (c) Flegeau, E. F.;
Schneider, U.; Kobayashi, S. Chem.;Eur. J. 2009, 15, 12247. (d)
Yamamoto, Y.; Takada, S.; Miyaura, N.; Iyama, T.; Tachikawa, H.
Organometallics 2009, 28, 152. (e) Sebelius, S.; Olsson, V. J.; Wallner,
O. A.; Szabo, K. J. J. Am. Chem. Soc. 2006, 128, 8150.
r
10.1021/ol4000263
Published on Web 02/07/2013
2013 American Chemical Society

Scheme 1. Access to R-Substituted Allylboronates
Figure 1. Allylic reagents containing a trimethylsilyl and a
boronic ester group in an allylic position.
We started by studying the stereocontrolled synthesis
of (Z)-1-fluoro-1-alkenes 8 from 5 (Scheme 1, R = F,
Table1). Fluorinated molecules haveessentialapplications
in the life sciences, medicine, medical imaging, agrochem-
icals, and materials.18 A literature survey revealed several
methods for the synthesis of 1-fluoro-1-alkenes, including
Wittig type olefination, elimination reactions, addition
to alkynes, electrophilic addition, or metathesis.19 SN20
Displacement of an allylic fluoride atom of 3,3-difluoro-
propenes with organolithium reagents was also reported
recently.20 Herein, we disclose an alternative approach
based on a tandem electrophilic fluoration/allylation se-
quence from compounds 5 (Table 1).
The reactions of these bifunctional reagents with car-
bonyl compounds have been well documented, with some
specificity according to the location of the boron and
silicon atoms. For example, an interesting switch of selec-
tivity was observed when allylic compounds 1 were added
to aldehydes upon use of an acidic catalyst,10 while the
rhodium-catalyzed conjugate addition of 5 to enones
provided an efficient access to functionalized allylsilanes.9e
In natural product synthesis, allylboronic esters 4 have
found remarkable applications as building blocks for
amphidinoline E,11 hemibrevetoxin B,12mycalamine,13
dictyostatin,14 and bullatacin.15
The synthesis of starting allylsilanes featuring a boronic
ester group at the extremity of the double bond was
first carried out according to literature procedures: 5a by
Zr-catalyzed hydroboration of propargyltrimethylsilane
with pinacolborane (57%);21 5b by hydrogenation of
[3-(trimethylsilyl)-1-propyn-1-yl] boronic ester in the pre-
sence of the Lindlar catalyst in combination with quinoline
(77%);22 5c by bromoboration of 1-hexyne followed by
Pd-catalyzed cross-coupling with trimethylsilylmethylzinc
bromide (28%);23 and 5d by Pt-catalyzed diboration of
propargyltrimethylsilane (81%).24
Our interest in three-component reactions involving
organoboron reagents16 prompted us to explore the reactivity
of configurationally stable γ-borylallylsilanes 5 toward var-
ious electrophilic species. This could open efficient new routes
to R-substituted allylboronates 6, complementary to that
usually employed involving SN2 (or SN20) reactions on allyl
(or vinyl)boranes possessing a leaving group X R (or γ) to the
boron (Scheme 1).10,17 The resulting products could further
react with aldehydes or be involved in a cyclization process.
(8) For γ-silylallylboronates 4, see: (a) Zhang, P.; Roundtree, I. A.;
ꢀ
Electrophilic fluorodesilylation of 5 was carried out
using Selectfluor in acetonitrile in the presence of sodium
bicarbonate (Table 1).25 Due to the moderate stability of
the expected allyl fluoride 7,26 wedecided toperforma one-
pot fluorodesilylation/allyboration sequence from 5.
The corresponding homoallylic alcohols 8ꢀ16 were
obtained in moderate to good yields (35ꢀ71%, two
steps) with high stereocontrol. The structures of the major
Morken, J. P. Org. Lett. 2012, 14, 1416. (b) Selander, N.; Szabo, K. J.;
Aggarwal, V. K. Synthesis 2008, 2293. (c) Lira, R.; Roush, W. R. Org.
Lett. 2007, 9, 4315. (d) Jankowska, M.; Pietraszuk, C.; Marciniec, B.;
Zaidlewicz, M. Synlett 2006, 1695. (e) Dutheuil, G.; Hoffmann, R. W.;
Brinkmann, H.; Frenking, G. Chem. Ber. 1990, 123, 2387.
(9) For γ-borylallylsilanes 5, see: (a) Takaya, J.; Kirai, N.; Iwasawa,
N. J. Am. Chem. Soc. 2011, 133, 12980. (b) Selander, N.; Willy, B.;
Szabo, K. J. Angew Chem Int. Ed. 2010, 49, 4051. (c) Jankowska, M.;
Pietraszuk, C.; Marciniec, B.; Zaidlewicz, M. Synlett 2006, 1695. (d)
Morill, C.; Funk, T. W.; Grubbs, R. H. Tetrahedron Lett. 2004, 45, 7733.
(e) Yamamoto, Y.; Fujita, M.; Miyaura, N. Synlett 2002, 767. (f) Pereira,
S.; Srebnik, M. Organometallics 1995, 14, 3127.
(10) Carosi, L.; Lachance, H.; Hall, D. G. Tetrahedron Lett. 2005, 46,
8981.
(11) Va, P.; Roush, W. R. J. Am. Chem. Soc. 2006, 128, 15960.
(12) Zakarian, A.; Batch, A.; Holton, R. A. J. Am. Chem. Soc. 2003,
125, 7822.
(13) Marron, T.; Roush, W. R. Tetrahedron Lett. 1995, 36, 1581.
(14) Shimp, H. L.; Micalizio, G. C. Tetrahedron 2009, 65, 5908.
(15) Tinsley, J. M.; Mertz, E.; Chong, P. Y.; Rarig, R. A; Roush,
W. R. Org. Lett. 2005, 7, 4245.
(18) (a) Fluorine in Medicinal. Chemistry and Chemical Biology;
Ojima, I., Ed.; Wiley-Blackwell: United Kingdom, 2009. (b) Purser, S.;
Moore, P. R.; Swallow, S.; Gouverneur, V. Chem. Soc. Rev. 2008, 37, 320.
(c) O’Hagan, D. Chem. Soc. Rev. 2008, 37, 309. (d) Modern Fluoro-
organic Chemistry: Synthesis, Reactivity, Applications; Kirsch, P., Ed.;
Wiley-VCH; Weinheim, 2005.
(19) For a recent pertinent review, see: Landelle, G.; Bergeron, M.;
Turcotte-Savard, M. O.; Paquin, J.-F. Chem. Soc. Rev. 2011, 40, 2867.
(20) Bergeron, M.; Johnson, T.; Paquin, J.-F. Angew. Chem., Int. Ed.
2011, 50, 11112.
(21) Pereira, S.; Srebnik, M. Organometallics 1995, 14, 31278.
(22) Srebnik, M.; Bhat, N. G.; Brown, H. C. Tetrahedron Lett. 1988,
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4092.
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Carboni, B. Chem.;Eur. J. 2011, 17, 13670. (b) Berree, F.; Gernigon,
N.; Hercouet, A.; Lin, C. H.; Carboni, B. Eur. J. Org. Chem. 2009, 329.
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(c) Hercouet, A.; Berree, F.; Lin, C. H.; Toupet, L.; Carboni, B. Org.
Lett. 2007, 9, 1717. (d) Gao, X.; Hall, D. G.; Deligny, M.; Favre, A.;
Carreaux, F.; Carboni, B. Chem.;Eur. J. 2006, 12, 3132.
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M.; Trombini, C. Eur. J. Org. Chem. 2002, 2823. (c) Schlapbach, A.;
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(26) Although 7a was identified in the crude 1H NMR spectrum, we
were unable to isolate it with satisfactory yield and purity.
Org. Lett., Vol. 15, No. 4, 2013
907

fluorination in the presence of hydroquinidine-2,5-diphenyl-
4,6-pyrimidinediyldiether as a chiral additive.28
Table 1. Electrophilic One-Pot Fluorodesilylation/Allylboration
The presence of two boronic ester groups significantly
increases the synthetic potential of 1-silyl-3-boryl-2-
alkenes. In the case of 5d, the fluorodesilylation/allyboration
sequence can be followed by a Suzuki coupling or a borono-
Mannich condensation to afford the alcohol 18 or the
aminoester 19. The coupling can also be directly carried out
regio- and stereoselectively at the terminal over the internal
B-pin.29 A second coupling with another aryl bromide then
provided the allylsilane 23, a precursor of the allylic fluoride
24. The same groups were directly introduced if 2 equiv of
aryl bromide were engaged in the first step (Scheme 2).
Scheme 2. Access to Vinylic and Allylic Fluorides from 5e
In a similar way, other halosuccinimides can be used to
achieve electrophilic halogenations of 5a. The reaction
with N-iodosuccinimide was completed within 30 min to
give 25 which slowly isomerized to the rearranged allylic
iodide 26 (X = I) (20% after 1 h at rt) (Scheme 3). In the
presence of an aldehyde, the homoallylic alcohol 27 was
obtained in a low yield due to this competitive isomeriza-
tion phenomenon. With N-bromosuccinimide, due to a
slower 1,3-bromine migration, 1-bromoalkene 28 was
produced in a better yield (43%, two steps, Z/E: 92/8).
With the chloro derivative, the reaction proceeded to
completion for 5 d at 60 °C without any trace of the
corresponding allylic chloride 26 (X = Cl).30
a Isolated yields after column chromatography. b Measured by 19F
NMR on the crude product. c Mixture of anti/syn isomers (55:45). d The
Z/E ratio was determined by 1H NMR on the crude product.
(Z)-isomers were determined by 1H NMR analysis:
1
1
JHCdCH = 4.5ꢀ4.7 Hz for 8ꢀ15, Hꢀ H NOESY and
1
19Fꢀ H HOESY experiments for 16. The stereochemical
course of the allylation step resulted from a preferred
transition state where the F-atom adopts a pseudoaxial
position, as mentioned in the literature for polar
R-substituents.27 Best results in terms of yield and isomeric
purity were obtained with electron-deficient aldehydes,
such as 4-nitrobenzaldehyde or ethyl glyoxylate (entries 4
and 6). All attempts to extend these results to the enantioen-
riched homoallylic alcohols failed, either from an (S,S)-1,2-
dicyclohexylethanediol boronate 5a0 or by carrying out the
Regarding carbon electrophiles, these can also be used
in similar desilylation processes. With benzhydryl alcohol
or propargylic alcohols, in the presence of 10 mol % of
iron trichloride in methylene chloride, 5a afforded the
(28) Ma, J. A.; Cahard, D. Chem. Rev. 2004, 104, 6119.
(29) Ishiyama, T.; Yamamoto, M.; Miyaura, N. Chem. Lett. 1996, 25,
1117.
(30) The chloro derivative 24 was stable on storage, whereas the corre-
sponding bromide deteriorated rapidly. Hoffmann, R. W.; Landmann, B.
Tetrahedron Lett. 1983, 24, 3209.
(27) (a) Hoffmann, R. W. Pure Appl. Chem. 1988, 60, 123. (b)
Hoffmann, R. W.; Wolff, J. J. Chem. Ber. 1991, 124, 563.
908
Org. Lett., Vol. 15, No. 4, 2013

Scheme 3. Electrophilic Halogenations of 5a
Scheme 5. Transformations of Allylboronates 30ꢀ32
corresponding allylboronates 30ꢀ32 in 62ꢀ85% yields
(Scheme 4).31,32
mixture of diastereoisomeric N-protected allylamine 37 in
a modest unoptimized 35% yield, a N-protected boron
analogue of β-amino carboxylic ester38 (Scheme 6). Addi-
tion to benzaldehyde afforded the N-protected amino
alcohol 38 as a mixture of four stereomers.
Scheme 4. FeCl3-Catalyzed Allylation of Benzyhydrol and
Propargylic Alcohols with 5a
Scheme 6. Lewis Acid Catalyzed Allylation of Iminium Species
with 5a
These compounds can be used in further functional trans-
formations. The addition of benzaldehyde to 30 afforded
the homoallylic alcohol 33 as a 25/75 mixture of E/Zisomers
in 60% yield, while 34 was obtained with high Z-selectivity
(93/7) following the protodeboronation procedure recently
reported by V. K. Aggarwal (Scheme 5).33 Since 1,5-enynes
constitute an interesting class of substrate, where cyclo-
isomerization under transition metal catalysis leads to highly
functionalized carbocyclic structures,34 we also investigated
the behavior of 31ꢀ32 in the presence of metal catalysts.35
Complex mixtures were produced with (Ph3P)AuCl,
In summary, we have shown that 1-silyl-3-boryl-2-
alkenes5 are valuable precursors of diverselyR-substituted
allylboronates. Electrophilic fluorodesilylation can be ap-
plied as an efficient entry to (Z)-1-fluoro-1-alkenes and
allyl fluorides, while their addition to activated alcohols in
the presence of a Lewis acid afforded bicyclic compounds
after platinum dichloride cyloisomerization. Studies are un-
derway to expand this chemistry to enantioselective allylation
reactions of other differently substituted γ-borylallylsilanes.
Au(OAc)3, NaAuCl4 2H2O, and Na2PdCl4. By contrast,
3
upon moving to PtCl2, the boronated bicyclic products
35ꢀ36 were isolated in moderate yields (Scheme 5).
Other carbon electrophiles can also be involved in
similar desilylation processes. Thus, acyliminium, formed
in situ by mixing butyraldehyde and benzylcarbamate in
the presence of boron trifluoride etherate,36,37 led to a
Acknowledgment. The authors are grateful to D.
Cahard, IRCOF, Rouen, France for the gift of hydroquini-
dine-2,5-diphenyl-4,6-pyrimidinediyldiether and to J.P.
ꢀ
Guegan, Universite de Rennes 1, France, for NOESY and
HOESY experiments.
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^
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Supporting Information Available. Experimental de-
tails and characterization data for all new compounds.
This material is available free of charge via the Internet at
http://pubs.acs.org.
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The authors declare no competing financial interest.
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