Initiation and termination mode of enyne cross-metathesis and metallotropic [1,3]-shift controlled by remote substituents

Article abstract of DOI:10.1021/ja1020525

The cross-metathesis of terminal alkyne and alkene using Ru-based Grubbs catalyst generally undergoes α-insertion. In this study, excellent control over α- and β-insertion of ruthenium alkylidene into terminal alkynes has been achieved by using a substituent at a remote site from the reaction center. While the origin of this regioselectivity of insertion and metallotropic shift remains to be established, the trend indicates that the α-insertion with a concomitant metallotropic shift is favored with small substituents whereas the β-insertion without a metallotropic shift is favored with bulky substituents such as tert-butyl and trialkyl silyl groups.

Full text of DOI:10.1021/ja1020525

Published on Web 06/15/2010
Initiation and Termination Mode of Enyne Cross-Metathesis and Metallotropic
[1,3]-Shift Controlled by Remote Substituents
Sang Young Yun, Kung-Pern Wang, Mansuk Kim,† and Daesung Lee*
Department of Chemistry, UniVersity of Illinois at Chicago, 845 West Taylor Street, Chicago, Illinois 60607-7061
Received March 10, 2010; E-mail: dsunglee@uic.edu
Scheme 1. R- and ꢀ-Insertion Mode Selectivity
Control over the regio- and stereoselectivity in enyne cross-
metathesis (CM) is a challenging problem, and thus it represents a
fundamentally important area of investigation.1,2 The CM of diyne
A and alkene using Ru-based Grubbs catalyst 13 is known to
undergo R-insertion, leading to alkylidenes of type B and thus C.4,5
To the best of our knowledge, ꢀ-insertion of a ruthenium-based
Grubbs type complex to generate a vinyl akylidene D from A has
not been reported.6 On the other hand, Schrock type molybdenum
imido-alkylidene complex 2 prefers ꢀ-insertion, generating alky-
lidenes D and thus E.7 Intermediates C and E derived from the R-
and ꢀ-insertion would ultimately deliver CM products F and H,
respectively. In cyclopolymerization of 1,6-diyne A,8 the ring size
of the repeating unit significantly affects polymer properties,9
rendering extensive investigation into the regioselective insertion.
Investigation by Buchmeiser4 and Schrock7 using variants of 1 and
2 to obtain homogeneous polymers G and H are most notable in
this regard. Recently, enyne ring-closing metathesis (RCM) by
molybdenum alkylidenes with pyrrolide ligands generated diene I
via the ꢀ-insertion.10
to control the mode of insertion. Moreover, the subsequent
metallotropic shift step seems to be directly coupled with the
initiation event: a metallotropic shift upon R-insertion, no
metallotropic shift upon ꢀ-insertion. In this Communication, we
report the result of our investigation on this unprecedented
control over the regioselectivity of initiation and termination in
tandem enyne CM-metallotropic shift processes.
The generality of the regioselectivity observed in Scheme 1 was
further explored by changing the steric and electronic factors on
the alkyne and alkene substrates (Table 1). The CM of 3a-e with
alkenes 4a-e resulted in the exclusive formation of five-membered
ring products (5aa, 5ab, 5ba, 5ca, 5da, 5ea, 5ec, 5ed, 5ee) in good
yields and predicted regio- and stereoselectivity (entries 2-9).
Contrary to tertiary alcohol 3e, however, its acetate and benzyl as
well as silyl ether derivatives behave differently. The acetate 3f
did not afford 5fa (entry 10); instead most of the starting material
was recovered unchanged.13 The benzyl and silyl ethers 3g and 3h
afforded mixtures of five- and six-membered ring products (5ga/
6ga ) 1:1, 5he/6he ) 1:3), probably because of the stericallyl-
hindered nature of these groups compared to the tertiary alcohol.
The CM of tert-butyl group-containing substrate 3i gave a mixture
of 5ia and 6ia with a 1:4 ratio, which further supports this
hypothesis (entry 13). Interestingly, reaction of triethylsilyl-
substituted substrate 3j with ethylene (4f) afforded a mixture of
5jf14 and 6jf (entry 14) but with other alkenes such as 1-octene
and TBS-protected allyl alcohol provided exclusively 6ja and 6jc
(entries 16 and 17). Other silyl group-substituted substrates 3k and
3l also provided six-membered ring products 6la, 6ma, and 6mb
with slightly reduced yields (entries 18-20).
From Table 1, it is clear that the R-insertion and subsequent
metallotropic [1,3]-shift is favorable with sterically unhindered
substituents, whereas the hindered ones promote ꢀ-insertion without
a metallotropic shift. Yet, it is not obvious how these substituents
exert their influence to the mode of initiation. To gain more insight
into these issues, we explored the reaction of 7a and 7b that have
a longer tether length between the initiating alkyne and diynes
(Scheme 2). Contrary to the selectivity trend with 3a-m, both
substrates 7a and 7b exhibited identical R-insertion, affording 8a
and 8b, where the initiation event is not coupled with the
termination. These results suggest that the distance between the
In conjunction with divergent metallotropic [1,3]-shift11 behavior
of conjugated multiyne,12 we envisioned that the tandem process
involving enyne CM of 3 followed by RCM and a metallotropic
[1,3]-shift sequence would provide access to novel molecular
structures with diverse patterns of unsaturation (Scheme 1). Initial
studies revealed that the regio- and stereochemical outcome of the
products critically depends on the nature of the substituent at the
terminating end. For example, the reaction of 3a bearing a phenyl
substituent on the diyne exclusively afforded 5aa (E/Z ) 10:1) with
a catalytic amount of 1 and 1-octene (4a). In stark contrast, 3j
carrying a triethylsilyl substituent proceeded with exclusive R-inser-
tion to produce 6ja as a single regio- and stereoisomer. The other
isomers 6aa and 5ja were not detected. It is quite striking that
the substituent at the diyne remote from the initiation site seems
† Current address: Samsung Cheil Industries Inc., Gocheon-Dong 332-2, Uiwang-
Si, Gyeonggi-Do, Korea, 437-711.
9
8840 J. AM. CHEM. SOC. 2010, 132, 8840–8841
10.1021/ja1020525  2010 American Chemical Society

C O M M U N I C A T I O N S
Table 1. Mode Selectivity Controlled by Remote Substituentsa
reversibly, the putative alkylidene species should be trapped by
the ring-closing termination to give respective products 10a and
10b. However, contrary to 3g that gave a 1:1 mixture of five- and
six-membered ring products 5ga and 6ga, the reaction of 9
generated only 10a (65%). This result suggests that, at least for 9,
the initiation step should be selective for R-insertion. The discrep-
ancy between 3g and 9 in product distribution must be due to the
difference in their structures although seemingly minor.
entry
3
R1
4
R2
product
yield (%)b
In conclusion, we have documented the first examples of
ꢀ-insertion of Grubbs-type ruthenium alkylidene into terminal
alkynes controlled by a bulky substituent at a remote site from the
reaction center. While the origin of this regioselective insertion and
metallotropic shift remains to be established, direct influence of
the substituent on the initiation process through the interaction of
the diyne moiety with the ruthenium center seems feasible.
This unprecedented regioselective insertion of a Ru-alkylidene,
especially when it is in tandem with a metallotropic [1,3]-shift,
would broaden the scope of enyne metathesis as a powerful tool to
synthesize a new class of multiply conjugated unsaturated molecules
containing alternating double and triple bonds.
1
2
3
4
5
6
7
8
a
Ph
a
b
a
a
a
a
c
d
e
a
a
e
a
f
a
c
a
a
a
b
(CH2)5CH3 5aa (10:1)c
CH2Ph 5ab (1:0)
(CH2)5CH3 5ba (3:1)
5ca (10:1)
5da (4:1)
5ea (3:1)
CH2OTBS 5ec (3:1)
81
75
70
80
59
91
90
86
85
a
b
c
CH2OBn
CH2OAc
dd CH2OAc
e
e
e
e
f
g
h
i
C(CH3)2(OH)
CH2TMS
CH2OAc
(CH2)5CH
5ed (2:1)
5ee (2:1)
-
9
e
10
11
12
13
14
15
16
C(CH3)2(OAc)
C(CH3)2(OBn)
C(CH3)2(OTBS)
t-Bu
-
5ga (1:1)f 6ga
5he (1:3)f 6he
63
70
69
90
61
50
CH2OAc
(CH2)5CH3 5ia
H
(1:4)f 6ia
j
j
j
SiEt3
5jf
(2:1)g 6jf
(CH2)5CH3
CH2OTBSh
(CH2)5CH3
6ja
6jc
-
Acknowledgment. We thank UIC for financial support for this
work.ThemassspectrometryfacilityatUIUCisgreatlyacknowledged.
17 ki
18
19
20
-
j
l
m
m
Si(CH3)2Bn
Si(i -Pr)3
6la
69
72
52
Supporting Information Available: General procedures, charac-
terization for representative compounds. This material is available free
of charge via the Internet at http://pubs.acs.org.
6ma
6nb
CH2Ph
a Reactions performed with 8 mol % Grubbs II catalyst (1) at 40 °C
in CH2Cl2 for 1-2 h. b Total yield (5 + 6). c E/Z ratio. d X ) NTs.
e Ruthenium complex formed. f Ratio of 5 and 6. g Ratio of 5jf (in
Scheme 1) and 6jf (see Supporting Information). h Allyl acetate and
References
(1) Reviews: (a) Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54, 4413. (b)
Fu¨rstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012. (c) Schrock, R. R.;
Hoveyda, A. H. Angew. Chem., Int. Ed. 2003, 42, 4592. (d) Deiters, A.;
Martin, S. F. Chem. ReV. 2004, 104, 2199. For enyne metathesis: (e)
Giessert, A. J.; Diver, S. T. Chem. ReV. 2004, 104, 1317. (f) Poulsen, C. S.;
Madsen, R. Synthesis 2003, 1. (g) Mori, M. In Handbook of Metathesis;
Grubbs, R. H., Ed.; Wiley-VCH: Weinheim, Germany, 2003; Vol. 2, pp
176-204.
allyltrimethylsilane gave uncharacterizable products. i X
j Uncharacterizable material formed.
) NTs.
Scheme 2. CM with Longer Tethered Triynes
(2) For regio-and steroselective cross enyne metathesis: (a) Kim, M.; Park, S.;
Maifeld, S.; Lee, D. J. Am. Chem. Soc. 2004, 126, 10242. (b) Kim, M.;
Lee, D. Org. Lett. 2005, 7, 1865.
(3) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953.
(4) (a) Kumar, P. S.; Wurst, K.; Buchmeiser, M. R. J. Am. Chem. Soc. 2009,
131, 387. (b) Krause, J. O.; Zarka, M. T.; Anders, U.; Weberskirch, R.;
Nuyken, O.; Buchmeiser, M. R. Angew. Chem. 2003, 115, 6147. (c) Krause,
J. O.; Nuyken, O.; Buchmeiser, M. R. Chem.sEur. J. 2004, 10, 2029. (d)
Vygodskii, Y. S.; Shaplov, A. S.; Lozinskaya, E. I.; Vlasov, P. S.;
Malyshkina, I. A.; Gavrilova, N. D.; Kumar, P. S.; Buchmeiser, M. R.
Macromolecules 2008, 41, 1919.
(5) Stragies, R.; Schuster, M.; Blechert, S. Chem. Commun. 1999, 237.
(6) Mechanistic studies of enyne metathesis: (a) for
a computational
study: Lippstreu, J. J.; Straub, B. F. J. Am. Chem. Soc. 2004, 127, 7444.
(b) for coordination of alkene vs alkyne: Sohn, J.-H.; Kim, K. H.; Lee,
H.-Y.; No, Z. S.; Ihee, H. J. Am. Chem. Soc. 2008, 130, 16506. (c) for
initiation study with isotopically labeled substrate: Lloyd-Jones, G. C.;
Margue, R. G.; de Vries, J. G. Angew. Chem., Int. Ed 2005, 44, 7442. (d)
for a kinetic study: Diver, S. T.; Galan, B. R.; Giessert, A. J.; Keister,
J. B. J. Am. Chem. Soc. 2005, 127, 5762.
Scheme 3. Intramolecular Trapping of the Putative Intermediate
(7) (a) Fox, H. H.; Schrock, R. R. Organometallics 1992, 11, 2763. (b)
Schattenmann, F. J.; Schrock, R. R.; Davis, W. M. J. Am. Chem. Soc. 1996,
118, 3295.
(8) (a) Choi, S.-K.; Gal, Y.-S.; Jin, S.-H.; Kim, H. K. Chem. ReV. 2000, 100,
1645. (b) Lam, J. W. Y.; Tang, B. Z. J. Polym. Sci. 2003, 41, 2607. (c)
Buchmeiser, M. R. AdV. Polym. Sci. 2005, 176, 89.
(9) Krause, J. O.; Wang, D.; Anders, U.; Weberskirch, R.; Zarka, M. T.;
Nuyken, O.; Ja¨ger, C.; Haarer, D.; Buchmeiser, M. R. Macromol. Symp.
2004, 217, 179.
(10) Lee, Y.-J.; Schrock, R. R.; Hoveyda, A. H. J. Am. Chem. Soc. 2009, 131,
10652.
(11) A review of metallotropic shift: (a) Kim, M.; Lee, D. Org. Biomol. Chem.
2007, 5, 3418. Synthetic applications: (b) Cho, E. J.; Lee, D. Org. Lett.
2008, 10, 257. (c) Li, J.; Miller, R. L.; Lee, D. Org. Lett. 2009, 11, 571.
(12) (a) Yun, S. Y.; Kim, M.; Lee, D.; Wink, D. J. J. Am. Chem. Soc. 2009,
131, 24. (b) Kim, M.; Miller, R. L.; Lee, D. J. Am. Chem. Soc. 2005, 127,
12818. (c) Wang, K.-P.; Yun, S. Y.; Lee, D.; Wink, D. L. J. Am. Chem.
Soc. 2009, 131, 15114.
initiating alkyne and the diyne moiety is important for the
substituents to influence the initiation event, and the metallotropic
shift depends on the nature of the substituent on the diyne and not
the mode of initiation.
The possibility of equilibration between intermediates was
explored with probe 9, a close analogue of 3g (Scheme 3). If the
intermediates from the R- and ꢀ-insertion pathways are formed
(13) Complete consumption of 3f was achieved in the presence of a stoichio-
metric amount of 1. See Supporting Information.
(14) The CM of 6jf and 1-octene did not occur under the reaction conditions.
JA1020525
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