Enyne metathesis on prop-2-ynyl-2,3-dideoxy-α-D-erythro-hex-2-enopyranosides

Article abstract of DOI:10.1055/s-2001-13352

The enyne metathesis on differently functionalized prop-2-ynyl-2,3-dideoxy-α-D-erythro-hex-2-enopyranosides (1, 2 and 3) has been analyzed for the first time, and the new and interesting results are described here.

Full text of DOI:10.1055/s-2001-13352

652
LETTER
Enyne Metathesis on Prop-2-ynyl-2,3-dideoxy- -D-erythro-hex-2-
enopyranosides
José Marco-Contelles,* Nieves Arroyo, Juliana Ruiz-Caro
Laboratorio de Radicales Libres (IQOG, CSIC), C/Juan de la Cierva, 3; 28006-Madrid, Spain
Fax 34 91 564 48 53; E-mail: iqoc21@iqog.csic.es
Received 9 March 2001
"endo-Oxygen"
"exo-Oxygen"
Abstract: The enyne metathesis on differently functionalized prop-
2-ynyl-2,3-dideoxy- -D-erythro-hex-2-enopyranosides (1, 2 and 3)
has been analyzed for the first time, and the new and interesting re-
sults are described here.
XO
XO
AcO
AcO
O
C-1
O
a or b
O
OX
C-α
C-β
4 X= H
Key words: enyne, metathesis, prop-2-ynyl-2,3-dideoxy- -D-
erythro-hex-2-enopyranosides, Grubbs’ catalyst, -furans
c
5 X= Ac
1 X= Bn
2 X= Ac
Scheme 2 Metathesis of enyne 2.
Reagents: a) Grubbs’catalyst, CH2Cl2 (8%), b) PtCl2, toluene (19%);
c: Ac2O, py, rt (50%)
The ring closing metathesis (RCM) reaction is one of the
most useful and efficient methods for ring annulation in
synthetic organic chemistry.1 In particular, the intramo-
lecular enyne metathesis2 has provided a series of recent
examples which show the success of this technology for
the synthesis of complex carbo- or heterocyclic ring sys-
tems via different types of catalytic systems.3 As shown in
Scheme 1 the intramolecular enyne metathesis on sub-
strates of type A affords bridged bicyclic derivatives (B)
in good yield, in one single synthetic operation.3 The
mechanism of this skeletal rearrangement is a matter of
debate. For the common metathesis using alkylidene com-
plexes of ruthenium, a metalocyclobutene intermediate
has been proposed.1 For the reactions involving Pd or Pt
complexes a formal [2+2] cycloaddition to a cyclobutene
followed by a [2+2] cycloreversion3 has been advanced.
More recently, a new mechanism has been considered
based on a “nonclassical” homoallyl-cyclopropylmethyl-
cyclobutyl cation as a key intermediate.4
which under the standard metathesis conditions, using
PtCl2 or Grubbs’ catalyst, gave a complex reaction mix-
ture which was not investigated further. Next the readily
available product 210 was submitted to the standard met-
athesis conditions, using PtCl2 or Grubbs’ catalyst, to give
product 4 in 19% (34%)12 and 8% (19%)12 yields, respec-
tively (Scheme 2). This product showed no signals in the
1H NMR spectrum corresponding to the O-propargyl moi-
ety, but data [(300 MHz, CDCl3) 5.97-5.86 (m, 2 H, H-
2, H-3), 5.48 (br s, 1 H, H-1), 5.32 (br d, J4,5 = 8.8 Hz, 1
H, H-4), 4.34-4.20 (m, 3 H, H-5, 2 H-6), 2.95 (br s, 1 H,
OH), 2.12, 2.11 (2 s, 2 OCOCH3)] was in good agree-
ment with those described for 4,6-di-O-acetyl-2,3-
dideoxy- -D-erythro-hex-2-enopyranose,13
indicating
that compound 4 is presumably a mixture of the (major)
and (minor) anomers, as other minor signals were ob-
served in this spectrum. After acetylation, lactol 4 gave
acetate 514 in 50% yield as a mixture of - and -anomers
in a 3 to 1 ratio, respectively (Scheme 2). With these re-
sults, we next investigated precursor 3.11 Using PtCl2 as
catalyst we could only isolate the known methyl 4,6-O-
benzylidene-2,3-dideoxy- -D-erythro-hex-2-enopyrano-
side (6)15 in 13% yield (14%)12 (Scheme 3). The use of
Grubbs’ catalyst again afforded product 6 [21% yield
(28%)12] along with two more products, 7 [8% yield
(11%)12] and 8 [10% yield (13%)12].16 The structure of
these compounds was established by their analytical,
spectroscopic data and by analysis of the corresponding
acetylated derivatives 9 and 10.16 Note that in these com-
pounds the stereochemistry at the double bond follows
from the vicinal coupling constant for the olefinic signals
[J(H-4/H-5): 15.8 Hz in E-9, and 11.5 Hz in Z-10]; the
A
B
Scheme 1 Intramolecular metathesis of enynes
In our current interest in the metal catalyzed cycloisomer-
ization on enynes installed in sugar templates (Pauson-
Khand reaction)5 and in the RCM of acyclic dienes de-
rived from carbohydrates,6,7 we have directed our atten-
tion to the metathesis of enynes derived from sugars. Only
some isolated examples in this subject have been reported
in the literature.8
Thus with these precedents in mind we have started our
project and prepared some prop-2-ynyl-2,3-dideoxy- -D-
erythro-hex-2-enopyranosides (1,9 210 and 311), isolated as
pure -anomers at C-1. First of all we have tested sugar 1,9
1
-substituted furan ring showed typical signals in the H
NMR spectrum [( ) (9: 7.43, s, 1 H, H- ’; 7.39, m, 1 H,
H- ; 6.56, s, 1 H, H- ; 10: 7.58, s, 1 H, H- ’; 7.45, t,
Synlett 2001, No. 5, 652–654 ISSN 0936-5214 © Thieme Stuttgart · New York

LETTER
Enyne Metathesis on Prop-2-ynyl-2,3-dideoxy- -D-erythro-hex-2-enopyranosides
653
Ph
H
O
O
O
b
O
O
OCH3
Ph
H
O
H
H
Ph
H
O
O
Ph
H
O
6 (13%)
6 (21%)
O
O
OX
a
OX
O
+
+
3
8 X= H (10%)
H1
H
7 X= H (8%)
O
H3
c
H1'
OAc
c
O
10 X= Ac (88%)
O
9 X= Ac (60%)
4
5
H2
β'
β
α'
O
α
9
Scheme 3 Metathesis of enyne 3
Reagents: a) Grubbs’catalyst, CH2Cl2; b) PtCl2, toluene;c: Ac2O, py, rt.
O
O
Ph
H
O
O
O
O
Ph
H
Ph
H
O
O
O
O
O
O
6
3
Ru
Ru
Ru
R
R
R
C
H
H
H
O
O
Ph
H
O
H
Ph
H
O
O
O
O
Ph
H
O
O
O
7 + 8
O
Ru
H
H
R
Ru
R
O
H
D
Scheme 4 Mechanism for the enyne metathesis of precursor 3.
J = 1.6 Hz, 1 H, H- ; 6.54, s, 1 H, H- )] and in the 13C quential aromatization. The exact mechanism for these
NMR spectra [( ) (9: 143.3, d, C- ’; 141.9, d, C- ; 123.6, processes as well as the hydrogenolysis (possibly in inter-
q, C- ’; 107.8, d, C- ; 10: 143.3, d, C- ’; 141.8, d, C- ; mediate C) leading to major compound 6, still remain to
121.4, q, C- ’; 111.1, d, C- )]; the rest of the functional be elucidated.
and structural moieties on molecules 9 and 10 correspond-
ed to the “sugar C-6/C-4 part” present in precursor 3.
In summary, the first analysis of the enyne metathesis on
prop-2-ynyl- -D-erythro-hex-2-enopyranosides has been
The formation of compounds 7 and 8, which only occurs reported. We have found that the reaction is substrate de-
from precursor 3 and in the metathesis reaction catalyzed pendent and that the major reaction path is the hydro-
by Grubbs’ complex, was totally unexpected, but it can be genolysis of the O-endo-C1 bond (precursor 2) or the
rationalized as shown in Scheme 4, according to the cleavage of the O-exo-C -C( )acetylene bond (precursor
mechanism proposed by Mori.3 The formation of the met- 3) (Scheme 2). In substrate 3 we have also found other
allocyclobutene C gives a carbene which after two se- products from the “normal” enyne metathesis product -a
quential intramolecular metathesis reactions affords the very unstable 1,4-dihydrofuran ring system, was not de-
expected diene D having a necessarily cis stereochemistry tected- which after hydrogenolysis and aromatization
at the double bond. However, this intermediate was not should afford the open-chain -substituted furans. Work
detected; presumably it must be very unstable and should is now in progress to explore the scope and limitations of
be transformed into the -substituted furans 7 and 8 by O/ this reaction and to determine the mechanism of these
C-1 bond cleavage, double bond isomerization and se- transformations.
Synlett 2001, No. 5, 652–654 ISSN 0936-5214 © Thieme Stuttgart · New York

654
J. Marco-Contelles et al.
LETTER
6.16 (br dd, J2,3 = 10 Hz, J = 4.4 Hz, 1 H, H-3), 5.90 (br d,
2,3 = 10 Hz, 1 H, H-2), 5.16 (m, 1 H, H-4), 4.29-4.19 (m, 2 H,
2 H-6), 4.17-4.06 (m, 1 H, H-5), 2.12, 2.10 (2 s, 9 H,
OCOCH3).
References and Notes
J
(1) Reviews: Grubbs, R. H.; Chang, S. Tetrahedron 1998, 54,
4413; Armstrong, S. K. J. Chem. Soc., Perkin Trans. 1 1998,
371; Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl.
1997, 36, 2036; Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc.
Chem. Res. 1995, 28, 446; Schmalz, H.-G. Angew. Chem., Int.
Ed. Engl. 1995, 34, 1833; Fürstner, A.; Langemann, Synthesis
1997, 793; Fürstner, A. Top. Catal. 1997, 4,285; Schuster, M.;
Blechert, S. Angew. Chem. 1997, 36, 2124; Fürstner, A.
Angew. Chem. Int. Ed. 2000, 39, 3012.
3
(15) Yamazaki, T.; Matsuda, K.; Sugiyama, H.; Seto, S.; Yamaoka,
N. J. Chem. Soc., Perkin Trans. 1 1977, 1981.
(16) In a typical experiment, product (3) (103 mg, 0.38 mmol) was
dissolved in dry CH2Cl2 (19 mL) and after bubbling argon into
the solution for 10 min, benzylidenebis(tricyclohexyl-
phosphine)-dichlororuthenium (31.3 mg, 0.038 mmol, 10
mol%) was added under argon and at r.t. This suspension was
stirred for 24 h; then a new and similar quantity of the catalyst
was added. After a further 24 h, the mixture was evaporated
and the residue submitted to chromatography (hexane/ethyl
acetate, on silica gel, from 4% to 10%) giving recovered 3 (25
mg), 615 [20 mg, 21% yield (28%)12], 7 [8 mg, 8% yield
(11%)12] and 8 [10 mg, 10% yield (13%)12]. Compounds 7 and
8 were submitted to acetylation, under standard conditions, to
(2) For the pioneer work in this subject, see: Katz, T. J.; Sivavec,
T. M. J. Am. Chem. Soc. 1985, 107, 737.
(3) Grubbs’ catalyst: Kinoshita, A.; Mori, M. Synlett 1994,
1020; Kinoshita, A.; Mori, M. J. Org. Chem. 1996, 61, 8356.
[RuCl2(CO)3]2: Chatani, N., Morimoto, T.; Muto, T.; Murai,
S. J. Am. Chem. Soc. 1994, 116, 6049. PtCl2: Trost, B. M.;
Doherty, G. A. J. Am. Chem. Soc. 2000, 122, 3802; Fürstner,
A.; Szillat, H., Gabor, B.; Mynott, R. J. Am. Chem. Soc. 1998,
120, 8305. TCPC (2,3,4,5-tetrakis(methoxy-
carbonyl)palladacyclopentadiene): Trost, B. M.; Trost,
M. K. J. Am. Chem. Soc. 1991, 113, 1850.
(4) Fürstner, A.; Szillat, H., Stelzer, F. J. Am. Chem. Soc. 2000,
122, 6785.
(5) Marco-Contelles, J. Tetrahedron Lett. 1994, 35, 5059; Marco-
Contelles, J. J. Org. Chem. 1996, 61, 7666; Marco-Contelles,
J.; Ruiz, J. Tetrahedron Lett. 1998, 39, 6393; Marco-
Contelles, J.; Ruiz, J. J. Chem Res. (S) 1999, 160.
(6) For a review, see: Roy, R., Das, K. Chem. Commun. 2000, 51.
(7) Marco-Contelles, J.; de Opazo, E. J. Org. Chem. 2000, 65,
5416; Marco-Contelles, J.; de Opazo, E. Tetrahedron Lett.
2000, 41, 2439.
(8) Leeuwenburgh, M. A.; Kulker, C., Duynstee, H.; Overkleft,
H. S., van der Marel, G. A.;van Boom, J. H. Tetrahedron
1999, 55, 8253; Clark, J. S.; Hamelin, O. Angew. Chem. Int.
Ed. 2000, 39, 372.
(9) Marco-Contelles, J.; Ruiz-Caro, J. J. Org. Chem. 1999, 64,
8302.
(10) Ferrier, R. J. J. Chem. Soc., Perkin Trans. 1 1964, 5443.
(11) Marco-Contelles, J.; Ruiz-Caro, J.Tetrahedron Lett. 2001, 42,
1515.
25
yield acetates 9 and 10, respectively. 9: mp 121-124 ºC; [ ]D
-33 (c 0.4, CHCl3); IR (KBr) 2927, 1742, 1461, 1378, 1241,
1053 cm-1; 1H NMR (300 MHz, CDCl3) 7.54-7.51 [m, 2 H,
O(CHC6H5)O], 7.43 (m, 1 H, H- ’), 7.39-7.26 [m, 4 H, H- ,
O(CHC6H5)O], 6.60 (d, J4,5 = 15.8 Hz, 1 H, H-5), 6.56 (m, 1
H, H- ), 5.96 (dd, J4,5 = 15.8 Hz, J3,4 = 7.1 Hz, 1 H, H-4), 5.62
[s, 1 H, O(CHC6H5)O], 4.94 (dt, J1ax,2 = J2,3 = 10.5 Hz,
J
J
1eq,2’ = 5.2 Hz, 1 H, H-2), 4.45 (dd, J1ax,1eq = 10.5 Hz,
1eq,2 = 5.2 Hz, 1 H, H-1eq), 4.35 (dd, J3,4 = 7.1 Hz, J2,3 = 10.5
Hz, 1 H, H-3), 3.72 (t, J1ax,1eq = J1ax,2 = 10.5 Hz, 1 H, H-1ax),
2.07 (s, 3 H, OCOCH3); 13C NMR (75 MHz, CDCl3) 169.9
(OCOCH3), 143.8 (C- ), 141.3 (C- ’), 137.4 (q), 129.4 (d),
128.5 (2 C), 126.4 (2 C) [O(CHC6H5)O], 124.7 (C-4), 124.2
(C-5), 123.6 (C- ’), 107.8 (C- ), 101.6 [O(CHC6H5)O], 80.6
25
(C-3), 68.4 (C-1), 66.6 (C-2), 21.1 (OCOCH3). 10: oil; [ ]D
-40 (c 0.4, CHCl3); IR (KBr) 2927, 1743, 1656, 1455, 1378,
1229 cm-1; 1H NMR (300 MHz, CDCl3) 7.58 (m, 1 H, H- ’),
7.54-7.47 [m, 2 H, O(CHC6H5)O], 7.45 (t, J = 1.6 Hz, 1 H, H-
), 7.40-7.35 [m, 3 H, O(CHC6H5)O], 6.54 (d, J = 1.6 Hz, 1 H,
H- ), 6.51 (d, J4,5 = 11.5 Hz, 1 H, H-5), 5.65 (dd, J4,5 = 11.5
Hz, J3,4 = 8.7 Hz, 1 H, H-4), 5.62 [s, 1 H, O(CHC6H5)O], 5.06
(dt, J1ax,2 = J2,3 = 10.3 Hz, J1eq,2’ = 5.2 Hz, 1 H, H-2), 4.74 (dd,
J
3,4 = 8.7 Hz, J2,3 = 10.4 Hz, 1 H, H-3), 4.44 (dd, J1ax,1eq = 10.4
(12) Taking into account the recovered starting material.
(13) Baer, H. H.; Siemsen, L.; Defaye, J.; Burak, K. Carbohydr.
Res. 1984, 134, 49; Moufid, N.; Chapleur, Y.; Mayon, P. J.
Chem. Soc., Perkin Trans. 1 1992, 991.
(14) Madaj, J.; Rak, J.; Sokolowski, J.; Wisniewski, A. J. Org.
Chem. 1996, 61, 2988. In contrast to what is described in this
paper, we analyzed compound 5 (major isomer) as follows:
1H NMR (300 MHz, CDCl3) 6.31 (br s, 1 H, H-1), 6.03 (d,
Hz, J1eq,2’ = 5.2 Hz, 1 H, H-1eq), 3.77 (t, J1ax,1eq = J1ax,2 = 10.3
Hz, 1 H, H-1ax), 2.00 (s, 3 H, OCOCH3); 13C NMR (75 MHz,
CDCl3) 169.7 (OCOCH3), 143.3 (C- ), 141.8 (C- ’), 137.2
(q), 129.2 (d), 128.4 (2 C), 126.2 (2 C) [O(CHC6H5)O], 126.6
(C-4), 125.1 (C-5), 121.4 (C- ’), 111.1 (C- ), 101.2
[O(CHC6H5)O], 76.0 (C-3), 68.3 (C-1), 66.5 (C-2), 20.8
(OCOCH3).
J
2,3 = 10 Hz, 1 H, H-3), 5.86 (dt, J2,3 = 10 Hz, J = 2.8 Hz, 1 H,
H-2), 5.38 (dq, J4,5 = 10.4 Hz, J = 1.6 Hz, 1 H, H-4), 4.29-4.19
(m, 2 H, 2 H-6), 4.17-4.06 (m, 1 H, H-5), 2.12, 2.10 (2 s, 9 H,
Article Identifier:
1437-2096,E;2001,0,05,0652,0654,ftx,en;D01001ST.pdf
3
OCOCH3), and for compound 5 (minor isomer) as
follows: 1H NMR (300 MHz, CDCl3) 6.35 (br s, 1 H, H-1),
Synlett 2001, No. 5, 652–654 ISSN 0936-5214 © Thieme Stuttgart · New York