Borostannylation of alkynes and enynes. Scope and limitations of the reaction and utility of the adducts

Article abstract of DOI:10.1021/ol100824f

The utility of the hetero-bismetallating reagent 1,3-dimethyl-2- trimethylstannyl-2-bora-1,3-diazacyclopentane (1) has not been fully realized because of the hydrolytic instability of the products derived from catalyzed vicinal syn-additions to alkynes. The isolation of a variety of such adducts derived from alkynes (and also from hitherto unreported additions to 1,3-enynes) as stable boron pinacolates is reported. Examples of the applications of resulting products in tandem cross-coupling reactions and as dienes in Diels-Alder reactions are illustrated.

Full text of DOI:10.1021/ol100824f

ORGANIC
LETTERS
2010
Vol. 12, No. 11
2622-2625
Borostannylation of Alkynes and
Enynes. Scope and Limitations of the
Reaction and Utility of the Adducts
Ramakrishna Reddy Singidi and T. V. RajanBabu*
Department of Chemistry, The Ohio State UniVersity, 100 West 18th AVenue,
Columbus, Ohio 43210
rajanbabu.1@osu.edu
Received April 11, 2010
ABSTRACT
The utility of the hetero-bismetallating reagent 1,3-dimethyl-2-trimethylstannyl-2-bora-1,3-diazacyclopentane (1) has not been fully realized
because of the hydrolytic instability of the products derived from catalyzed vicinal syn-additions to alkynes. The isolation of a variety of such
adducts derived from alkynes (and also from hitherto unreported additions to 1,3-enynes) as stable boron pinacolates is reported. Examples
of the applications of resulting products in tandem cross-coupling reactions and as dienes in Diels-Alder reactions are illustrated.
While exploring the applications of hetero-bismetallative
cyclization of R,ω-diynes using 1,3-dimethyl-2-trimethyl-
stannyl-2-bora-1,3-diazacyclopentane 1 (eq 1) in the synthesis
of highly functionalized dibenzocyclooctadienes,1 it became
apparent that except for low molecular weight adducts where
the products can be isolated by distillation, or in rare cases
where they are crystalline, the hydrolytic instability of the
primary [BSn] adducts severely limits the utility of this
otherwise useful reagent.2 Further impetus for work in the
area came from our recent recognition that, despite the
extreme sensitivity to moisture and difficulties in its prepara-
tion, this reagent could have a much broader substrate scope
and improved selectivity in its reactions as compared to the
more well-known silylstannanes.3 Even though both reagents
undergo regio- and stereoselective 1,2-addition to terminal
alkynes, giving products in which the stannyl residue is
attached to the internal carbon, only the [BSn] reagent reacts
with internal alkynes. In this paper, we provide examples of
a simple protocol for the isolation of the borylstannyl alkenes
derived from acetylene, mono- and disubstituted alkynes, and
enynes. Also illustrated are examples of applications of the
products derived from these reactions, including tandem
Stille/Suzuki coupling reactions and the use of a highly
(1) Singidi, R. R.; RajanBabu, T. V. Org. Lett. 2008, 10, 3351.
(2) Palladium-catalyzed additions of 1 to alkynes including reactions
that lead to carbocyclic 1,2-bisalkylidenes were initailly reported by Tanaka
et al. See: (a) Onozawa, S.-y.; Hatanaka, Y.; Sakakura, T.; Shimada, S.;
Tanaka, M. Organometallics 1996, 15, 5450. (b) Onozawa, S.-y.; Hatanaka,
Y.; Choi, N.; Tanaka, M. Organometallics 1997, 16, 5389. See also: (c)
Weber, L.; Wartig, H. B.; Stammler, H. G.; Stammler, A.; Neumann, B.
Organometallics 2000, 19, 2891. For the preparaion of the reagent 1, see:
(d) Niedenzu, K.; Rothgery, E. F. Synth. React. Inorg., Met.-Org. Chem.
1972, 2, 1. For a review of 1,3-dimethyl-2-trimethylstannyl-2-bora-1,3-
diazacyclopentane, see: (e) Tanaka, M. In Encyclopedia of Reagents for
Organic Synthesis; Paquette, L. A., Ed.; John Wiley: New York, 2004.
(3) (a) Chenard, B. L.; Laganis, E. D.; Davidson, F.; RajanBabu, T. V.
J. Org. Chem. 1985, 50, 3666. (b) Warren, S.; Chow, A.; Fraenkel, G.;
RajanBabu, T. V. J. Am. Chem. Soc. 2003, 125, 15402. (c) Kumareswaran,
R.; Shin, S.; Gallou, I.; RajanBabu, T. V. J. Org. Chem. 2004, 69, 7157.
(d) Apte, S.; Radetich, B.; Shin, S.; RajanBabu, T. V. Org. Lett. 2004, 6,
4053. (e) Trimethylsilyltributylstannane: RajanBabu, T. V.; Shin, S. In
Encyclopedia of Reagents for Organic Synthesis; Paquette, L. A., Ed.; John
Wiley: New York, 2005.
10.1021/ol100824f  2010 American Chemical Society
Published on Web 05/11/2010

functionalized adduct from an enyne as a diene in a
Diels-Alder reaction.
Table 1. Borostannylation of Alkynes Using 1 Followed by
Dioxaborolidene Formationa
In a typical example, we find that the crude primary
product (3a) from 3-benzyloxy-1-propyne (2a) when treated
with pinacol in the presence of p-toluenesulfonic acid gives
a dioxaborolidine (4a) that can be isolated in high yield
(Scheme 1).4 Thus addition of 1 to 2a at room temperature
Scheme 1. Borostannylation of an Alkyne
in the presence of 0.05 equiv of PdCl2·(Ph3P)2 gives the
expected adduct (3a) in excellent conversion as judged by
in situ NMR spectroscopy. After 6 h at room temperature, a
solution of 1.2 equiv of pinacol dissolved in benzene and
1.2 equiv of solid p-toulenesulfonic acid are added, and the
reaction is stirred for an additional 2 h.5,6 The reaction is
quenched by addition of triethylamine (1.6 equiv), and
product 4a is isolated by column chromatography on silica
gel after concentration. The Z-configuration of product 4a
can be easily established by NOE measurements. Other
examples of these transformations are shown in Table 1. In
general, excellent regio- and stereoselectivities are observed
for these reactions, and yields are surprisingly good for the
generation of such a functionalized alkene. The sequence of
a See Scheme 1 for procedure. b Isolated by column chromatography.
c Use of PdCl2(CH3CN)2/P(But)3 (60 °C, 12 h) gives a ratio of 4h1/4h2 )
94:6.
(4) Bromoboration of an alkyne followed by reaction of the resulting
dibromobora-alkene with N,N′-dimethylethylenediamine or pinacol also
gives adducts similar to 3 and 4. See: (a) Lallemand, J.-Y.; Six, Y.; Ricard,
L. Eur. J. Org. Chem. 2002, 503. (b) Wang, C.; Tobrman, T.; Xu, Z.;
Negishi, E.-i. Org. Lett. 2009, 11, 4092. (c) For another reference to the
formation and reactions of borostannylalkenes, see: Lhermitte, F.; Carboni,
B. Synlett 1996, 377.
reactions, especially the acid-catalyzed pinacolate formation,
is tolerated by various propargylic substituents such as a
benzyl ether (entry 1), a trimethylsilyl group (entry 4), and
even a triphenylstannane moiety (entry 5).
Disubstitued alkynes also give the corresponding Z-adducts
in very good to excellent yields. Diphenylacetylene gives
the Z-product 4f in 84% yield (entry 6). 1-Phenylpropyne
gave a mixture of products in a ratio of 79:11 with the stannyl
moiety occupying the benzylic position as the major isomer.
1-Phenylbutyne also shows comparable regioselectivity
(5) See Supporting Information for experimental details and full
characterization of the products.
(6) For examples of 2,5-azaborolidine to 2,5-oxaborolidine conversions,
see: (a) Biffar, W.; No¨th, H.; Schwertho¨ffer, R. Liebigs Ann. Chem. 1981,
2067. (b) Suginome, M.; Yamamoto, A.; Murakami, M. Angew. Chem.,
Int. Ed. 2005, 44, 2380. (c) Onozawa, S. y.; Hatanaka, Y.; Tanaka, M.
Tetrahedron Lett. 1998, 9043
.
Org. Lett., Vol. 12, No. 11, 2010
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(entry 8). An examination of ligand effects5 revealed that
use of PdCl2(CH3CN)2/P(But)3 (60 °C, 12 h) gave an
improved regioselectivity (94:6), albeit with decreased overall
yield (75%).
Table 2. Borostannylation of Enynesa
Acetylene itself undergoes facile borostannylation at
ambient pressure and temperature to give a 2:1 adduct 5 in
86% yield and with very high regio- and stereoselectivity
(Scheme 2).7 The ZZ-configuration of the double bonds can
Scheme 2
.
Borostannylation of Acetylene at Ambient
Temperature and Pressure
be deduced from the coupling constants of the alkene protons
(J12 ) 12.0-13.5 Hz). The corresponding EE-diastereomer
has been described in the literature,8 and it exhibits J12 values
in the range of 15.2-18.0 Hz. A similar dimerization reaction
has been observed in the Ni-catalyzed reactions of
Me2(Ph)Si-B(pinacolate) with terminal alkynes.9
Borostannylation of Enynes. Pd-catalyzed borostanny-
lation of enynes has not been disclosed in the literature. This
class of substrates undergoes the addition reaction with
surprisingly high chemo-, regio-, and stereoselectivity. No
complication from the adjacent alkene has been noted. Under
the standard conditions described earlier, a variety of 1,3-
enynes give very good yields of highly functionalized
bismetalated dienes. Only one isomer (Z, with a terminal
boronate) is detected by NMR (selectivity >19:1). Typical
examples are shown in Table 2. Among the enynes studied,
2-phenylbuta-1-ene-3-yne (6e) alone gave an unsatisfactory
yield.
a See Scheme 1 for procedure. b Isolated by column chromatography.
important natural products.10 The dienes we disclose have
different configurations and are not accessible by previously
reported routes.
A prototypical application of the 1,2-borylstannyl alkene
is illustrated in Scheme 3. Adduct 4a carrying an allylic
Applications. The bismetalated alkenes and dienes are
valuable intermediates, providing rapid access to stereode-
fined alkenes and polyalkenes, largely because of the power
of cross-coupling reactions such as Stille and Miyaura-Suzuki
reactions. The vinyl stannyl group can also be replaced by
a bromine or iodine, and the resulting products could serve
as electrophilic partners in yet other cross-coupling
reactions.4b The value of 1,4-disubstituted borylstannyl dienes
has been amply demonstrated by Coleman, who used these
compounds to prepare the polyene side chains of several
Scheme 3
.
Tandem Stille/Suzuki Reactions of a Borylstannyl
Alkene
benzyloxy substituent undergoes Stille reaction with iodo-
benzene at room temperature giving an 85% yield of 8. The
resulting boronate is an excellent substrate for a Suzuki
(7) A similar reaction using a Pd-bisphosphite catalyst has been
described in the patent literature. Onozawa, S. y.; Tanaka, M. Jpn. Kokai
Tokkyo Koho 2003, 6692. However, experimental and characterization
details are not readily available. Trimethylsilyltributylstannane undergoes
the expected Pd-catalyzed 1,2-syn-addition to acetylene. See: Murakami,
M.; Matsuda, T.; Itami, K.; Ashida, S.; Terayama, M. Synthesis 2004, 1522.
(8) Coleman, R. S.; Walczak, M. C. Org. Lett. 2005, 129, 2289.
(10) (a) Coleman, R. S.; Lu, X.; Modolo, I. J. Am. Chem. Soc. 2007,
129, 3826. (b) Coleman, R. S.; Walczak, M. C.; Campbell, E. L. J. Am.
Chem. Soc. 2005, 127, 16038.
(9) Suginome, M.; Matsuda, T.; Ito, Y. Organometallics 1998, 17, 5233.
2624
Org. Lett., Vol. 12, No. 11, 2010

coupling with 4-iodobromobenzene, giving a trisubstituted
alkene 9 in over 90% yield. As expected, these reactions
proceed with excellent stereoselectivity.
from borostannylation of alkynes and enynes using a
capricious yet very reactive and selective reagent. This
procedure preserves the two vinyl metal moieties, still
enabling stepwise bidirectional elaboration based on the
intrinsically different reactivities of the respective
carbon-metal bonds.
Finally, the utility of the bismetalated dienes for Diels-
Alder reaction is illustrated with the example of 7a in eq 2.
Formation of a nearly quantitative yield of the endo-adduct
10 suggests that these dienes are quite reactive even with
the electron-withdrawing boron substituent.11 Many ways of
further elaborating these highly functionalized molecules,
including the powerful Vaultier sequence (Diels-Alder
followed by allyl boronation),11a can be envisioned.
Acknowledgment. Financial assistance for this research
by NSF (CHE-0610349) and NIH (General Medical Sci-
ences, R01 GM075107) is gratefully acknowledged.
Supporting Information Available: Full experimental
1
details for the preparation of precursors 6a-6e and H and
13C NMR of all new compounds. This material is available
free of charge via the Internet at http://pubs.acs.org.
OL100824F
(11) For Diels-Alder reactions of boron-substituted 1,3-dienes, see: (a)
Vaultier, M.; Truchet, F.; Carboni, B.; Hoffmann, R. W.; Denne, I.
Tetrahedron Lett. 1987, 28, 4169. (b) Gao, X.; Hall, D. G. Tetrahedron
Lett. 2003, 44, 2231. See also ref 4a. A recent review of the chemistry
of boron and silicon-substituted dienes: (c) Welker, M. E. Tetrahedron
2008, 64, 11529. (d) Toure, B. B.; Hall, D. G. Chem. ReV. 2009, 109,
4439.
In summary, we report a simple procedure for the
derivatization of hydrolytically unstable primary adducts
Org. Lett., Vol. 12, No. 11, 2010
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