Novel synthesis of cyclic alkenylboronates via ring-closing metathesis [12]

Full text of DOI:10.1021/ja980958i

J. Am. Chem. Soc. 1998, 120, 7995-7996
7995
of vinylboronates to undergo oxidation furnishes a route for the
preparation of ketones.10 In this communication, we disclose that
five-, six-, and seven-membered carbocyclic and heterocyclic
alkenylboronates are synthesized in high yield via metathesis of
acyclic olefinic boronates.
Novel Synthesis of Cyclic Alkenylboronates via
Ring-Closing Metathesis
Johanne Renaud* and Ste´phane G. Ouellet
Our initial attempts were directed toward the metathesis of
dialkenylboronic acid 3 (eq 2). Much to our delight, upon
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ReceiVed March 23, 1998
The versatility and synthetic applicability of the ring-closing
metathesis (RCM) reaction in the construction of functionalized
carbocycles and heterocycles has recently been demonstrated by
a number of groups.1,2 The emergence of the well-defined
transition metal catalysts 13 and 2a,b4,5 has greatly expanded the
treatment of 3 with catalyst 2b at room temperature in benzene
(0.002 M), cyclization occurred smoothly to provide 1-cyclohex-
enylboronic acid (4) in 54% yield. In contrast, molybdenum
catalyst 1 did not furnish the required material in significant
quantity. Despite our effort to increase the efficiency of this
cyclization reaction, the yield was not further improved. How-
ever, when the dialkenylboronic ester 5 was treated with catalyst
2b (4 mol %), cycloalkene 6 was generated in 72% yield (eq 3).
scope and utility of this method. Of distinct significance is the
high tolerance of the alkylidene complexes 2a and 2b to
commonly encountered functional groups. Various dienes, bear-
ing substituents in the tether linking the olefins, have been shown
to undergo metal alkylidene-catalyzed cyclizations.1 Notably
however, RCM has predominantly been exploited for the prepara-
tion of cyclic entities containing unsubstituted alkene moieties.
In cases where the olefin is functionalized, substituents encoun-
tered are either carbon or oxygen.1,6-8 We were intrigued by the
possibility of employing such a strategy to access boron-
substituted cyclic olefins (eq 1). Alkenylboronic esters and acids
The ease of isolation and handling of the dienylboronic esters
compared to that of the corresponding acids directed our effort
toward the utilization of the former substances in RCM reactions.
Further investigations of the reaction conditions revealed that the
transformation of 5 into 6 was also accomplished very efficiently
in the presence of the commercially available catalyst [bis(tricy-
clohexylphosphine)benzylidene]ruthenium dichloride (2a). After
purification of the crude material on neutral silica gel,11 the desired
cyclic vinylboronate 6 was obtained in an excellent 90% yield
(Table 1, entry 1). These are the first examples of ruthenium-
catalyzed RCM of substituted dienes into trisubstituted cyclic
olefins bearing substituents other than carbon.
are highly valuable synthetic intermediates, particularly with
regards to carbon-carbon bond formation through palladium-
catalyzed Suzuki coupling reactions.9 Moreover, the propensity
To establish the generality of this transformation, a series of
carbon-, oxygen-, and nitrogen-containing acyclic dienylboronates
was synthesized as summarized in Scheme 1. Reaction of
(1) For recent reviews on olefin metathesis, see: (a) Grubbs, R. H.; Chang,
S. Tetrahedron 1998, 54, 4413. (b) Armstrong, S. K. J. Chem. Soc., Perkin
Trans. 1 1998, 371. (c) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed.
Engl. 1997, 36, 2037.
Scheme 1. Synthesis and Ring-Closing Metathesis of Acyclic
Dialkenylboronatesa
(2) For earlier reports on RCM, see: (a) Fu, G. C.; Grubbs, R. H. J. Am.
Chem. Soc. 1992, 114, 7324. (b) Fu, G. C.; Grubbs, R. H. J. Am. Chem. Soc.
1992, 114, 5426.
(3) (a) Bazan, G. C.; Oskam, J. H.; Cho, H.-N.; Park, L. Y.; Schrock, R.
R. J. Am. Chem. Soc. 1991, 113, 6899. (b) Schrock, R. R.; Murdzek, J. S.;
Bazan, G. C.; Robbins, J.; DiMare, M.; O’Regan, M. J. Am. Chem. Soc. 1990,
112, 3875.
(4) (a) Nguyen, S. T.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1993,
115, 9858. (b) Nguyen, S. T.; Johnson, L. K.; Grubbs, R. H.; Ziller, J. W. J.
Am. Chem. Soc. 1992, 114, 3974.
(5) (a) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996,
118, 100.
a Reagents and conditions: (a) tBuLi, Et2O, -78 °C; 2-(isopropyloxy)-
4,4,5,5-tetramethyl-1,3,2-dioxaborolane (7), -78 °C to room temperature;
H2O. (b) Grubbs’ catalyst (2a), benzene, room temperature. Boc ) N-(tert-
(6) Vinyl halides and dienynes bearing substituents such as TMS, Cl, Br,
I, and SnBu3 at their alkyne terminus do not undergo RCM. See: (a) Kirkland,
T. A.; Grubbs, R. H. J. Org. Chem. 1997, 62, 7310. (b) Kim, S.-H.; Zuercher,
W. J.; Bowden, N. B.; Grubbs, R. H. J. Org. Chem. 1996, 61, 1073.
(7) Disubstituted cyclic vinylsilyl ethers, where the silyl group is embedded
within the ring, were prepared through RCM catalyzed by 1. See: Chang, S.;
Grubbs, R. H. Tetrahedron Lett. 1997, 38, 4757.
t
butoxycarbonyl); Bn ) CH2Ph; TBS ) BuMe2Si.
2-(isopropyloxy)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (7)12 with
vinyllithium intermediates, generated from the corresponding
(8) For RCM of olefinic enol ethers, mediated by 1 see: (a) Clark, J. S.;
Kettle, J. G. Tetrahedron Lett. 1997, 38, 123. (b) Fujimura, O.; Fu, G. C.;
Grubbs, R. H. J. Org. Chem. 1994, 59, 4029. (c) Fu, G. C.; Grubbs, R. H. J.
Am. Chem. Soc. 1993, 115, 3800.
(9) Miyaura, N.; Suzuki, A. Chem. ReV. 1995, 95, 2457.
S0002-7863(98)00958-5 CCC: $15.00 © 1998 American Chemical Society
Published on Web 07/24/1998

7996 J. Am. Chem. Soc., Vol. 120, No. 31, 1998
Communications to the Editor
vinylic bromides13 by lithium-halogen exchange, furnished the
required dienylboronate precursors. Subjection of these olefins
to RCM conditions provided the corresponding borate-substituted
carbocycles and heterocycles. The results of this study are listed
in Table 1.
employed to minimize the formation of dimer, resulting from
cross-metathesis, when the reaction rates were slow. In the
carbocyclic series, cyclization of the five-membered ring precursor
cleanly furnished the cyclopenteneboronic ester in 84% yield after
118 h (entry 2). Under similar conditions, RCM of the six-
membered ring diene precursors provided readily the cyclohex-
eneboronates, within 6-15 h, in excellent yields (entries 1, 3,
Table 1. Ring-Closing Metathesis of Acyclic Olefinic Boronatesa
and 4). The seven-membered ring systems were synthesized in
77% and 76% yields, respectively (entries 5 and 6), but required
prolonged reaction times (76 and 118 h). In each of the latter
two reactions, dimeric products, resulting from intermolecular
metathesis of the less substituted alkene, were also isolated. In
the heterocyclic series, conversions of dialkenylboronates into
five- and six-membered oxygen and nitrogen heterocycles bearing
a vinylboronate moiety were achieved in yields ranging from 66%
to 85% (entries 7-10). Interestingly, while the five-membered
oxacycle formed in 5 h (entry 7), extended reaction times were
required for the preparation of the remaining heterocyclic
compounds. The reasons for the difference in reactivity of the
various dienes are unclear. The slower rates of ring closure
mayresult from the formation of intermediate ruthenium com-
plexes, formed ruthenium carbene center.14 It seems likely that
the pinacolboronate oxygens are involved in the chelation since,
in a few instances, related unsubstituted alkenes have been shown
to undergo RCM much faster. Moreover, it appears that, in
addition to the presence of the boronate functional group, a donor
center (ether or benzyloxy oxygen) is required to reduce the rate
of the reaction. Thus, the presence and the location of both
functionalities within the diene and their interaction with the
ruthenium alkylidene center may be responsible for the variations
in the rates of cyclization. Alternatively, conformational bias of
the diene could retard ring closure. Further studies to understand
the origin of this phenomenon are underway.
In summary, we have demonstrated that the RCM reaction is
a practical and reliable procedure for the synthesis of trisubstituted
cyclic vinylboronates. The work presented in this communication
has established a novel strategy for the assembly of hitherto
unexplored frameworks through ruthenium carbene-promoted
cyclization, and further broadens the scope and synthetic utility
of this powerful reaction.
Acknowledgment. NSERC is thanked for an industrial undergraduate
scholarship to S.G.O. Dr. R. Zamboni and Dr. C. Black are acknowledged
for their valuable comments regarding this paper.
Supporting Information Available: General experimental procedures
and characterization data for acyclic and cyclic vinylboronates (22 pages,
print/PDF). See any current masthead page for ordering information and
Web access instructions.
JA980958I
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