Zinc-catalyzed functionalization of Si-H bonds with 2-furyl carbenoids through three-component coupling

Article abstract of DOI:10.1002/chem.201501155

A three-component coupling of alk-2-ynals, 1,3-dicarbonyls and silanes is reported. ZnCl₂ serves as an inexpensive and low-toxic catalyst for the overall transformation, which involves Knoevenagel condensation, cyclization, and carbene Si-H bon

Full text of DOI:10.1002/chem.201501155

DOI: 10.1002/chem.201501155
Communication
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Multicomponent Reactions |Hot Paper|
Zinc-Catalyzed Functionalization of SiÀH Bonds with 2-Furyl
Carbenoids through Three-Component Coupling
Sergio Mata, Luis A. López,* and RubØn Vicente*[a]
Dedicated to Professor JosØ Barluenga on the occasion of his 75th birthday
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Abstract: A three-component coupling of alk-2-ynals,
1,3-dicarbonyls and silanes is reported. ZnCl2 serves as an
inexpensive and low-toxic catalyst for the overall trans-
formation, which involves Knoevenagel condensation,
cyclization, and carbene SiÀH bond insertion. The process
takes place with high atom economy in the absence of
organic solvents and shows a broad scope. This reaction is
also applicable to the functionalization of oligomeric
siloxanes.
Silanes are an important class of compounds in chemistry.[1]
With respect to organic chemistry, synthetic applications of or-
ganosilanes have been established as routine protocols. Thus,
named reactions based on the use of compounds bearing silyl
groups such as Hiyama coupling, Sakurai allylation, Peterson
olefination, or Brook rearrangements, among others, are
commonly used synthetic tools.[1c,2] Moreover, the natural
abundancy of silicon, the stability of organosilanes and silox-
anes, their low toxicities, and macroscopic properties have
made silicon-based materials and polymers essential for our
society.[3] Considering the significance of silanes, the develop-
ment of efficient methodologies for their synthesis is a topic of
continuous interest. Several methods have been employed to
prepare organosilanes, including reactions of organometallics
with halosilanes[4] or metal-catalyzed cross-couplings[5] and hy-
drosilylations using hydrosilanes.[6] Moreover, transition-metal-
catalyzed insertion of carbenes or carbenoids, generated from
stabilized diazocompounds, into SiÀH bonds is one of the
most efficient tools for the functionalization of silanes.[7,8] As
an alternative to the use of diazocompounds, diiodoalkanes
(A) and Et2Zn can be employed to generate Simmons-Smith-
type carbenoids capable of inserting into the SiÀH bond of
simple silanes (B) (Scheme 1, top).[9] Unfortunately, stoichiomet-
ric amounts of moisture/air sensitive Et2Zn are required to ac-
complish this reaction. We have recently disclosed a methodol-
ogy to generate zinc carbenoids in a catalytic fashion using
enynones (D) as a source of furyl zinc carbene intermediates
(F), which could be efficiently trapped in situ with silanes
through a SiÀH bond insertion (Scheme 1, middle).[10] This
transformation could be accomplished with catalytic amounts
of inexpensive and low toxic ZnCl2.
Scheme 1. Zinc-promoted functionalization of SiÀH bonds: stoichiometric
vs. catalytic multicomponent approaches.
if an operationally simpler and environmentally more benign
three-component protocol could be developed (Scheme 1,
bottom). According to this hypothesis, ZnCl2 might operate as
a single catalyst to promote a three step sequence: 1) Knoeve-
nagel condensation, 2) 5-exo-dig cyclization, and 3) SiÀH bond
insertion. The overall process could be considered as zinc self-
relay catalysis.[13] Herein, we disclose the findings that have
allowed us to accomplish a multicomponent reaction with an
overall similar efficiency with respect to the standard stepwise
approach showing an expanded scope, which includes the
functionalization of diversely substituted silanes and oligo-
siloxanes.
As benchmark substrates, commercially available reagents
2,4-pentanedione (1a), oct-2-ynal (2a), and triethylsilane (3a)
were selected to explore the feasibility of a zinc-catalyzed mul-
ticomponent coupling to yield furan derivative 4a. Tempera-
ture, relative ratio of reagents, and catalyst loading were
screened.[14] Optimal reaction conditions involved the use of
a slight excess of the silane 3a (6 equiv), 5.0 mol% of ZnCl2,
and mild heating at 608C to afford 4a in 73% yield
(Scheme 2).[15] It is noteworthy that the use of an organic
solvent was not required and H2O was the only generated
by-product, which did not compromise the efficiency of the
reaction. This multicomponent protocol yielded 4a with com-
Multicomponent domino reactions have been shown to be
archetypal examples of efficient and sustainable processes.[11]
Because enynones (D) are prepared by Knoevenagel condensa-
tion (between compounds G and H), and Lewis acids such as
ZnCl2 can catalyze this type of condensation,[12] we wondered
[a] S. Mata, Dr. L. A. López, Dr. R. Vicente
Departmento de Química Orgµnica e Inorgµnica e Instituto Universitario de
Química Organometµlica “Enrique Moles”
Universidad de Oviedo
C/Juliµn Clavería 8, 33006-Oviedo (Spain)
E-mail: lalg@uniovi.es
vicenteruben@uniovi.es
Scheme 2. Zinc-catalyzed three component coupling. Optimized conditions:
1a (1.1 equiv), 2a (0.2 mmol), 3a (6.0 equiv), ZnCl2 (5.0 mol%), 608C, 16 h
(yields refer to isolated products).
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/chem.201501155.
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parable efficiency to that observed when using previously syn-
thesized enynone (73% and 77%, respectively).[10] Moreover,
the process could be scaled-up to 50-fold (10 mmol scale)
providing 4a in an even higher yield (88%, 2.83 g).
The optimized reaction conditions were then applied to
study the scope of this multicomponent coupling (Scheme 3).
1,3-Dione 1a and triethylsilane (3a) were combined with a
ketoesters as the 1,3-dione component, the reaction took
place chemoselectively through the ketone moiety to afford
4l–m and 4o in spite of the poor selectivity of the Knoevena-
gel condensation.[17] Next, we evaluated the scope with respect
to the silane coupling partner. Trisubstituted silanes bearing
alkyl or aryl groups could be employed, yielding compounds
4n–q with similar efficiencies. Though triethoxysilane proved
unreactive under various reaction conditions tested, inexpen-
sive siloxysilanes, readily available in bulk quantities, could also
be functionalized with the present procedure to lead to com-
pounds 4r–s in synthetically useful yields. Other valuable moi-
eties were tolerated in the silane. For instance, alkynylsilane
participated in the reaction, leading to densely functionalized
compounds 4t–u. 2-Silyl-substituted indole was also a compe-
tent coupling partner, affording silane 4v, albeit in lower yield
(45%, the two-component procedure led to 4v in 80% yield).
Finally, di- and mono-substituted silanes were studied as well.
The corresponding silanes 4w–z were obtained, albeit in lower
yields when compared with the two-component procedure.[18]
The present multicomponent procedure leads to furan deriv-
atives 4 in almost comparable yields to those obtained from
two-component approach (except for 4v, 4x, and 4y). Aside
from its remarkable efficiency, advantages with respect to the
operational simplicity, minimization of waste, and the scale-up
feasibility are noteworthy features of this three-component
coupling to consider it as the procedure of choice.
Geminal bis(silanes) represent a special type of organosilane
with potential synthetic applications as coupling reagents due
to their bifunctional character given by this particular struc-
ture.[19,20] In view of that, we next explored the feasibility to
apply this multicomponent coupling to access orthogonally
substituted geminal bis(silanes) by means of commercially
available 3-(trimethylsilyl)propiolaldehyde (2k). Thus, when al-
kynal 2k was subjected to optimized reaction conditions using
1,3-dione 1a and triethylsilane (3a), geminal bis(silane) 5a was
obtained in 61% yield (Scheme 4). Subsequent modifications
of the 1,3-dione led to compounds 5b–c in similar yields. With
respect to the silane coupling partner, a dialkylarylsilane, siloxy-
Scheme 3. Scope of reaction. Reaction conditions: 1 (0.3 mmol), 2
(1.1 equiv), 3 (6.0 equiv), ZnCl2 (5.0 mol%), 608C, 12–16 h. Yields refer to
isolated products. The values in parenthesis indicate the yield for the two-
component reaction using the corresponding enynone and ZnCl2 (10 mol%)
at ambient temperature. [a] See ref. [16]. [b] CH2Cl2 (0.5 mL) was used as
solvent.
variety of alkyl-substituted alkynals, including primary, secon-
dary,[16] tertiary, or remotely functionalized alkyl groups to yield
compounds 4a–f in moderate to good yields. The use of 1-
cyclohexenyl-substituted alkynal led to allylsilane 4g in 61%
yield. Aryl-substituted alkynals with different electronic proper-
ties also proved to be suitable substrates, providing com-
pounds 4h–j. Modifications of the 1,3-dione were feasible, as
shown in compounds 4k–m and 4o–p. Notably, when using
Scheme 4. Zinc-catalyzed synthesis of orthogonally substituted geminal
bis(silane) derivatives 5.
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silanes, or an alkynylsilane could be employed for the SiÀH
bond insertion to afford geminal bis(silanes) 5d–g.
without using organic solvents or harmful residue generation
since H2O is the only by-product. The broad scope regarding
all coupling partners is remarkable. Thus, the procedure was
used for the synthesis of interesting unsymmetrically substitut-
ed geminal bis(silanes). Moreover, the functionalization of SiÀH
bonds in representative oligosiloxanes exemplifies the feasibili-
ty to apply this reaction in a relevant field such as polymeric
advanced material modifications.
Polysiloxanes and silicones have been considered com-
pounds with marked economic significance for decades.[21] Be-
cause of their versatility and unique chemical, physical, and
electrical properties, polysiloxanes and silicones play a relevant
role among advanced materials with widespread applications
in products ranging from biomedicine to consumer electron-
ics.[3,22] As a result of the unquestionable importance of these
compounds, methodologies that enable the modification of
polysiloxanes to modulate their properties are always in
demand. To demonstrate the utility of the methodology
developed in this work as a tool with potential applications in
materials science, we evaluated the functionalization of SiÀH
bonds in representative low-molecular weight oligosiloxanes
(Scheme 5). Initially, simple 1,1,3,3-tetramethyldisiloxane (3i)
Acknowledgements
Financial support from MINECO of Spain (grant no. CTQ2013-
41511-P) and Principado de Asturias (“Severo-Ochoa” Program,
fellowship to S. M.) is gratefully acknowledged. R.V. is a Ramón
y Cajal fellow. We thank Prof. Dr. J. M. Gonzµlez for helpful
discussions and Dr. I. Merino (Universidad de Oviedo) for
her assistance in the NMR studies.
Keywords: multicomponent reactions · oligosiloxanes · SiÀH
bond functionalization · silanes · zinc catalysis
[1] a) I Ojima, Z. Li, J. Zhu in The Chemistry of Organic Silicon Compounds
(Eds.: Z. Rappoport, Y. Apeloig), Wiley, Chichester, 1998; b) M. A. Brook,
Silicon in Organic, Organometallic, and Polymer Chemistry, Wiley-VCH,
Weinheim, 2000; c) N. Auner, J. Weis, Organosilicon Chemistry, Wiley-
VCH, Weinheim, 2003; d) P. L. Fuchs, Handbook of Reagents for Organic
Synthesis Reagents for Silicon-Mediated Organic Synthesis, Wiley-VCH,
Weinheim, 2011.
[2] For a review on cross-coupling reactions with organosilanes, see: a) S. E.
Denmark, C. S. Regens, Acc. Chem. Res. 2008, 41, 1486. For a review on
allylations and related reactions, see: b) S. E. Denmark, J. Fu, Chem. Rev.
2003, 103, 2763. For a review on Peterson olefinations, see: c) L. F. van
Staden, D. Gravestock, D. J. Ager, Chem. Soc. Rev. 2002, 31, 195. For
a review on Brook rearrangements, see: d) W. H. Moser, Tetrahedron
2001, 57, 2065.
[3] Selected reviews on silicon-based polimers: a) B. K. Teo, X. H. Sun,
Chem. Rev. 2007, 107, 1454; b) F. Ganachaud, S. Boileau, B. Boury, Silicon
Based Polymers, Springer, Heidelberg, 2008; c) P. Jutzi, U. Schubert, Sili-
con Chemistry, Wiley-VCH, Weinhem, 2008; d) A. M. Muzafarov, Silicon
Polymers, Springer, Heidelberg, 2011; e) E. Yilgçr, I. Yilgçr, Prog. Polym.
Sci. 2014, 39, 1165.
[4] For representative examples, see: a) P. D. Lickiss, Adv. Inorg. Chem. 1995,
42, 147; b) S. E. Denmark, L. Neuville, Org. Lett. 2000, 2, 3221; c) S. E.
Denmark, D. Wehrli, Org. Lett. 2000, 2, 565; d) M. Lee, S. Ko, S. Chang, J.
Am. Chem. Soc. 2000, 122, 12011.
Scheme 5. Zinc-catalyzed functionalization of SiÀH bonds in oligosiloxanes
(the value in parenthesis indicates the yield for the three-component reac-
tion). MN =average molecular weight.
[5] Selected examples: a) M. Murata, M. Ishikura, M. Nagata, S. Watanabe, Y.
Masuda, Org. Lett. 2002, 4, 1843; b) A. S. Manoso, P. DeShong, J. Org.
Chem. 2001, 66, 7449; c) S. E. Denmark, R. C. Smith, W.-T. T. Chang, J. M.
Muhuhi, J. Am. Chem. Soc. 2009, 131, 3104.
[6] For a review, see: a) B. Marciniec in Advances in Silicon Science, Springer,
Dordrecht, Netherlands, 2009; b) B. M. Trost, Z. T. Ball, Synthesis 2005,
853.
was selected as a model substrate. Preliminary experiments re-
vealed that the SiÀH bond insertion was feasible, although the
two-component reaction proved superior to the multicompo-
nent version (73% vs. 35%, respectively). Consequently, we
moved to other typical cyclic or linear polysiloxanes (3j and
3k, respectively), which could also be functionalized to obtain
the corresponding functionalized oligosiloxanes 7b–e in good
yields, highlighting the potential of this approach.[23]
[7] For a review on insertion of metal complexes into SiÀH bonds, see:
a) J. Y. Corey, Chem. Rev. 2011, 111, 863.
[8] a) M. P. Doyle, M. A. McKervey, T. Ye, Modern Catalytic Methods for Or-
ganic Synthesis with Diazo Compounds, Wiley, New York, 1998; b) M. P.
Doyle, D. C. Forbes, Chem. Rev. 1998, 98, 911.
In summary, we report the functionalization of SiÀH bonds
through a zinc-catalyzed multicomponent coupling using 1,3-
diones, alk-2-ynals, and silanes, through the in situ generation
of a 2-furyl zinc carbenoid. Inexpensive, low-toxic ZnCl2 was
employed as a single catalyst, promoting a sequence of Knoe-
venagel condensation/enyne cyclization/SiÀH bond insertion in
a self-relay catalytic process. This transformation proceeds
[9] a) J. Nishimura, J. Furukawa, N. Kawabata, J. Organomet. Chem. 1971,
29, 237; b) H. Kondo, Y. Yamanoi, H. Nishihara, Chem. Commun. 2011,
47, 6671.
[10] R. Vicente, J. Gonzµlez, J. Gonzµlez, L. Riesgo, L. A. López, Angew. Chem.
Int. Ed. 2012, 51, 8063; Angew. Chem. 2012, 124, 8187.
[11] a) J. Zhu, H. BienaymØ, Multicomponent Reactions, Wiley-VCH, Weinheim,
2005; b) L. F. Tietze, Domino Reactions: Concepts for Efficient Organic
Synthesis Wiley-VCH, Weinhem, 2014.
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[12] P. S. Rao, R. V. Venkataratnam, Tetrahedron Lett. 1991, 32, 5821.
[13] According to the definition given in: a) N. T. Patil, V. S. Shinde, B. Gajula,
Org. Biomol. Chem. 2012, 10, 211. The transformation can be also de-
fined as an auto-tandem catalysis, according to: b) D. E. Fogg, E. N. dos
Santos, Coord. Chem. Rev. 2004, 248, 2365.
[14] For a brief summary of the screening, see the Supporting Information.
[15] The use of smaller amounts of the silane 3a translated into lower yields
along with an increase of the reaction time. Nevertheless, if desired,
most of the unreacted silane could be recovered by simple distillation
or flash chromatography.
2001, 153; d) D. R. Williams, . I. Morales-Ramos, C. M. Williams, Org.
Lett. 2006, 8, 4393; e) A. B. Smith III, W. S. Kim, R. B. Tong, Org. Lett.
2010, 12, 588; f) L. Gao, X. L. Lin, J. Lei, Z. L. Song, Z. Lin, Org. Lett. 2012,
14, 158; g) J. Lu, Z. L. Song, Y. B. Zhang, Z. B. Gan, H. Z. Li, Angew. Chem.
Int. Ed. 2012, 51, 5367; Angew. Chem. 2012, 124, 5463; h) K. Groll, S. M.
Manolikakes, X. M. du Jourdin, M. Jaric, A. Bredihhin, K. Karaghiosoff, T.
Carell, P. Knochel, Angew. Chem. Int. Ed. 2013, 52, 6776; Angew. Chem.
2013, 125, 6909; i) M. Das, A. Manvar, M. Jacolot, M. Blangetti, R. C.
Jones, D. F. O’Shea, Chem. Eur. J. 2015, 21, DOI: 10.1002/
chem.201500475.
[16] Along with compound 4d, a minor amount (<10%) of 1-(5-(cyclopen-
tylidenemethyl)-2-methylfuran-3-yl)ethan-1-one was also formed. The
formation of this 2-vinylfuran derivative would result from a competitive
1,2-C-H insertion in the postulated zinc carbene intermediate.
[20] For reviews on geminal bimetallic species, see: a) J. A. Marshall, Chem.
Rev. 1996, 96, 31; b) I. Marek, Chem. Rev. 2000, 100, 2887; c) L. Gao, Y.
Zhang, Z. Song, Synlett 2013, 24, 139.
[21] The estimated global production of silicone materials sold as fluids,
elastomers and resins was over 849000 metric tons in 2002, with a 2%
growth rate per year between 1998 to 2002. See: S. Varaprath, D. H.
Stutts, G. E. Kozerski, Silicon Chem. 2006, 3, 79.
[22] For comprehensive recent revisions of applications of polysiloxanes and
silicones, see: a) A. Tiwari, M. D. Soucek, Concise Encyclopedia of High
Performance Silicones, John Wiley & Sons, Hoboken, New Jersey, 2014;
b) K. Kuroda, A. Shimojima, K. Kawahara, R. Wakabayashi, Y. Tamura, Y.
Asakura, M. Kitahara, Chem. Mater. 2014, 26, 211; c) J. J. Chrus´ciel, E. Les´-
niak, Prog. Polym. Sci. 2015, 41, 67.
[23] Compounds 7b–e could be prepared using the three-component pro-
cedure, although in lower yields. See the Supporting Information for
details.
[17] Reaction of ethyl 3-oxobutanoate with alkynal 2a under standard Knoe-
venagel conditions (using catalytic amounts of Mg(ClO4)2 and MgSO4)
led to a 1.2:1 Z:E-mixture of the corresponding enynone. In this case,
isomerization of the enynone or retro-Knoevenagel condensation could
account for the observed yields. On the contrary, attempts to employ
unsymmetric 1,3-diones (R1 =Me; R2 =tBu/Ph) failed due to a competi-
tively faster reduction of the alkynal by the silane with respect to the
required condensation. Unfortunately, attempts to prepare the corre-
sponding enynones by various condensation procedures failed.
[18] Performing the reactions at lower temperatures did not provide better
results. Functionalization of the SiÀH bonds in compounds 4w–z was
not observed under the optimized reaction conditions.
[19] For selected examples on the use of geminal bis(silyl)compounds, see:
a) M. Lautens, P. H. M. Delanghe, Angew. Chem. Int. Ed. Engl. 1995, 33,
2448; Angew. Chem. 1994, 106, 2557; b) G. W. Klumpp, A. J. C. Mierop,
J. J. Vrielink, A. Brugman, M. Schakel, J. Am. Chem. Soc. 1985, 107, 6740;
c) M. D. Hodgson, S. F. Barker, L. H. Mace, J. R. Moran, Chem. Commun.
Received: March 24, 2015
Published online on May 26, 2015
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