Ruthenium-catalyzed enyne metathesis of acetylenic boronates: A concise route for the construction of cyclic 1,3-dienylboronic esters

Article abstract of DOI:10.1002/1521-3773(20000901)39:17<3101::AID-ANIE3101>3.0.CO;2-I

The operationally simple and highly efficient metathesis of enynes bearing an acetylenic dioxaborolane moiety provides straightforward access to carbocyclic and heterocyclic 1,3-dienyl-2-boronates [Eq. (1)]. Dienes of this class readily undergo Diels-Alder cycloaddition reactions with high regio- and stereoselectivity.

Full text of DOI:10.1002/1521-3773(20000901)39:17<3101::AID-ANIE3101>3.0.CO;2-I

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‡
127.78, 128.31, 132.04 (s; Ph); MS(EI): m/z (%): 816 ([M ] 100); IR: nÄ ˆ
total number of reflections measured was 6909 in the range 4.34 ꢁ
2q ꢁ 49.468, of which 6650 were unique. 5289 with F > 4s(F), 277
parameters. Final R indices: R1 ˆ 0.0530 (I > 2s(I)) and wR2 ˆ 0.1351
(all data). Residual electron density, max./min. 312/ À 326 enmÀ3. Th e
THF molecule was modeled as threefold disordered. Owing to this
disorder, the oxygen atom of THF could not be localized and was
modeled as a CH2 group. Crystallographic data (excluding structure
factors) for the structures reported in this paper have been deposited
with the Cambridge Crystallographic Data Centre as supplementary
publication nos. CCDC-143738 (2) and CCDC-143739 (3). Copies of
the data can be obtained free of charge on application to CCDC, 12
Union Road, Cambridge CB21EZ, UK (fax: (‡44)1223-336-033;
e-mail: deposit@ccdc.cam.ac.uk).
2143, 2129, 1596, 756, 691 cmÀ1; elemental analysis (C H N) is correct for
C54H58Al2N4.
ꢀ
3: HC CSiMe3 (2.0 mL, 14 mmol) was added in excess to a solution of 1
(0.83 g, 2.0 mmol) in toluene (50 mL). The mixture was stirred under reflux
for 1.5 hand then for 2 hat room temperature. The solvent was removed
and 3 was isolated in hexane as white crystals at À268C (1.0 g, 51%). Single
crystals suitable for X-ray diffraction analysis were obtained from THF at
À268C. M.p. 1338C. 1H NMR (200 MHz, C6D6): d ˆ 0.13 (s, 18H;
ꢀ
CSiMe3), 0.44 (s, 9H; SiMe3), 0.81 (s, 9H; C3-tBu), 1.56 (s, 9H; C1-tBu),
5.79 (s, 1H; C2-H), 7.42 (s, 1H; C44-H); 13C NMR (125 MHz, C6D6): d ˆ
À0.08 (s; Si1-Me3), 0.29 (s; Si2(3)-Me3), 32.91 (s; C10), 31.34 (s; C30), 30.79
ꢀ
(s; C31(32,33)), 29.52 (s; C11(12,13)), 103.80 (s; C44), 116.35 (s; Si2-C ),
[10] a) N. L. Narvor, L. Toupet, C. Lapinte, J. Am. Chem. Soc. 1995, 117,
7129; b) T. Yamagata, H. Imoto, T. Saito, Acta Crystallogr. Sect. C
1997, 53, 859; c) R. Beckhaus, M. Wagner, V. V. Burlakov, W.
Baumann, N. Peulecke, A. Spannenberg, R. Kempe, U. Rosenthal,
Z. Anorg. Allg. Chem. 1998, 624, 129.
[11] a) H. Suzuki, T. Murafuji, N. Azuma, J. Chem. Soc. Perkin Trans. 1
1992, 1593; b) L. Guo, J. D. Bradshaw, D. B. McConville, C. A. Tessier,
W. J. Young, Organometallics 1997, 16, 1685.
ꢀ
ˆ
125.40 (br; Al-C ), 141.80 (br; Al-C ), 134.62 (s; C2), 152.00 (s; C1), 163.08
(s; C3); 29Si NMR (99 MHz, C6D6): d ˆ À21.51 (s; Si2(3)), À5.74 (s; Si1);
IR: nÄ ˆ 3041, 2075, 1941, 1079, 955, 857, 618 cmÀ1; MS(EI): m/z(%): 498
‡
‡
([M ], 20), 441 ([M À AlMe2], 100); elemental analysis (C H N) is correct
for C26H47AlN2Si3.
Received: May 4, 2000 [Z15078]
[12] a) The idealized D2h symmetry consists of a planar six-membered
[1] a) G. Wilk, H. Müller, Justus Liebigs Ann. Chem. 1960, 629, 222;
b) J. J. Eisch, W. C. Kaska, J. Am. Chem. Soc. 1963, 85, 2165; c) P.
Binger, Angew. Chem. 1963, 75, 918; Angew. Chem. Int. Ed. Engl.
1963, 2, 686; d) R. Rienäcker, D. Schwengers, Liebigs Ann. Chem.
1970, 737, 182.
[2] a) D. Stucky, A. M. McPherson, W. E. Rhine, J. J. Eisch, J. L.
Considine, J. Am. Chem. Soc. 1974, 96, 1941; b) M. J. Albright,
W. M. Butler, T. J. Anderson, M. D. Glick, J. P. Oliver, J. Am. Chem.
Soc. 1976, 98, 3995.
À ꢀ
Al2N4 ring withlinear Al C C bonds making 908 dihedral angles with
the ring; b) I. B. Bersuker, V. Z. Polinger, Vibronic Interactions in
Molecules and Crystals, Springer, Berlin, 1989; c) L. F. Chibotaru, F.
Cimpoesu, Int. J. Quant. Chem. 1997, 65, 37. d) Calculations were
carried out with the GAMESS package in the RHF limit, with STO-
3G basis: M. W. Schmidt, K. K. Baldridge, J. A. Boatz, S. T. Elbert,
M. S. Gordon, J. H. Jensen, S. Koseki, N. Matsunaga, K. A. Nguyen, S.
Su, T. L. Windus, M. Dupuis, J. A. Montgomery, J. Comput. Chem.
1993, 14, 1347. e) We computed the vibronic curvature Kv(Au) ˆ
[3] a) G. Erker, M. Albrecht, C. Krüger, M. Nolte, S. Werner, Organo-
metallics 1991, 10, 3791; b) G. Erker, M. Albrecht, C. Krüger, M.
Nolte, S. Werner, Organometallics 1993, 12, 4979; c) M. Albrecht, G.
Erker, M. Nolte, C. Krüger, J. Organomet. Chem. 1992, 427, C21.
[4] B. M. Trost, M. R. Ghadiri, J. Am. Chem. Soc. 1986, 108, 1098, and
references therein.
À1
À0.2942 mdynŠ
‡0.2846 mdynŠ
,
while the nonvibronic curvature is K0(Au) ˆ
Thus, the total curvature is K0‡Kv ˆ
À1
.
À0.0096 mdynŠÀ1.f) The vibronically transformed orbitals were ob-
tained by a particular method. Technically, this resembles localization
procedures, but is related withthe vibronic terms.
[13] G. M. Sheldrick, SHELXL-97, Program for Crystal Structure Refine-
ment, University of Göttingen, Germany, 1997.
[5] a) Recently, pyrazolato ligands have attracted interest in transition
metal chemistry owing to their h2- and h5-coordination. See: J. R.
Perera, M. J. Heeg, H. B. Schlegel, C. H. Winter, J. Am. Chem. Soc.
1999, 121, 4536, and references therein; N. C. Mösch-Zanetti, R.
Â
Krätzner, C. Lehmann, T. R. Schneider, I. Uson, Eur. J. Inorg. Chem.
2000, 13; b) a homoleptic aluminum compound [Al(h2-tBu2pz)3] was
prepared: G. B. Deacon, E. E. Dilbridge, C. M. Forsyth, P. C. Junk,
B. W. Skelton, A. H. White, Aust. J. Chem. 1999, 52, 733; c) only a few
crystallographically characterized m-h1-h1-pyrazolate complexes of
aluminum are known: C.-C. Chang, T.-Y. Her, F.-Y. Hsieh, C.-Y. Yang,
M.-Y. Chiang, G.-H. Lee, Y. Wang, S.-M. Peng, J. Chin. Chem. Soc.
1994, 41, 783; M. H. Chisholm, N. W. Eilerts, J. C. Huffman, Inorg.
Chem. 1996, 35, 445; D. J. Darensbourg, E. L. Maynard, M. W.
Holtcamp, K. K. Klausmeyer, J. H. Reibenspies, Inorg. Chem. 1996,
35, 2682.
Ruthenium-Catalyzed Enyne Metathesis of
Acetylenic Boronates: A Concise Route for the
Construction of Cyclic 1,3-Dienylboronic Esters
Johanne Renaud,* Claus-Dieter Graf, and
Lukas Oberer
Â
[6] C. Fernandez-CastanÄo, C. Foces-Foces, N. Jagerovic, J. Elguero, J. Mol.
Struct. (THEOCHEM) 1995, 355, 265.
[7] R. A. Kovar, J. O. Callaway, C. H. van Dyke, N. D. Miro, Inorg. Synth.
1975, 17, 36.
[8] H. W. Roesky, W. Zheng, unpublished results.
Since its inception in the late 1980s, the ring-closing
metathesis (RCM) reaction of dienes has inspired a plethora
of exciting studies.[1] In comparison, the enyne ring-closing
metathesis reaction is less well documented. Most reports on
this topic are confined to the assembly of compounds
containing an unsubstituted or an alkyl-substituted 1,3-dienyl
[9] X-ray structure determination: The data were collected on a Stoe ±
Siemens ± Huber four-circle instrument (À1408C) for 2 and 3, with
graphite-monochromated MoKa radiation (l ˆ 0.71073 Š). The struc-
tures were solved by direct methods and refined against F 2 on all data
by full-matrix least-squares withSHELXS-97. [13] 2: C54H58Al2N4, Mr ˆ
817, monoclinic, space group C2/c, a ˆ 22.079(4), b ˆ 9.541(2), c ˆ
23.734(5) Š, b ˆ 96.60(3)8, Vˆ 4966.20(17) Š3, Z ˆ 4, 1calcd
ˆ
[*] Dr. J. Renaud, Dr. C.-D. Graf, L. Oberer[‡]
Novartis Pharma AG
1.093 MgmÀ3
,
crystal size: 0.6  0.4  0.2 mm3, F(000) ˆ 1744,
m(MoKa) ˆ 0.096 mmÀ1. The total number of reflections measured
was 3145 in the range 4.66 ꢁ 2q ꢁ 43.468, of which 2924 were unique,
2309 with F > 4s(F), 277 parameters. Final R indices: R1 ˆ 0.0487 (I >
2s(I)) and wR2 ˆ 0.1125 (all data). Residual electron density, max./
min. 253/ À 238 enmÀ3. 3: C26H47AlN2Si3 ´ C4H8O, Mr ˆ 571, monoclin-
ic, space group P21/n, a ˆ 12.261(3), b ˆ 16.424(3), c ˆ 20.151(4) Š,
K-136.3.25
4002 Basle (Switzerland)
Fax : (‡41)61-696-6071
E-mail: johanne.renaud@pharma.novartis.com
‡
[ ] NMR analyses.
b ˆ 103.02(3)8, Vˆ 3954(1) Š3, Z ˆ 4, 1calcd ˆ 0.959 MgmÀ3
, crystal
Supporting information for this article is available on the WWW under
http://www.wiley-vch.de/home/angewandte/ or from the author.
size: 0.5  0.5  0.15 mm3, F(000) ˆ 1248, m(MoKa) ˆ 0.163 mmÀ1. Th e
Angew. Chem. Int. Ed. 2000, 39, No. 17
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Table 1. Synthesis of 1,3-dialkenylboronates by enyne metathesis.[a]
Entry Enyne Product
Yield[b] Time Solvent[a]
motif.[2, 3] We recently demonstrated that cyclic alkenylbor-
onates can be obtained by RCM of dienylboronic esters.[4] In
connection with these studies, we considered the enyne ring-
closing metathesis reaction as a practical and concise strategy
for the construction of cyclic 1,3-dienylboronates [Eq. (1)]. In
[%]
[h]
1
87[c]
14
A
A
A
2
3
86[d, e]
1
5
93
addition to being amenable to further functionalization by
manipulation of the vinylboronate moiety,[5] 1,3-dialkenylbor-
onic esters are well poised to enter into Diels ± Alder cyclo-
addition reactions and therefore constitute highly versatile
synthetic intermediates. Here we disclose the first examples of
conversion of en-1-ynylboronic esters into five- to seven-
membered carbocyclic and heterocyclic 1,3-dialkenyl-2-boro-
nates by enyne metathesis. Additionally, we report that these
dienes readily undergo cycloaddition reactions withihgh
regio- and stereoselectivity.
Our synthetic route towards the preparation of the meta-
thesis substrates is summarized in Scheme 1. The critical
alkyn-1-ylboronate moiety was introduced by trapping an
alkynyllithium intermediate with a 2-alkoxy-4,4,5,5-tetra-
methyl-1,3,2-dioxaborolane (2 or 3) followed by treatment
with anhydrous ethereal HCl, according to a procedure
described by Brown et al.[6, 7]
4
94[d, f]
3
B
5
6
93
95
2
6
A
A
7
65[d, f]
12
B
8
9
81[d, f, g] 12
B
91
3
A
[a] Metathesis conditions: 5 ± 10 mol% catalyst 1, 0.06 m, RT. Solvent A:
CH2Cl2; solvent B: benzene. [b] Yields refer to isolated products. [c] Ethylene
atmosphere. [d] Overall yield from the alkynylboronate. [e] Diels ± Alder
ꢀ
conditions: MeO2CC CCO2Me, EtAlCl2, CH2Cl2, À78 to 08C, 2 h. [f] Diels ±
ꢀ
Alder conditions: MeO2CC CCO2Me or N-phenylmaleimide, benzene, 808C,
1 h. [g] Two diastereoisomers (drˆ 7:1). B(OR)2 ˆ B(OCMe2)2; Ts ˆ p-tol-
uenesulfonyl. Further details on the experimental procedure can be found in the
Supporting Information.
Scheme 1. Synthesis and enyne metathesis of en-1-ynylboronates. a) Pro-
cedure A: LDA, Et2O or THF, À788C, 5 ± 15 min; 2 or 3, 1 ± 3 h; HCl in
Et2O, À788C to RT; Procedure B: LDA was replaced by nBuLi.
ˆ
b) [(Cy3P)2Cl2Ru CHPh] (1, 5 ± 10 mol%), benzene or CH2Cl2, RT. Ts ˆ
Whilst five of the 1,3-dialkenylboronic esters synthesized
were isolated in good yield after chromatography (Table 1, 13,
15, 17, 18, and 21), the four containing unsubstituted five- or
seven-membered rings proved to be unstable upon concen-
tration, most likely because of dimerization.[10] To circumvent
this problem, these dienylboronic esters were directly trans-
formed into Diels ± Alder adducts (Scheme 2). Thus, reaction
of the intermediate 1,3-dialkenylboronates with N-phenyl-
maleimide or withdimetyhl acetylenedicarboxylate under
thermal or Lewis acid catalyzed conditions[11] led cleanly to
the expected cycloaddition products (Table 1, entries 2, 4, 7,
and 8). The tandem enyne metathesis/Diels ± Alder cyclo-
p-toluenesulfonyl; LDA ˆ lithium diisopropylamide.
With the alkynylboronic esters in hand, we next established
the experimental conditions for the ring-closing enyne meta-
thesis (Scheme 1). The reactions were routinely carried out in
the presence of 5 ± 10 mol% of Grubbsꢁ catalyst (1)[8] in
CH2Cl2 at room temperature.[9] As shown in Table 1, the
ruthenium-promoted enyne metathesis efficiently converts a
range of substrates into five- and six-membered carbocyclic
and heterocyclic 1,3-dienylboronates. The yields are excellent,
ranging from 87 to 95%, and the reactions are generally
complete within 1 ± 14 h (Table 1, entries 1, 3, 5, 6, and 9).
3102
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one predominant isomer (Scheme 4). A minor component of
the mixture was shown to be the b-epimer of 25.[14] By analogy
with the results obtained in the cycloaddition reaction with
nitroethylene, the other minor product was assigned the
structure corresponding to the endo regioisomer. In the
reaction of 21 withmetyhl vinyl ketone, by-product
26
resulting from dimerization of 21 was isolated in 9% yield.[12]
To broaden the utility of our synthetic route to cyclic 1,3-
dienyl-2-boronic esters, we tackled the conversion of higher
molecular weight alkynylboronic esters into their cyclic
counterparts, with the aim of circumventing the purification
step. We examined the transformation of dienyne 27 into the
bicyclic vinylboronate 29 (Scheme 5). We were gratified to
find that the crude alkynylboronate 28 cleanly underwent
Scheme 2. Diels ± Alder cycloaddition reaction of 1,3-dialkenylboronates.
ꢀ
ꢀ
a) MeO2CC CCO2Me, EtAlCl2, CH2Cl2, À78 to 08C, 2 hor MeO 2CC C-
CO2Me, benzene, 808C, 1 h. b) N-Phenylmaleimide, benzene, 808C, 1 h.
addition sequence was accomplished efficiently without
removal of the ruthenium catalyst in yields of 65 to 94%.
Although 16 resulted from the exclusive endo addition of the
dienophile, adduct 20 was obtained as a 7:1 mixture of the
endo:exo isomers.[12]
The ability of cyclic 1,3-dialkenylboronic esters to undergo
Diels ± Alder reactions in a regio-[13] and stereoselective
fashion was substantiated by examining the cycloaddition
reactions of dialkenylboronate 21 (Schemes 3 and 4). Treat-
ment of 21 withan excess of nitroethylene at 40 8C for 2 h
furnished one major product (22) in 89% yield, along witha
Scheme 5. Synthesis of bicyclic dienylboronate 29. a) LDA, THF, À788C,
20 min; 2-ethoxy-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (2), 2 h; HCl in
Et2O, À788C to RT; removal of solvents and filtration. b) [(Cy3P)2-
ˆ
Cl2Ru CHPh] (1, 5 mol%), CH2Cl2, RT, 3 h , 70%.
ruthenium-promoted metathesis in 70% yield.[15] The resul-
tant bicyclic dialkenylboronic ester 29 was efficiently oxidized
to the corresponding enone 31 by treatment withanhydrous
Me3NO in refluxing THF (Scheme 6). Alternatively, reaction
of 29 with3-bromobenzonitrile in the presence of CsF and a
catalytic amount of [PdCl2(dppf)] ´ CH2Cl2 in refluxing DME
furnished the cross-coupling product 30.
Scheme 3. Selectivity of the Diels ± Alder reaction with nitroethylene.
a) CH2CHNO2 (10 equiv), benzene, 408C, 2 h. b) NaOMe (1.2 equiv),
THF:MeOH (3:1), RT, 2 h, 73%.
Scheme 6. Conversion of dienylboronate 29 to 30 and 31. a) 3-Bromoben-
zonitrile, CsF, [PdCl2(dppf)] ´ CH2Cl2, DME, reflux, 14 h, 88%. b) Me3NO
(anhydrous), THF, 708C, 1.5 h, 76%. dppf ˆ 1,1'-bis(diphenylphosphanyl)-
ferrocene.
Scheme 4. Selectivity of the Diels ± Alder cycloaddition reaction. a) For
R1 ˆ CHO: CH2CHCHO (10 equiv), benzene, 658C, 3 h. For R1 ˆ COCH3:
CH2CHCOCH3 (10 equiv), benzene, 708C, 4 h.
In summary, we have developed an unprecedented enyne
metathesis-based approach for the concise construction of
cyclic 1,3-dialkenylboronates. We have further demonstrated
that these 1,3-dialkenylboronic esters undergo Diels ± Alder
reactions withelectron-deficient dienophiles withexcellent
regio- and stereoselectivity to give vinylboronates of higher
molecular complexity in a short sequence of steps. Further
investigations to broaden the scope of this enyne metathesis
and to explore asymmetric Diels ± Alder cycloadditions by
using chiral, enantiomerically pure 1,3-dienyl-2-boronates are
in progress.
mixture of isomers 23 and 24 (1:1.8; 8% yield), which
accounted for most of the remaining material (Scheme 3).
The identity of the major compound 22 was ascertained by
X-ray crystallography, and the structures of 23 and 24 were
assigned on the basis of NMR experiments.[12] The structure of
23 was also confirmed independently by epimerization of 22
under basic conditions.[14]
Likewise, the reaction of 21 withacrolein or methyl vinyl
ketone was highly regio- and stereoselective and produced
Received: March29, 2000 [Z14917]
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[1] Recent reviews on metathesis: a) A. Fürstner, Top. Organomet. Chem.
1998, 1, 1 ± 231; b) R. H. Grubbs, S. Chang, Tetrahedron 1998, 54,
4413 ± 4450; c) S. K. Armstrong, J. Chem. Soc. Perkin Trans. 1 1998,
371 ± 388; d) M. Schuster, S. Blechert, Angew. Chem. 1997, 109, 2124 ±
2145; Angew. Chem. Int. Ed. Engl. 1997, 36, 2036 ± 2056.
[2] The two reported examples of enyne metathesis of acetylenes bearing
silyl substituents provide the corresponding dienes in 20 and 7% yield,
respectively: a) J. S. Clark, G. P. Trevitt, D. Boyall, B. Stammen, Chem.
Commun. 1998, 2629 ± 2630; b) reference [31].
[3] For recent studies on intramolecular enyne and dienyne metathesis,
see: a) M. Mori, T. Kitamura, N. Sakakibara, Y. Sato, Org. Lett. 2000,
2, 543 ± 545; b) T. R. Hoye, S. M. Donaldson, T. J. Vos, Org. Lett. 1999,
1, 277 ± 279; c) M. A. Leeuwenburgh, C. Kulker, H. I. Duynstee, H. S.
Overkleeft, G. A. van der Marel, J. H. van Boom, Tetrahedron 1999,
55, 8253 ± 8262; d) A. G. M. Barrett, S. P. D. Baugh, D. C. Braddock,
K. Flack, V. C. Gibson, M. R. Giles, E. L. Marshall, P. A. Procopiou,
A. J. P. White, D. J. Williams, J. Org. Chem. 1998, 63, 7893 ± 7907; e) M.
Mori, N. Sakakibara, A. Kinoshita, J. Org. Chem. 1998, 63, 6082 ±
6083; f) M. Picquet, C. Bruneau, P. H. Dixneuf, Chem. Commun. 1998,
2249 ± 2250; g) D. A. Heerding, D. T. Takata, C. Kwon, W. F. Huffman,
J. Samanen, Tetrahedron Lett. 1998, 39, 6815 ± 6818; h) S. Kotha, N.
Sreenivasachary, E. Brahmachary, Tetrahedron Lett. 1998, 39, 2805 ±
2808; i) K. Hammer, K. Undheim, Tetrahedron 1997, 53, 10603 ±
10614; j) A. Kinoshita, M. Mori, Heterocycles 1997, 46, 287 ± 299;
k) S.-H. Kim, W. J. Zuercher, N. B. Bowden, R. H. Grubbs, J. Org.
Chem. 1996, 61, 1073 ± 1081; l) A. Kinoshita, M. Mori, Synlett 1994,
1020 ± 1022; m) N. Chatani, T. Morimoto, T. Muto, S. Murai, J. Am.
Chem. Soc. 1994, 116, 6049 ± 6050.
A Light-Modulated Sequence-Specific
DNA-Binding Peptide**
Â
Â
Ä
Ä
Ana M. Caamano, M. Eugenio Vazquez, Jose Martínez-
Â
Costas, Luis Castedo, and Jose L. Mascarenas*
In eukaryotes, gene expression is primarily regulated at the
transcription level through the action of a host of sequence-
specific DNA-binding proteins known as transcription fac-
tors.[1] At any given time, most transcription factors are
present in the cell in an inactive form and they become
activated upon sensing and responding to specific external
signals.[2] In a number of cases, it has been shown that
activation involves the transcription factor undergoing a
stimulus-induced conformational change that converts it from
a non DNA binding protein into a form capable of recognizing
the appropriate binding site at the promotor.[3] We reasoned
that molecules mimicking this natural activation mechanism,
which are capable of binding to specific DNA sequences with
high affinity only after receiving an external stimulus, might
offer a promising potential for applications in cell biology and
molecular medicine[4] and could provide new insights into the
mechanisms underlying DNA recognition. As a first step
towards this goal, we have designed a peptide whose
sequence-specific DNA-binding affinity can be modulated
by light.[5]
Our design is inspired by the well-known ability of
artificially dimerized basic regions (BRs) of bZIP proteins
to recognize DNA sites.[6, 7] We envisaged that appropriate
linking of these BRs through a rigid photoresponsive device
suchas an azobenzene moiety, capable of undergoing a
substantial geometrical change upon irradiation,[8] might
allow modulation of the site-specific DNA affinity of the
resulting dimer. In designing the system we sought to favor
the DNA-binding ability of the cis over the trans isomer by
taking advantage of the considerably shorter distance be-
tween the benzylic carbon atoms of the cis-azobenzene
template and the favorable preorientation of its recognition
arms to grip the major groove of the DNA (Scheme 1).
Molecular modeling corroborated this idea for hybrid 3
(Scheme 2); each of the peptide segments of 3 consists of
amino acids 226 ± 248 from the BR of the yeast transcription
[4] J. Renaud, S. G. Ouellet, J. Am. Chem. Soc. 1998, 120, 7995 ± 7996.
[5] a) Pd-catalyzed cross-coupling reactions: N. Miyaura, A. Suzuki,
Chem. Rev. 1995, 95, 2457 ± 2483; b) addition to iminium ions: R. A.
Batey, D. B. MacKay, V. Santhakumar, J. Am. Chem. Soc. 1999, 121,
5075 ± 5076; c) oxidation to ketones: G. Desurmont, S. Dalton, D. M.
Giolando, M. Srebnik, J. Org. Chem. 1996, 61, 7943 ± 7946.
[6] H. C. Brown, N. G. Bhat, M. Srebnik, Tetrahedron Lett. 1988, 29,
2631 ± 2634.
[7] The alkynylboronic esters are susceptible to hydrolysis and were
therefore most conveniently isolated by distillation of the crude
reaction mixture.
ˆ
[8] [(Cy3P)2Cl2Ru CHPh] (1): a) P. Schwab, R. H. Grubbs, J. W. Ziller, J.
Am. Chem. Soc. 1996, 118, 100 ± 110; b) P. Schwab, M. B. France, J. W.
Ziller, R. H. Grubbs, Angew. Chem. 1995, 107, 2179 ± 2181; Angew.
Chem. Int. Ed. Engl. 1995, 34, 2039 ± 2041.
[9] Two independent experiments were generally performed, one of
which was conducted in an NMR tube to monitor the reaction time.
[10] a) The facile dimerization reaction of a 1,3-butadien-2-ylboronic ester
has been reported: A. Kamabuchi, N. Miyaura, A. Suzuki, Tetrahe-
dron Lett. 1993, 34, 4827 ± 4828; b) for the dimerization of other 1,3-
dienes, see reference [3b], and references therein.
[11] P.-Y. Renard, Y. Six, J.-Y. Lallemand, Tetrahedron Lett. 1997, 38,
6589 ± 6590.
[12] The structural assignments were based on the data obtained from
1H NMR spectra (coupling constants) and in addition on COSY,
HSQC, and ROESY experiments.
[13] The cycloaddition reaction of 1,3-butadien-2-ylboronic ester with
acrolein and methyl vinyl ketone was shown to yield regioselectively
the 1,4-disubstituted products; see reference [10a].
[14] Epimerization of the Diels ± Alder adducts with NaOMe (1.2 equiv) in
THF:MeOH (3:1) at room temperature afforded quantitatively the b
epimers; this allowed identification of one of the minor isomers.
[15] The LiCl or iPr2NH2Cl resulting from the preparation of the
intermediate alkynylboronate 28 was removed by filtration through
Whatman glass fiber filters before the metathesis reaction.
Ä
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[*] Prof. Dr. J. L. Mascarenas, A. M. Caamano, M. E. Vazquez,
Prof. Dr. L. Castedo
Â
Departamento de Química Organica y Unidad Asociada al CSIC
Universidad de Santiago de Compostela
15706 Santiago de Compostela (Spain)
Fax : (‡34)981-595-012
E-mail: qojoselm@usc.es
Dr. J. Martínez-Costas
Departamento de Bioquímica y Biología Molecular
Universidad de Santiago de Compostela
15706 Santiago de Compostela (Spain)
[**] This work was supported by the Spanish M.E.C. (PB97 ± 0524) and the
Xunta de Galicia (XUGA 20906B96). A.M.C and E.V. thank the
Xunta de Galicia and the University of Santiago for their predoctoral
fellowships. We are grateful to Prof. M. Mosquera and Prof. J.
Benavente for allowing us to use the spectrofluorimetry and radio-
activity facilities, respectively, and to Dr. Chris Abell (Cambridge
University, Iberdrola Visiting Professor at the University of Santiago)
for critical reading of the manuscript.
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