Ruthenium-catalyzed olefin metathesis double-bond isomerization sequence

Article abstract of DOI:10.1021/jo048937w

A novel ruthenium-catalyzed tandem ring-closing metathesis (RCM) double-bond isomerization reaction is described in this paper. The utility of this method for the efficient syntheses of five-, six-, and seven-membered cyclic enol ethers is demonstrated. It relies on the conversion of a metathesis-active ruthenium carbene species to an isomerization-active ruthenium-hydride species in situ. This conversion is achieved by using various additives. Scope and limitations of the different protocols are discussed, and some mechanistic considerations based on ³¹P and ¹H NMR spectroscopic studies are presented.

Full text of DOI:10.1021/jo048937w

Ru th en iu m -Ca ta lyzed Olefin Meta th esis Dou ble-Bon d
Isom er iza tion Sequ en ce
Bernd Schmidt
FB Chemie-Organische Chemie I, Universita¨t Dortmund, Otto-Hahn-Strasse 6,
D-44227 Dortmund, Germany
bschmidt@chemie.uni-dortmund.de
Received J une 23, 2004
A novel ruthenium-catalyzed tandem ring-closing metathesis (RCM) double-bond isomerization
reaction is described in this paper. The utility of this method for the efficient syntheses of five-,
six-, and seven-membered cyclic enol ethers is demonstrated. It relies on the conversion of a
metathesis-active ruthenium carbene species to an isomerization-active ruthenium-hydride species
in situ. This conversion is achieved by using various additives. Scope and limitations of the different
protocols are discussed, and some mechanistic considerations based on 31P and 1H NMR spectroscopic
studies are presented.
In tr od u ction
most cases, the more active but less conveniently avail-
able molybdenum or second-generation ruthenium cata-
lysts are required. Furthermore, efficient ring-closing
metathesis (RCM) of enol ethers makes high dilution
necessary; otherwise, dimerization of the metathesis
precursors might compete. In some cases, these draw-
backs have been circumvented by the ring-closing me-
tathesis of allyl ethers,21 which is normally an extraor-
dinarily facile process, followed by a base-mediated22 or
transition-metal-catalyzed isomerization23-25 of the pri-
mary RCM products. The disadvantage of the latter
strategy is obviously the additional synthetic step, which
often requires the use of expensive or less conveniently
available catalysts (Scheme 1).
Over the decade that has passed since stable and
defined carbene complexes of molybdenum1 and ruthe-
nium2 were introduced as efficient precatalysts for olefin
metathesis,3-6 this synthetic method has become a valu-
able tool, especially for the synthesis of heterocycles.7,8
From the synthetic point of view, cyclic enol ethers are
particularly important heterocycles as they have wide-
spread use in carbohydrate chemistry9-11 and can be used
as precursors for R,R′-disubstituted oxacyclic frame-
works12 and as masks for functionalized aldehydes.13
Although significant progress has been made in enol
ether metathesis over the past few years,14-20 the reaction
still appears to have some drawbacks. For instance, in
We became involved in the problem of the olefin
metathesis-based synthesis of cyclic enol ethers in the
course of a program directed at the synthesis of cyclic
diarylheptanoids. These natural products are isolated
from the plant Alpinia blepharocalyx and show ac-
tivity against human HT-1080 fibrosarcoma and murine
colon 26-L5 carcinoma cells.26 The simplest example is
(3S,7R)-5,6-dihydro-1,7-bis(4-hydroxyphenyl)de-O-meth-
ylcentrolobine (A).27 We envisaged a synthetic strategy
(1) Schrock, R. R.; Murdzek, J . S.; Bazan, G. C.; Robbins, J .; DiMare,
M.; O’Regan, M. J . Am. Chem. Soc. 1990, 112, 3875-3886.
(2) Fu, G. C.; Nguyen, S. T.; Grubbs, R. H.; Ziller, J . W. J . Am. Chem.
Soc. 1993, 115, 9856-9857.
(3) Schrock, R. R. Tetrahedron 1999, 55, 8141-8153.
(4) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997,
36, 2036-2055.
(5) Fu¨rstner, A. Angew. Chem., Int. Ed. 2000, 39, 3013-3043.
(6) Armstrong, S. K. J . Chem. Soc., Perkin Trans. 1 1998, 371-388.
(7) Nakamura, I.; Yamamoto, Y. Chem. Rev. 2004, 104, 2127-2198.
(8) Deiters, A.; Martin, S. F. Chem. Rev. 2004, 104, 2199-2238.
(9) Tolstikov, A. G.; Tolstikov, G. A. Russ. Chem. Rev. 1993, 62, 579-
601.
(10) Postema, M. H. D. C-Glycoside Synthesis, 1st ed.; CRC Press:
Boca Raton, FL, 1995.
(11) Levy, D. E.; Tang, C. The Chemistry of C-Glycosides; Perga-
mon: Oxford, 1995.
(19) Tuyen Nguyen, V.; De Kimpe, N. Tetrahedron Lett. 2004, 45,
3443-3446.
(20) van Otterlo, W. A. L.; Pathak, R.; de Koning, C. B. Synlett 2003,
1859-1861.
(21) Schmidt, B.; Wildemann, H. Eur. J . Org. Chem. 2000, 3145-
(12) Gurjar, M. K.; Krishna, L. M.; Reddy, B. S.; Chorghade, M. S.
Synthesis 2000, 557-560.
3163.
(22) Nicolaou, K. C.; Veale, C. A.; Hwang, C.-K.; Hutchinson, J .;
Prasad, C. V. C.; Ogilvie, W. W. Angew. Chem., Int. Ed. Engl. 1991,
30, 299-303.
(13) Williams, D. R.; Cortez, G. S.; Bogen, S. L.; Rojas, C. M. Angew.
Chem., Int. Ed. 2000, 39, 4612-4615.
(14) Rainier, J . D.; Allwein, S. P. J . Org. Chem. 1998, 63, 5310-
(23) Leeuwenburgh, M. A.; Overkleeft, H. S.; van der Marel, G. A.;
van Boom, J . H. Synlett 1997, 1263-1264.
(24) Oguri, H.; Tanaka, S.; Oishi, T.; Hirama, M. Tetrahedron Lett.
2000, 41, 975-978.
5311.
(15) Sturino, C. F.; Wong, J . C. Y. Tetrahedron Lett. 1998, 39, 9623-
9626.
(16) Calimente, D.; Postema, M. H. D. J . Org. Chem. 1999, 64,
1770-1771.
(25) Trost, B. M.; Brown, B. S.; McEachern, E. J .; Kuhn, O. Chem.s
Eur. J . 2003, 9, 4442-4451.
(17) Rainier, J . D.; Allwein, S. P.; Cox, J . M. J . Org. Chem. 2001,
66, 1380-1386.
(26) Ali, M. S.; Tezuka, Y.; Banskota, A. H.; Kadota, S. J . Nat. Prod.
2001, 64, 491-496.
(18) van Otterlo, W. A. L.; Ngidi, E. L.; de Koning, C. B. Tetrahedron
Lett. 2003, 44, 6483-6486.
(27) Prasain, J . K.; Tezuka, Y.; Li, J . X.; Tanaka, K.; Basnet, P.;
Dong, H.; Namba, T.; Kadota, S. Planta Med. 1999, 65, 196-196.
10.1021/jo048937w CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/30/2004
7672
J . Org. Chem. 2004, 69, 7672-7687

Ruthenium-Catalyzed Olefin Isomerization
SCHEME 1. En ol Eth er Meta th esis ver su s
Tw o-Step Allyl Eth er Meta th esis/Isom er iza tion
P r otocol
nonmetathesis tandem reactions require a change in the
nature of the catalytically active species, which may be
induced by the addition of appropriate reagents to the
reaction mixture after the completion of the metathesis
step. A ring-closing metathesis olefin isomerization se-
quence has been independently developed along the lines
of this concept by Snapper et al.38 and by us.39,40
In this contribution, we provide a full account of our
work on the tandem ring-closing metathesis olefin isomer-
ization sequence. Scope and limitations of the method are
evaluated for four different protocols developed in our
laboratory, and some mechanistic considerations based
on 31P NMR and 1H NMR spectroscopical studies are
presented.
SCHEME 2. Syn th etic Str a tegy for Cyclic
Dia r ylh ep ta n oid A
Resu lts a n d Discu ssion
Syn th esis of Sta r tin g Ma ter ia ls. We prepared a set
of starting dienes 2a -w to evaluate the scope and
limitations of the method (Chart 1).
Allyl ethers 2a -m , 2t, and 2u were obtained by
allylation of the sodium salts of the corresponding alco-
hols 1a -m , 1t, and 1u , respectively, with allyl bromide
(Scheme 3).
These alcohols have been prepared by addition of the
appropriate Grignard reagent (n ) 0, vinyl; n ) 1, allyl;
n ) 2, butenyl magnesium halide) to the corresponding
aldehyde or ketone, except for 1d , 1h , 1i, and 1t. 1d was
synthesized by lithiation of 2,3-dihydropyran with tert-
BuLi and trapping the resulting vinyllithium with ac-
roleine (eq 1).41
that involves an intermolecular Heck arylation as the key
C-C bond-forming step. This strategy obviously requires
cyclic enol ether B and an appropriate arylating agent
C as starting materials (Scheme 2).28
Our need for an efficient approach to cyclic enol ethers
and recent reports in the literature describing double-
bond isomerization as an undesired side reaction of olefin
metathesis29-34 inspired a novel synthesis of these het-
erocycles that combines the advantages of enol ether
metathesis and the two-step RCM isomerization protocol.
At the same time, the disadvantages of both methods are
eliminated. Conceptually, this novel synthesis of cyclic
enol ethers is a tandem reaction consisting of one RCM
step and a nonmetathesis transformation35 (here, olefin
isomerization) mediated by a single-site catalyst. In
contrast to the well-established metathesis tandem re-
actions, such as the ring-opening-ring-closing cross
metathesis sequence,36,37 where all of the steps are
catalyzed by a ruthenium carbene species, metathesis-
1h was obtained from 1g by vanadium-catalyzed epoxi-
dation with tert-butyl hydroperoxide as a 2:1 mixture
of diastereoisomers. Remarkably, no epoxidation of the
homoallylic double bond was observed (eq 2).
1i was prepared in a three-step procedure from methyl
cinnamate by dihydroxylation with AD-mix â to give 3,
which was protected as a cyclic acetal 4.42 4 was con-
verted to a 3:2 mixture of diastereomers of 1i by a one-
pot reduction of the ester group and in situ trapping of
the resulting aldehyde with allylmagnesium bromide
(Scheme 4).
1t was analogously obtained from ester 5 (synthesized
by benzylation of butyl glycolate with NaH and benzyl
bromide, Scheme 5).
(28) Schmidt, B. Chem. Commun. 2003, 1656-1657.
(29) Bourgeois, D.; Pancrazi, A.; Nolan, S. P.; Prunet, J . J . Orga-
nomet. Chem. 2002, 643-644, 247-252.
(30) Fu¨rstner, A.; Thiel, O. R.; Ackermann, L.; Schanz, H.-J .; Nolan,
S. P. J . Org. Chem. 2000, 65, 2204-2207.
(31) Fu¨rstner, A.; Ackermann, L.; Gabor, B.; Goddard, R.; Lehmann,
C. W.; Mynott, R.; Stelzer, F.; Thiel, O. R. Chem.sEur. J . 2001, 7,
3236-3253.
(32) Alcaide, B.; Almendros, P.; Alonso, J . M. Chem.sEur. J . 2003,
9, 5793-5799.
2n was prepared from DL-methyl mandelate via a
tandem O-allylation Wittig rearrangement O-allylation
(33) Cadot, C.; Dalko, P. I.; Cossy, J . Tetrahedron Lett. 2002, 43,
1839-1841.
(34) Arisawa, M.; Terada, Y.; Nakagawa, M.; Nishida, A. Angew.
Chem., Int. Ed. 2002, 41, 4732-4734.
(38) Sutton, A. E.; Seigal, B. A.; Finnegan, D. F.; Snapper, M. L. J .
Am. Chem. Soc. 2002, 124, 13390-13391.
(39) Schmidt, B. Eur. J . Org. Chem. 2003, 816-819.
(40) Schmidt, B. Chem. Commun. 2004, 742-743.
(41) Lebouc, A.; Delaunay, J .; Riobe´, O. Synthesis 1979, 610-613.
(42) Palomo, C.; Oiarbide, M.; Landa, A. J . Org. Chem. 2000, 65,
41-46.
(35) Alcaide, B.; Almendros, P. Chem.sEur. J . 2003, 9, 1259-1262.
(36) Arjona, O.; Csaky, A. G.; Plumet, J . Eur. J . Org. Chem. 2003,
611-622.
(37) Connon, S. J .; Blechert, S. Angew. Chem., Int. Ed. 2003, 42,
1900-1923.
J . Org. Chem, Vol. 69, No. 22, 2004 7673

Schmidt
CHART 1
SCHEME 3. P r ep a r a tion of Sta r tin g Dien es 2a -m ,
SCHEME 5. Tw o-Step Syn th esis of 1ta
2t, a n d 2u a
a
Reagents and conditions: (i) NaH, THF, 65 °C, then add allyl
bromide, 65 °C (74-99%; see Supporting Information for details).
a
Reagents and conditions: (i) NaH, BnBr, THF (53%); (ii)
SCHEME 4. Th r ee-Step Syn th esis of 1ia
DIBAL-H, H2CdCHCH2MgBr (69%).
SCHEME 6. Syn th esis of 2q-s, 2v, a n d 2w a
a
a
Reagents and conditions: (i) DIBAL-H, H2CdCHMgCl (ref 45);
Reagents and conditions: (i) AD-mix â-tert-BuOH/water (100%);
(ii) DIBAL-H, H2CdCHCH2MgBr (90%); (iii) H2CdCHMgCl (3
equiv) (ref 45); (iv) NaH, TBDMSCl (85% of 2r , 95% of 2w ).
(ii) Me2C(OMe)2, p-TSA (72%); (iii) DIBAL-H, H2CdCHCH2MgBr
(81%).
(Scheme 6); one-pot reduction of the ester group with
DIBAL-H and in situ trapping of the aldehyde with
vinylmagnesium chloride or allylmagnesium bromide
gives dienes 2q and 2v, respectively, as 5:1 mixtures of
diastereomers. Only the major diastereomer is depicted.
The observed diastereoselectivity originates from chela-
tion control, as outlined previously.21,44 2r and 2w were
sequence. This compound is the precursor of 2o, which
was obtained by reduction of the ester group with
LiAlH4.43 Methylation of 2o with NaH and methyl iodide
yields 2p . Compound 6, which was synthesized by
allylation of methyl mandelate in the presence of silver
oxide, serves as a precursor for substrates 2q-s,v,w
(43) Schmidt, B.; Wildemann, H. J . Chem. Soc., Perkin Trans. 1
2000, 2916-2925.
(44) Schmidt, B.; Wildemann, H. Synlett 1999, 1591-1593.
7674 J . Org. Chem., Vol. 69, No. 22, 2004

Ruthenium-Catalyzed Olefin Isomerization
SCHEME 7. Ru -Ca ta lyzed RCM a n d Rh -Ca ta lyzed
Isom er iza tion a
SCHEME 8. Attem p ts tow a r d Selective
Isom er iza tion of 7k a
a
Reagents and conditions: (i) [Cl2(PCy3)2RudCHPh] (2 mol %),
DCM (89% of 7f, 95% of 7k ); (ii) [ClRh(PPh3)3] (5 mol %), DBU
(2 equiv), ethanol, 78 °C (79% of 8f, 91% of a 1:1 mixture of 8k
and 9k ).
a
Reagents and conditions: (i) KO-tert-Bu, DMSO, 120 °C (75%
of a 4:1 mixture of 9k and 8k ); (ii) [RuCl2(PPh3)3] (2.7 mol %),
NaBH4 (25 mol %), methanol, 65 °C (41% of 8k and 21% of 10k ).
synthesized from 2q and 2v, respectively, by silylation
with TBDMS chloride. Triene 2s was obtained by addi-
tion of excess vinylmagnesium chloride to 6, as previously
described in the literature.44,45
SCHEME 9. RCM Isom er iza tion : Sin gle-Site
Ca ta lyst Con cep t
RCM Isom er iza tion a s Tw o-Step P r oced u r es. We
originally envisaged a two-step procedure for the syn-
thesis of cyclic enol ethers, consisting of the ruthenium-
catalyzed ring-closing metathesis of allyl ethers 2, fol-
lowed by a rhodium-catalyzed isomerization of the
resulting dihydropyrans 7 to the cyclic enol ethers 8. For
the isomerization step, a method originally introduced
by Corey for the deprotection of allyl ethers was adapted
and uses Wilkinson’s catalyst in the presence of a base.46
A similar isomerization protocol has more recently been
applied to cyclic allyl ethers.23,24,47 In our work, 7f was
converted to 8f in good yield and regioselectivity in the
presence of 5 mol % [RhCl(PPh3)3] and 2 equiv of DBU.
It was not possible to reduce the amount of catalyst or
base without significant loss of activity. Furthermore, the
transformation occasionally failed completely, and it is
not possible for us to give an explanation for this
unreliability. The 2-furyl-substituted dihydropyran 7k is
also isomerized in excellent yield. Regioselectivity, how-
ever, is poor as a 1:1 mixture of 8k and the higher-
substituted enol ether 9k results under these conditions
(Scheme 7).
Two alternative isomerization procedures were tested
for 7k . A base-induced variant, using KO-tert-Bu in
DMSO,22 gives the undesired higher-substituted regio-
isomer 9k as the major product along with approximately
20% of 8k . We then considered an isomerization protocol
originally developed by Frauenrath that uses the conve-
niently available complex [RuCl2(PPh3)3] in combination
with NaBH4 in methanol as a solvent.48 Presumably, a
Ru-hydride complex is formed in situ, which mediates
olefin isomerization reactions via a hydrometalation/
â-hydride elimination pathway.49 It should be mentioned
in this context that a variety of examples for olefin
isomerization reactions with defined Ru-H complexes
has also been published in the literature.18,25,50-52 In our
work, application of Frauenrath’s protocol to 7k resulted
in the formation of 8k and tetrahydropyran 10k in a 2:1
ratio. The undesired regioisomer 9k could not be detected
by NMR spectroscopy. Scheme 8 summarizes these
attempts toward the regioselective isomerization of 7k .
Ta n d em RCM Isom er iza tion Med ia ted by Sin gle-
Site Ca ta lysts. Th e Con cep t. The combination of
metathesis and nonmetathesis steps of tandem sequences
requires either the use of compatible catalysts53,54 or a
change in the reactivity of a single-site catalyst. For
tandem olefin metathesis hydrogenation, the single-site
catalyst concept has been achieved by replacing the inert
gas atmosphere by an atmosphere of hydrogen.55-61 The
reaction of Grubbs’ catalyst [Cl2(PCy3)2RudCHPh] with
hydrogen leads to a Ru-H complex,62 which effectively
catalyzes olefin hydrogenation and olefin isomerization.63
Thus, a successful realization of an RCM isomerization
sequence requires the conversion of the carbene complex
to a ruthenium-hydride complex with simultaneous
supression of the undesired hydrogenation (Scheme 9).
Snapper et al. achieved this goal by setting the reaction
mixture under an atmosphere of highly diluted hydrogen
(51) Wakamatsu, H.; Nishida, M.; Adachi, N.; Mori, M. J . Org.
Chem. 2000, 65, 3966-3970.
(52) Krompiec, S.; Pigulla, M.; Bieg, T.; Szczepankiewicz, W.;
Kuznik, N.; Krompiec, M.; Kubicki, M. J . Mol. Catal. A 2002, 189, 169-
185.
(53) Cossy, J .; Bargiggia, F. C.; BouzBouz, S. Org. Lett. 2003, 5, 459-
462.
(54) Grigg, R.; Sridharan, V.; York, M. Tetrahedron Lett. 1998, 39,
4139-4142.
(55) Louie, J .; Bielawski, C. W.; Grubbs, R. H. J . Am. Chem. Soc.
2001, 123, 11312-11313.
(56) Bielawski, C. W.; Louie, J .; Grubbs, R. H. J . Am. Chem. Soc.
2000, 122, 12872-12873.
(45) Schmidt, B.; Wildemann, H. J . Org. Chem. 2000, 65, 5817-
5822.
(57) Watson, M. D.; Wagener, K. B. Macromolecules 2000, 33, 3196-
3201.
(46) Corey, E. J .; Suggs, J . W. J . Org. Chem. 1973, 38, 3224.
(47) van Hooft, P. A. V.; El Oualid, F.; Overkleeft, H. S.; van der
Marel, G. A.; van Boom, J . H.; Leeuwenburgh, M. A. Org. Biomol.
Chem. 2004, 2, 1395-1403.
(58) Drouin, S. D.; Zamanian, F.; Fogg, D. E. Organometallics 2001,
20, 5495-5497.
(59) Børsting, P.; Nielsen, P. Chem. Commun. 2002, 2140-2141.
(60) Fu¨rstner, A.; Leitner, A. Angew. Chem., Int. Ed. 2003, 42, 308-
311.
(48) Frauenrath, H.; Runsink, J . J . Org. Chem. 1987, 52, 2707-
2712.
(61) Schmidt, B.; Pohler, M. Org. Biomol. Chem. 2003, 1, 2512-
2517.
(62) Drouin, S. D.; Yap, G. P. A.; Fogg, D. E. Inorg. Chem. 2000, 39,
5412-5414.
(63) Schmidt, B. Eur. J . Org. Chem. 2004, 1865-1880.
(49) McGrath, D. V.; Grubbs, R. H. Organometallics 1994, 13, 224-
235.
(50) Curran, D. P.; J acobs, P. B.; Elliott, R. L.; Kim, B. H. J . Am.
Chem. Soc. 1987, 109, 5280-5282.
J . Org. Chem, Vol. 69, No. 22, 2004 7675

Schmidt
after completion of the metathesis step.38 We investigated
four different additives used to activate the metathesis
catalyst for the isomerization step. The results obtained
for each protocol are summarized and discussed in the
following paragraphs.
SCHEME 10. Ta n d em RCM Isom er iza tion :
Activa tion of th e Ru Ca ta lyst w ith Eth yl Vin yl
Eth er a
Activa tion by Ad d ition of Eth yl Vin yl Eth er .
Grubbs et al. recently described the formation of “Fischer-
type” carbene complexes derived from [Cl2(PCy3)2-
RudCHPh] (11a ) by treatment of this complex with
electron-rich alkenes, such as ethyl vinyl ether.64 In this
case, metathetic exchange of the benzylidene ligand
occurs with the formation of the new carbene complex
[Cl2(PCy3)2RudCHOEt] (11b), which when heated, de-
composes to the hydride complex [Cl(CO)(PCy3)2Ru-H]
(12). We assumed that the propagating species of the
RCM of dienes 2, [Cl2(PCy3)2RudCH2] (11c), would also
undergo metathetical exchange with ethyl vinyl ether to
give 11b. In a first experiment, diene 2f was cyclized
using 5 mol % [Cl2(PCy3)2RudCHPh] (11a ) in toluene.
Ring-closing metathesis is complete under these condi-
tions within 20 min, and 31P NMR reveals the presence
of [Cl2(PCy3)2RudCH2] (11c, δ(31P) ) 44 ppm).65 Addition
of ethyl vinyl ether led to a rapid disappearance of the
signal at 44 ppm, and a new signal at 37 ppm, which is
indicative for the Fischer-type carbene complex 11b,64
was observed. Subsequent heating of the reaction mix-
ture to reflux induced a color change from deep red to
orange yellow, and simultaneously, a new signal in the
31P NMR spectrum appeared at 48 ppm, which is in good
agreement with the literature value for hydride complex
12.64 Although a hydride complex is obviously formed,
isomerization of the intermediate metathesis product 7f
to enol ether 8f is very slow; after 8 h in refluxing toluene,
only 10% of 8f and 90% of 7f could be detected in the
proton NMR spectrum of the crude reaction mixture. A
similar result was obtained for 2l. In contrast to these
six-membered heterocycles, five-membered oxacycles are
isomerized to the corresponding enol ethers in prepara-
tively useful rates of conversion and isolated yields. Thus,
when dienes 2a -e were subjected to the protocol outlined
above, quantitative conversion to the corresponding cyclic
enol ethers was observed within 5-7 h. Except for 2e,
which has a quaternary center in the 2-position, the RCM
isomerization sequence results in the formation of re-
gioisomers 8 and 9 in a 4:1 ratio. In the case of 2a , the
selectivity for the formation of the less-substituted cyclic
enol ether 8a was significantly better, probably due to
steric effects. Ratios of regioisomers were determined by
1H NMR spectroscopy of the crude reaction mixture.
Isolated yields, however, refer to pure 8 because the
regioisomers 9 decompose selectively upon chromatog-
raphy on silica. Scheme 10 and Table 1 summarize the
results.
a
Reagents and conditions: (i) toluene, [Cl2(PCy3)2RudCHPh]
(5 mol %), 25 °C, add EtOCHdCH2 after completion of the
metathesis reaction, 25 °C for 10 min, and then 110 °C (see Table
1 for details).
TABLE 1. Ta n d em RCM Isom er iza tion : Activa tion of
th e Meta th esis Ca ta lyst w ith Eth yl Vin yl Eth er
a
b
Isolated yield of pure 8. With <10% conversion after 10 h.
Frauenrath for the development of an olefin isomeriza-
tion protocol that relies on the formation of a ruthenium-
hydride complex from [RuCl2(PPh3)3] and NaBH4 in
situ.48,71,72 To the best of our knowledge, the reaction of
Activa tion by Ad d ition of In or ga n ic Hyd r id es. It
is known that complex hydrides, especially NaBH4,
reduce Ru(II) or Ru(III) compounds to Ru-hydride
complexes.66-70 This observation has been exploited by
(69) Young, R.; Wilkinson, G. Inorg. Synth. 1977, 17, 75-77.
(70) Bennett, M. A.; Bruce, M. I.; Matheson, T. W. In Comprehensive
Organometallic Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E. W.,
Eds.; Pergamon Press: Oxford, 1982; Vol. 4, pp 692-820.
(71) Frauenrath, H.; Philips, T. Angew. Chem., Int. Ed. Engl. 1986,
25, 274-275.
(72) Bennett, M. A.; Matheson, T. W. In Comprehensive Organome-
tallic Chemistry; Wilkinson, G., Stone, F. G. A., Abel, E. W., Eds.;
Pergamon Press: Oxford, 1982; Vol. 4, pp 932-965.
(64) Louie, J .; Grubbs, R. H. Organometallics 2002, 21, 2153-2164.
(65) Schwab, P.; Grubbs, R. H.; Ziller, J . W. J . Am. Chem. Soc. 1996,
118, 100-110.
(66) Harris, R. O.; Hota, N. K.; Sadavoy, L.; Yuen, J . M. C. J .
Organomet. Chem. 1973, 54, 259-264.
(67) Holah, D. G.; Hughes, A. N.; Hui, B. C. Can. J . Chem. 1976,
54, 320-328.
(68) Peet, W. G.; Gerlach, D. H. Inorg. Synth. 1974, 15, 38-42.
7676 J . Org. Chem., Vol. 69, No. 22, 2004

Ruthenium-Catalyzed Olefin Isomerization
Grubbs’ catalyst [Cl2(PCy3)2RudCHPh] with NaBH4 has
not been investigated so far. We assumed that introduc-
tion of a hydride by nucleophilic attack might take place,
which should give an isomerization-active Ru-H species.
In an initial experiment, NaBH4 (0.5 equiv) was added
to a completed metathesis reaction of substrate 2f in
toluene. When the mixture was heated to reflux, slow
conversion of the RCM product 7f to the cyclic enol ether
8f was observed, which was complete after 8 h. 8f was
obtained with a regioselectivity better than 95:5, and no
isomer 9f could be detected in the NMR spectrum of the
crude reaction mixture. The use of NaH was found to
reduce the reaction times slightly without affecting yields
and selectivities. In contrast, addition of DIBAL-H (0.5
equiv) resulted in an incomplete conversion of the
primary metathesis product to the cyclic enol ether 8f.
Scope and limitations of this protocol have been evaluated
for the examples listed in Table 2. Only for dihydrofurans
8a -d were significant amounts of the higher-substituted
regioisomers 9 observed. Ratios of regioisomers 8 and 9
are in the same range as those observed for the products
obtained via the ethyl vinyl ether protocol (Table 1),
except for 8d , which has a donor atom in the side chain.
It might be speculated that the dihydropyran substituent
coordinates to the isomerization catalyst and exerts a
directing effect, resulting in a larger amount of 9d . With
this protocol, isomerization of the five-membered hetero-
cycles is normally complete within 2-3 h. For six-
membered oxacycles 8f-t, reaction times are generally
longer (normally in the range of 5-7 h), but the higher-
substituted dihydropyrans 9 are normally not observed
with olefin metathesis is often attributed to ruthenium-
hydride species that either are present in the precatalyst
as an impurity31 or result from unimolecular decomposi-
tion of the propagating species.73,74 It was therefore
necessary to check whether an activating reagent is
required to induce isomerization activity. To this end, 2a
was reacted with 5 mol % Grubbs’ catalyst 11a in toluene
and then heated to reflux for 5 h. A sample of the reaction
mixture was analyzed by 1H NMR spectroscopy and
found to contain exclusively the metathesis product 7a .
Isomerization product 8a or 9a could not even be detected
in trace amounts. When 30 mol % NaBH4 was added to
the residual reaction mixture and the mixture was heated
to reflux, complete isomerization of 7a to 8a and 9a (8:1
ratio) occurred in <2 h. (c) Does the isomerization occur
with racemization? As mentioned above, we have ob-
served minor amounts of isomerized dihydropyrans 13
in two cases. Isomerization of 13 might give either 7 or
achiral 9. If enantiomerically pure starting materials are
employed in the sequence, racemization might occur
when the double bond in enol ethers 9 migrates (via 13
and 7) to give 8, which then would obviously be a racemic
mixture (Scheme 12). This scenario appears to be quite
unlikely since no significant amounts of products 9
(except for 2k ) could be detected in the case of dihydro-
pyrans. Furthermore, the higher-substituted enol ethers
9 can be expected to be the thermodynamically preferred
products.
Nevertheless, the sequence was repeated for enantio-
merically enriched (R)-2f, which was obtained from
(R)-1f. This homoallylic alcohol was synthesized in 90%
ee via allylboration following a literature procedure.75
(R)-2f, subjected to the conditions of the tandem RCM
isomerization process, yields (R)-8f with the same enan-
tiomeric excess determined for the homoallylic alcohol.
This control experiment has also been conducted by
Snapper et al. for their protocol with the same result.38
Furthermore, dienes 2h and 2i, which have been used
as mixtures of diastereomers, are converted to 8h and
8i, respectively, without alteration of the diastereomeric
ratio. From these observations, we conclude that the
racemization scenario outlined in Scheme 12 does not
play a significant role in this tandem process.
1
in the H NMR spectrum of the crude reaction mixture.
An exception is 2-furyl-substituted 8k , which was ob-
tained with approximately 10% of its regioisomer 9k .
Ethers, epoxides, acetals, and silyl ethers are compatible
with the reaction conditions. No conversion was observed
for unprotected alcohols, and incomplete conversion was
observed for 8g, 8j, and 8m . 8g was obtained after
prolonged heating with 30% of RCM product 7g. We
speculate that intramolecular coordination of the exocy-
clic double bond to the ruthenium center occurs, resulting
in an inhibition of the catalytically active species. Ap-
plication of the protocol to 2j and 2m results in incom-
plete isomerization of the intermediate dihydropyrans 7j
and 7m to the cyclic enol ethers 8j and 8m , respectively.
In these cases, the isomers 13j and 13m were obtained
as byproducts; isomers 9j and 9m , however, could not
be detected (Scheme 11).
At this point, control experiments were conducted to
address three questions. (a) Is the isomerization really
ruthenium-catalyzed or probably a base-induced process?
To answer this question, which arises in those cases
where the strong base NaH is used as an activating
agent, 7a was synthesized by ring-closing metathesis of
2a , purified by flash chromatography, and then distilled.
This purification should be sufficient for removing any
ruthenium residues. Pure, colorless 7a was then treated
with 1 equiv of NaH in refluxing toluene for several
hours. Upon hydrolysis and evaporation of the solvent,
1H NMR analysis of the mixture revealed the absence of
any isomerized products 8a or 9a . The starting material,
7a , was recovered unchanged in quantitative yield. (b)
Is an activating agent really required for isomerization
activity? The interference of isomerization side reactions
To gain some insight into the nature of the isomeriza-
tion catalyst, the tandem sequence was monitored by 31
P
NMR for the example of diene 2p . After ring-closing
metathesis of 2p was completed, a signal at 43.8 ppm
was observed, which can be assigned to the methylidene
complex 11c. When NaBH4 is added and the mixture
heated to reflux, this signal disappears within 1 h and a
new species is formed with a 31P NMR resonance at 47.1
ppm. This signal is still observed after the isomerization
step is complete. Ruthenium-hydride species could be
detected by repeating the reaction in perdeuterated
toluene with 20 mol % catalyst 11a . The high-field region
of the NMR spectrum obtained from the reaction mixture
shows three signals originating from the ruthenium-
hydride species: a broad signal at -7.58 ppm, a doublet
with a coupling constant of 43 Hz at -10.63 ppm, and a
(73) Ulman, M.; Grubbs, R. H. J . Org. Chem. 1999, 64, 7202-7207.
(74) Hong, S. H.; Day, M. W.; Grubbs, R. H. J . Am. Chem. Soc. 2004,
126, 7414-7415.
(75) Ram Reddy, M. V.; Brown, H. C.; Ramachandran, P. V. J .
Organomet. Chem. 2001, 624, 239-243.
J . Org. Chem, Vol. 69, No. 22, 2004 7677

Schmidt
TABLE 2. RCM Isom er iza tion Sequ en ce: Activa tion of th e Meta th esis Ca ta lyst w ith In or ga n ic Hyd r id es (P r otocol a )
or Isop r op a n ol/Ba se (P r otocol b)
7678 J . Org. Chem., Vol. 69, No. 22, 2004

Ruthenium-Catalyzed Olefin Isomerization
Ta ble 2 (Con tin u ed )
a
Reagents and conditions: toluene (0.2 M), [Cl2(PCy3)2RudCHPh] (5 mol %), 25 °C, and then add NaH or NaBH4 (50 mol %), 110 °C
b
(complete conversion was observed after 5 h for 8a -e, 8 h for 8f-t, and 10 h for 8u ,w , unless otherwise stated). Reagents and conditions:
toluene (0.2 M), [Cl2(PCy3)2RudCHPh] (5 mol %), 25 °C, and then add 2-propanol (25% v/v) and NaOH (50 mol %), 110 °C (complete
conversion was observed after 2 h for all examples except 8k (1 h) and 8s (7 h)). c Complex mixture of products. Reaction stops at 70%
d
conversion. e Obtained as an inseparable mixture with 10% of 8f and an unidentified byproduct. f Dienes 2 are 3:2 mixtures of
g
h
diastereoisomers; products 8 are obtained with the same diastereomeric ratio. Incomplete conversion. Incomplete conversion, 10:4:1
ratio of products 8m , 7m and 13m . Only RCM product 7 observed. Obtained with 10% of 10. [Cl2(PCy3)2RudCHPh] (8 mol %) and
i
j
k
longer reaction times required.
triplet with a coupling constant of 18 Hz at -14.24 ppm.
Although the exact structure of the ruthenium-hydride
species involved is not clear, it is most likely that the
triplet originates from a complex containing two phos-
phine ligands. The observed coupling constant of 18 Hz
is in good agreement with literature values reported for
other Ru-H complexes.64,76 The experiment was repeated
without addition of NaBH4 or any other additive to check
if the observed signals originate from an impurity present
in the precatalyst or from decomposition products result-
ing from monomolecular degradation of the propagating
species after completion of the metathesis reaction. After
the substrate was heated in the presence of 20 mol %
precatalyst 11a for 2 h, no trace of isomerized products
was observed and the high-field region of the NMR
spectrum did not show any signals that might be as-
signed to Ru-hydride species.
Activa tion by Ad d ition of 2-P r op a n ol a n d Ba se.
The development of this protocol has been inspired by
(76) Christ, M. L.; Sabo-Etienne, S.; Chaudret, B. Organometallics
1994, 13, 3800-3804.
J . Org. Chem, Vol. 69, No. 22, 2004 7679

Schmidt
SCHEME 11. P r od u ct Distr ibu tion for Ta n d em
RCM Isom er iza tion of 2j,m a
tions for the examples listed in Table 2. Surprisingly, the
first example, 2a , which undergoes the tandem sequence
readily with both protocols discussed above, does not
react to 8a cleanly under these conditions. Instead, a
3:2:1 mixture of 8a , tetrahydrofuran 10a , and the higher-
substituted regioisomer of 8a , 9a is obtained. The forma-
tion of tetrahydrofuran 10a is quite interesting because
this is obviously the product of a hydrogen transfer from
2-propanol to either 7a , 8a , or 9a . Hydrogen transfer
from alcohols to alkenes is a known process but com-
paratively rare.84 We assumed that hydrogenation is
facilitated for five-membered ring systems and, therefore,
did not investigate this protocol for substrates 2b-e. All
other substrates listed in Table 2 that undergo the
tandem RCM isomerization process mediated by inor-
ganic hydrides also react to enol ethers 8 using the
2-propanol/NaOH additive combination. Reaction times
are significantly reduced and are normally in the range
of 2-3 h. Isolated yields are comparable, and regioselec-
tivities are generally excellent. However, the use of
2-propanol/NaOH does not lead only to reduced reaction
times. A range of substrates that undergo no or only
incomplete isomerization with the inorganic hydride
protocol react smoothly under these conditions. For
instance, tandem RCM isomerization of 2g using NaH
as an additive resulted in the formation of a 7:3 mixture
of 7g and 8g, and addition of 2-propanol/NaOH results
in complete conversion of 7g to 8g. Interestingly, 8f,
resulting from a hydrogenation of the exocyclic double
bond, is formed as an inseparable byproduct. Similarly,
2j and 2m , which do not give 8j and 8m in preparatively
useful yields and selectivities if inorganic hydrides are
added, undergo quantitative conversion in excellent
selectivities under the present conditions. The inorganic
hydride protocol also fails for 2s as only the RCM product
7s was obtained. Application of the 2-propanol/NaOH
protocol to this substrate yields, surprisingly, dihydro-
pyran 8s, where the exocyclic double bond is hydroge-
nated. Monitoring the conversion of 2s to 8s by NMR
spectroscopy reveals that the primary metathesis product
7s (formed as a 4:1 mixture of diastereomers)45 first
undergoes hydrogenation of the exocyclic double bond
(giving intermediate 14) which then isomerizes slowly to
8s. Thus, formation of 8s can be described as a tandem
RCM transfer hydrogenation-isomerization reaction.
a
Reagents and conditions: (i) toluene, [Cl2(PCy3)2RudCHPh]
(5 mol %), 25 °C, add NaH after completion of the metathesis
reaction, 110 °C for 8 h (74% of a 12:1:1 8j/7j/13j mixture, 100%
of a 10:4:1 8m/7m/13m mixture).
SCHEME 12. P oten tia l Ra cem iza tion P a th w a y
recent reports that Grubbs’ catalyst (11a ), like other
ruthenium complexes,77-79 mediates transfer hydrogena-
tion and dehydrogenation80 in the presence of secondary
alcohols and ketones, respectively.55,81 It is believed that
ruthenium-hydrides are the catalytically active species
in these transformations, and that they are formed by
â-hydride elimination of a ruthenium-alkoxide. Thus, we
assumed that addition of a secondary alcohol and a base
to a completed metathesis reaction should induce a
conversion of the ruthenium-carbene species to a ru-
thenium-hydride species. To test this hypothesis, 2-pro-
panol and K2CO3 (as a base) were added to a completed
metathesis reaction of 2k in toluene. When the mixture
was heated, slow formation of the isomerized product 8k
was observed by TLC. Use of triethylamine as a base also
resulted in the slow but incomplete formation of 8k .
However, addition of 2-propanol and solid NaOH to the
reaction mixture turned out to be very effective; under
these conditions, the intermediate RCM product 7k was
converted quantitatively to 8k within 1 h in excellent
regioselectivity. The reaction time is significantly re-
duced, compared to that of the protocol based on catalyst
activation by inorganic hydrides; for this example, 5 h is
required to achieve complete conversion. It has recently
been reported by Dinger and Mol that primary alcohols
in the presence of a base also react with Grubbs’ catalyst
to yield ruthenium-hydride complexes.82,83 Therefore,
methanol and ethanol were also tested instead of 2-pro-
panol, but they turned out to be significantly less
effective. In these cases, incomplete isomerization was
observed. Having established the protocol for the conver-
sion of 2k f 8k , we investigated the scope and limita-
Apart from the functional groups tolerated by the
inorganic hydride protocol, activation of the catalyst with
2-propanol/NaOH allows the use of esters (2n f 8n )
and unprotected primary (2o f 8o) and secondary (2q
f 8q) alcohols. As for the conversion of tertiary alcohol
2s, transfer hydrogenation interferes with the isomer-
ization step. Carefully monitoring the reaction by TLC
allows the isolation of 8o and 8q in preparatively use-
ful yields and selectivities; application of the protocol to
(77) Sasson, Y.; Blum, J . J . Org. Chem. 1975, 40, 1887-1896.
(78) J ohnson, J . B.; Ba¨ckvall, J .-E. J . Org. Chem. 2003, 68, 7681-
7684.
(79) Ito, M.; Osaku, A.; Kitahara, S.; Hirakawa, M.; Ikariya, T.
Tetrahedron Lett. 2003, 44, 7521-7523.
(80) Gladiali, S.; Mestroni, G. In Transition Metals for Organic
Synthesis; Beller, M., Bolm, C., Eds.; Wiley-VCH: Weinheim, Germany,
1998; Vol. 2, pp 97-119.
(81) (a) Cho, C. S.; Kim, B. T.; Choi, H.-J .; Kim, T.-J .; Shim, S. C.
Tetrahedron 2003, 59, 7997-8002. (b) Cho, C. S.; Kim, B. T.; Kim,
H.-S.; Kim, T.-J .; Shim, S. C. Organometallics 2003, 22, 3608-3610.
(c) Cho, C. S.; Kim, B. T.; Kim, T.-J .; Shim, S. C. J . Org. Chem. 2001,
66, 9020-9022.
(82) Dinger, M. B.; Mol, J . C. Organometallics 2003, 22, 1089-1095.
(83) Dinger, M. B.; Mol, J . C. Eur. J . Inorg. Chem. 2003, 2827-
2833.
(84) Edwards, M. G.; J azzar, R. F. R.; Paine, B. M.; Shermer, D. J .;
Whittlesey, M. K.; Williams, J . M. J .; Edney, D. D. Chem. Commun.
2004, 90-91.
7680 J . Org. Chem., Vol. 69, No. 22, 2004

Ruthenium-Catalyzed Olefin Isomerization
compounds catalyzed by [Cl2(PCy3)2RudCHPh] (11a ).85
These reactions had previously been reported for other
transition-metal complexes, and it is generally believed
that activation of the Si-H bond occurs by oxidative
addition of the silane to the metal complex, giving a
metal-hydride complex.86,87 On the basis of this assump-
tion, we investigated the use of silanes to convert the
propagating species of olefin metathesis, [Cl2(PCy3)2-
RudCH2] (11c), to an isomerization catalyst. Lee et al.
reported a decreasing activity of silanes in dehydroge-
native silylation of alcohols in the order Ph2SiH2 > Me2-
PhSiH > Et3SiH. Guided by this observation, we sub-
jected 2k to the conditions of this tandem protocol
because its RCM product, 7k , was found in the protocols
discussed above to undergo isomerization significantly
faster than all other dihydropyrans. After diphenylsilane
was added to the completed metathesis reaction and the
mixture was heated, a color change from deep red to
orange yellow rapidly occurred. Simultaneously, the
signal of 11c in the 31P NMR spectrum disappeared and
two new signals at 46.2 and 34.2 ppm were observed.
However, after the reaction mixture was heated to reflux
for 4 h, it was not possible to detect any isomerization
product in the reaction mixture. Using Me2PhSiH as an
activating agent led to the rapid formation of a new
phosphorus-containing species [δ(31P) ) 46.5 ppm] and
the partial isomerization to the desired enol ether 8k
with 30% conversion after 7 h in refluxing toluene.
Finally, triethylsilane was found to give the most active
isomerization catalyst in this series. Although a com-
paratively long reaction time of 10 h was required, 8k
was obtained in yields and selectivities comparable to
those of the previously discussed conditions. 31P NMR
spectroscopy of the reaction mixture revealed the pres-
ence of a new signal at 47.5 ppm. The 31P NMR signals
observed for the three different silanes differ only slightly
in their chemical shift value, but the significantly distinct
isomerization activity suggests that indeed a different
species is involved in each protocol. We have applied the
optimized conditions found for the conversion of 2k f
8k to dienes 2 listed in Table 3. Only 2g gave a complex
mixture of products, which contained the desired 8g as
a major component. All other dienes that were subjected
to these conditions were converted cleanly to the cyclic
enol ethers 8 in good yields and excellent regioselectivi-
ties within 10-16 h at 110 °C. Noteworthy is the
conversion of diene 2o, which contains a primary alcohol.
This starting material was employed because we as-
sumed that Lee’s dehydrogenative silylation procedure
might be incorporated as an additional step in our
tandem sequence; after ring-closing metathesis of 2o was
completed, 1.1 equiv of triethylsilane was added to the
reaction mixture. When the mixture was heated, the
expected dehydrogenative silylation of the primary alco-
hol occurred rapidly and was completed before the
reaction mixture reached reflux temperature. The isom-
erization reaction took place subsequently over the
usual time scale of several hours in refluxing toluene,
SCHEME 13. Ta n d em RCM Isom er iza tion a n d
Su bsequ en t Tr a n sfer Hyd r ogen a tion a
a
Reagents and conditions: (i) toluene (0.2 M), [Cl2(PCy3)2-
RudCHPh] (5 mol %), 25 °C, and then add 2-propanol (25% v/v)
and NaOH (50 mol %), 110 °C, 4 h (48% of 8o and 10% of 10o);
(ii) toluene (0.2 M), [Cl2(PCy3)2RudCHPh] (5 mol %), 25 °C, and
then add 2-propanol (25% v/v) and NaOH (50 mol %), 110 °C, 0.5
h (40% of 8q); (iii) toluene (0.2 M), [Cl2(PCy3)2RudCHPh] (5 mol
%), 25 °C, and then add 2-propanol (25% v/v) and NaOH (50 mol
%), 110 °C, 8 h (46% of 10q).
2o and 2q gives first the enol ethers 8o and 8q, which
are subsequently slowly hydrogenated to tetrahydro-
pyrans 10o and 10q under the reaction conditions
(Scheme 13).
While the hydrogenation step observed for examples
2s and 2o is a true hydrogen transfer from 2-propanol
to an alkene, a mechanistic alternative must be consid-
ered for 2q; enol ether 8q might undergo isomerization
to a cyclic ketone, which then undergoes transfer hydro-
genation to yield the secondary alcohol 10q. Although we
could not observe a cyclic ketone during the reaction, we
cannot exclude this pathway. It is quite striking that
hydrogen transfer occurs as a competing or subsequent
reaction to double-bond isomerization, preferably in those
cases where an unprotected alcohol functionality is
present in the molecule. We assume that coordination of
the ruthenium catalyst to the hydroxy group occurs,
which facilitates hydrogen transfer. This aspect will be
investigated in detail in the future. As described above,
we also checked if the isomerization, according to this
protocol, was base-induced rather than ruthenium-
catalyzed. To this end, a sample of pure 7l was treated
with NaOH and 2-propanol under the reaction condi-
tions in the absence of any ruthenium compounds. No
isomerization to enol ether 8l was observed after several
hours.
Preliminary mechanistic investigations have also been
conducted for this protocol. Monitoring the reaction by
31P NMR spectroscopy reveals that the propagating
species of olefin metathesis, [Cl2(PCy3)2RudCH2] (11c),
is rapidly converted to a new phosphorus-containing
complex, which exhibits a resonance in the 31P NMR
spectrum at 51.7 ppm. In the search for a ruthenium-
hydride species, a typical isomerization sequence using
this protocol was repeated in toluene-d8. We were able
to detect two very weak resonances at -8.45 (t, J ) 22
Hz) and -10.64 ppm (d, J ) 43 Hz).
(85) Maifeld, S. V.; Miller, R. L.; Lee, D. Tetrahedron Lett. 2002,
43, 6363-6366.
(86) Lukevics, E.; Dzintara, M. J . Organomet. Chem. 1985, 295,
265-315.
Activa tion by Ad d ition of Sila n es. Recently, Lee et
al. described the dehydrogenative silylation of alcohols
and the hydrosilylation of R,â-unsaturated carbonyl
(87) Marciniec, B. In Applied Homogeneous Catalysis with Organo-
metallic Compounds; Cornils, B., Herrmann, W. A., Eds.; VCH:
Weinheim, Germany, 1996; Vol. 1, pp 487-506.
J . Org. Chem, Vol. 69, No. 22, 2004 7681

Schmidt
TABLE 3. RCM Isom er iza tion Sequ en ce: Activa tion of
th e Meta th esis Ca ta lyst w ith Tr ieth ylsila n ea
F IGURE 1. Time-conversion curve for the isomerization of
7c, with ethyl vinyl ether as the additive.
F IGURE 2. Time-conversion curve for the isomerization of
7c, with NaBH4 as the additive.
F IGURE 3. Time-conversion curve for the isomerization of
7j, with NaBH4 as the additive.
individual protocols for selected examples by analyzing
1
the composition of the reaction mixtures using H NMR
spectroscopy. Figures 1 and 2 show the isomerization step
in the tandem sequence 2c f 7c f 8c + 9c. With ethyl
vinyl ether as an additive (Figure 1), only a very short
induction period is observed, which is obviously required
for the formation of the isomerization catalyst by decom-
position of the Fischer-type carbene complex 11b. After
this induction period, a steady decrease of the concentra-
tion of RCM product 7c is observed. A significantly longer
induction period is observed for NaBH4 as the additive
(Figure 2). However, once the catalyst is formed, it
appears to be much more active than the one working in
the ethyl vinyl ether protocol. In both protocols, the ratio
of regioisomers 8c and 9c appears to be nearly constant
during the reaction.
As an example for a dihydropyran isomerization, the
tandem sequence 2j f 7j f 8j was chosen because this
transformation was found to be comparatively slow for
all protocols. Figure 3 shows the time-conversion curve
for the activation with NaBH4. For this particular
example, this protocol turns out to be inefficient; even
after 10 h, <50% of 7j was isomerized to the expected 8j
and dihydropyran 13j. Formation of the higher-substi-
tuted enol ether 9j, which is a consecutive product of 13j,
could not be observed (Scheme 14).
a
Reagents and conditions: toluene (0.2 M), [Cl2(PCy3)2-
RudCHPh] (5 mol %), 25 °C, and then add Et3SiH (1.1 equiv).
All products were obtained with regioselectivities >19:1. c Com-
b
d
plex mixture of products. Approximately 10% of 7j and 13j
present in the reaction mixture after 12 h.
making the transformation of 2o to 8x a tandem RCM
O-silylation isomerization sequence.
Close examination of the high-field region of a 1H
NMR spectrum obtained from the reaction mixture
revealed the presence of three major signals at
-10.71 (dd, J ) 43 and 8 Hz), -11.46 (d, J ) 33 Hz),
and -13.47 ppm after triethylsilane was added. On the
basis of these results, it can only be stated that, most
likely, a ruthenium-hydride species is involved, but
whether this species is different from those active in the
other protocols is not clear. It is, however, striking that
for all of the protocols where the high-field region of the
1H NMR spectrum was investigated a doublet structure
at -10.6 ppm with a coupling constant of 43 Hz was
observed.
Com p a r ison of th e P r otocols. 1H NMR-Der ived
Tim e-Con ver sion Gr a p h s for Selected Exa m p les.
Time-conversion curves have been recorded for the
7682 J . Org. Chem., Vol. 69, No. 22, 2004

Ruthenium-Catalyzed Olefin Isomerization
ration of these isomerization steps in tandem sequences.
The concept is exemplified for the regioselective synthesis
of cyclic enol ethers, which are valuable synthetic inter-
mediates. Evidence is presented that ruthenium-hydride
species are responsible for the isomerization reaction.
Currently, we are working toward application of this
novel synthetic methodology in the synthesis of target
molecules and identification of the actual isomerization
catalysts.
F IGURE 4. Time-conversion curve for the isomerization of
7j, with 2-propanol/NaOH as the additive.
Exp er im en ta l Section
Gen er a l Rem a r k s. All of the experiments were conducted
in dry reaction vessels under an atmosphere of dry argon.
Solvents were purified by standard procedures. 1H NMR
spectra were obtained at 400, 500, or 600 MHz in CDCl3, with
CHCl3 (δ ) 7.24 ppm) as an internal standard, or in C6D6,
with C6D5H (δ ) 7.18 ppm) as an internal standard. Coupling
constants (J ) are given in hertz. Signal assignments are based
on H-H correlation spectroscopy. 13C NMR spectra were
recorded at 100, 125, or 150 MHz in CDCl3, with CDCl3 (δ )
77.0 ppm) as an internal standard, or in C6D6, with C6D6 (δ )
128.0 ppm) as an internal standard. The number of coupled
protons was analyzed by DEPT or APT experiments and is
denoted by a number in parentheses following the chemical
shift value. IR spectra were recorded as films on NaCl or KBr
plates. The peak intensities are defined as strong (s), medium
(m), or weak (w). Mass spectra were obtained at 70 eV. Optical
purities were determined by HPLC using a HPLC-1050 system
equipped with a Daicel Chiralcel OD column. The following
compounds have been prepared following procedures described
in the literature: 1c,88 1d ,41 (R)-1f,75 1g,89 1l,90 1t,91 1u ,92 2e,21
2l,93 2n ,43 2o,43 2q,21 2s,45 2t,94 and 7k .95
F IGURE 5. Time-conversion curve for the isomerization of
7j, with Et3SiH as the additive.
SCHEME 14. Isom er iza tion of 7j to 8j a n d 13j
Rep r esen ta tive P r oced u r es for th e Syn th esis of Cyclic
En ol Eth er s 8. Rh odiu m -Catalyzed Dou ble-Bon d Isom er -
iza tion (P r otocol a ). To a solution of 7f (1.34 g, 7.1 mmol)
in ethanol (40 mL) were added DBU (2.24 mL, 15.0 mmol) and
[RhCl(PPh3)3] (330 mg, 5 mol %). The mixture was heated to
reflux until the starting material was fully consumed, as
indicated by TLC. All volatiles were evaporated in vacuo, and
the residue was purified by flash chromatography on silica
using cyclohexane/MTBE mixtures as eluent to give 8f (1.06
g, 79%).
R u t h en iu m -Ca t a lyzed Dou b le-Bon d Isom er iza t ion
(P r otocol b). To a solution of 7k (0.70 g, 4.7 mmol) in
methanol (20 mL) were added [RuCl2(PPh3)3] (120 mg, 2.7 mol
%) and NaBH4 (45 mg, 25 mol %). The mixture was heated to
reflux for 2 h and filtered, and the solvent was evaporated.
The residue was purified by flash chromatography on silica
to give 8k (0.29 mg, 41%) and tetrahydropyran 10k (0.15 g,
21%).
Figure 4 illustrates that the 2-propanol/NaOH protocol
is superior in cases, such as 2j f 7j f 8j, where virtually
quantitative conversion to 8j is observed in <1 h. We
were unable to detect significant amounts of 13j, which
does not mean that this product is not formed during the
isomerization step; however, the isomerization catalyst
working here is obviously so efficient that 7j and 13j
rapidly equilibrate, and 7j is consecutively removed from
the equilibrium by isomerization to 8j.
Finally, a time-conversion curve was recorded for the
triethylsilane protocol (Figure 5). This additive yields an
isomerization catalyst which is intermediate in activity;
the concentration of 7j rapidly decreases with virtually
no induction period. After 13 h, 90% of 7j is converted to
8j and the residual 10% is a 1:1 mixture of 7j and 13j.
The ratio of 8j to 13j appears to be constant over the
reaction time, and it may be concluded that 13j is
probably a “dead end” in this isomerization protocol.
Ta n d em RCM Isom er iza tion P r ocess w ith Eth yl Vin yl
E t h er a s a n Ad d it ive (P r ot ocol c). To a solution of 2c
(0.41 g, 2.0 mmol) in toluene (10 mL) was added [Cl2(PCy3)2-
RudCHPh] (75 mg, 4.6 mol %). The solution was stirred until
the starting material was fully consumed (approximately 20
min, TLC), and ethyl vinyl ether (1.0 mL, 10 mmol) was added.
The mixture was continuously stirred at ambient temperature
(88) Gazzard, L. J .; Motherwell, W. B.; Sandham, D. A. J . Chem.
Soc., Perkin Trans. 1 1999, 979-993.
(89) Shibata, I.; Yoshimura, N.; Yabu, M.; Baba, A. Eur. J . Org.
Chem. 2001, 3207-3211.
Con clu sion
(90) J urd, L.; Roitman, J . N. Tetrahedron 1978, 34, 57-62.
(91) Gravestock, M. B.; Knight, D. W.; Lovell, J . S.; Thornton, S. R.
J . Chem. Soc., Perkin Trans. 1 1999, 3143-3155.
(92) Hartung, J .; Hiller, M.; Schmidt, P. Liebigs Ann. 1996, 1425-
1436.
(93) Schmidt, B. J . Chem. Soc., Perkin Trans. 1 1999, 2627-2637.
(94) Aragone`s, S.; Bravo, F.; D´ıaz, Y.; Matheu, M. I.; Castillo´n, S.
Tetrahedron: Asymmetry 2003, 14, 1847-1856.
(95) Marco, J . A.; Carda, M.; Rodr´ıguez, S.; Castillo, E.; Kneeteman,
M. N. Tetrahedron 2003, 59, 4085-4101.
Olefin isomerization, normally considered to be an
undesired side reaction in olefin metathesis, can be a
synthetically valuable reaction if conditions are found
that allow one to distinguish strictly between metathesis
and isomerization activity. We have developed four
protocols that allow for the use of ruthenium-carbene
complexes in clean isomerization reactions and incorpo-
J . Org. Chem, Vol. 69, No. 22, 2004 7683

Schmidt
for 15 min to allow formation of the intermediate ethoxy-
substituted carbene complex, and the solution was then heated
to reflux until the primarily formed metathesis product was
completely converted to the enol ether (TLC). A color change
from deep red to yellow occured when the solution was heated
to reflux, which indicates the formation of the ruthenium-
hydride species. Evaporation of the solvent and flash chroma-
tography on silica yielded 8c (0.24 g, 67%).
Ta n d em RCM Isom er iza tion P r ocess w ith Na H or
Na BH 4 a s a n Ad d it ive (P r ot ocol d ). To a solution of 2f
(0.98 g, 4.5 mmol) in toluene (30 mL) was added [Cl2(PCy3)2-
RudCHPh] (186 mg, 5.0 mol %). The solution was stirred until
the starting material was fully consumed (approximately 30
min, TLC), and NaH (60% dispersion in mineral oil, 80 mg,
∼2.0 mmol) was added. The solution was then heated to reflux
until the primarily formed metathesis product was completely
converted to the enol ether (TLC). After the reaction mixture
was cooled to ambient temperature, it was diluted with MTBE
and washed with water. The organic layer was separated, dried
with MgSO4, filtered, and evaporated. Flash chromatography
on silica yielded 8f (0.80 g, 94%).
Ta n d em RCM Isom er iza tion P r ocess w ith 2-P r op a n ol
a n d Na OH a s a n Ad d itives (P r otocol e). To a solution of
2f (0.43 g, 2.0 mmol) in toluene (8 mL) was added [Cl2(PCy3)2-
RudCHPh] (82 mg, 5.0 mol %). The solution was stirred until
the starting material was fully consumed (approximately 30
min, TLC), and 2-propanol (2.0 mL) and NaOH (20 mg, 0.5
mmol) were added. The solution was then heated to reflux until
the primarily formed metathesis product was completely
converted to the enol ether (TLC). After the reaction mixture
was cooled to ambient temperature, it was diluted with MTBE
and washed with water. The organic layer was separated, dried
with MgSO4, filtered, and evaporated. Flash chromatography
on silica yielded 8f (0.34 g, 90%).
Ta n d em RCM Isom er iza tion P r ocess w ith Tr ieth ylsi-
la n e a s Ad d itive (P r otocol f). To a solution of 2m (0.27 g,
1.0 mmol) in toluene (10 mL) was added [Cl2(PCy3)2RudCHPh]
(42 mg, 5.0 mol %). The solution was stirred until the starting
material was fully consumed (approximately 30 min, TLC),
and triethylsilane (0.16 mL, 1.0 mmol) was added to the
solution via syringe. The solution was then heated to reflux
until the primarily formed metathesis product was completely
converted to the enol ether (TLC). The solvent was evaporated
and the residue purified by flash chromatography on silica to
give 8m (0.19 g, 79%) as a colorless solid.
An a lytica l Da ta of Cyclic En ol Eth er s 8. 2-(2-Meth -
oxyp h en yl)-2,3-d ih yd r ofu r a n (8a ). P r otocol c. 8a was
obtained from 2a (204 mg, 1.0 mmol) as an 8:1 mixture of
regioisomers. Flash chromatography on silica yields 8a as a
single isomer (136 mg, 77%). P r otocol d . 8a was obtained
from 2a (408 mg, 2.0 mmol) as an 8:1 mixture of regioisomers.
Flash chromatography on silica yields 8a as a single isomer
(280 mg, 79%). P r otocol e. A 3:2:1 mixture of 8a , 10a , and
9a was obtained from 2a (204 mg, 1.0 mmol): 1H NMR (500
MHz, C6D6) δ 2.43 (dddd, J ) 15.2, 8.2, 2.3, 2.3, 1 H), 3.09
(dddd, J ) 15.2, 10.7, 2.3, 2.3, 1 H), 3.25 (s, 3 H), 4.73 (ddd, J
) 2.5, 2.3, 2.3, 1 H), 6.02 (dd, J ) 10.7, 8.2), 6.39 (ddd, J )
2.5, 2.3, 2.3), 6.53 (d, J ) 8.2, 1 H), 6.95 (dd, J ) 7.5, 7.5, 1 H),
7.10 (ddd, J ) 8.2, 7.5, 1.7, 1 H), 7.68 (dd, J ) 7.5, 1.2, 1 H);
13C NMR (125 MHz, C6D6) δ 37.7 (2), 54.8 (3), 78.0 (1), 99.1
(1), 110.4 (1), 120.9 (1), 125.9 (1), 128.3 (1), 132.4 (0), 145.7
(1), 156.1 (0); IR (film, NaCl plates) ν 754 (s), 1051 (s), 1243
(s), 1491 (s), 1621 (s), 2937 (s) cm-1; MS (EI) m/z 176 (100)
[M+], 147 (86), 91 (92). Anal. Calcd for C11H12O2 (176.2): C,
75.0; H, 6.9. Found: C, 74.9; H, 6.7. P r otocol e. A 3:2:1
mixture of 8a , tetrahydrofuran 10a , and the regioisomer of
8a (9a ) was obtained from 2a (204 mg, 1.0 mmol). Tetrahy-
drofuran 10a was identified by comparison with the NMR
spectrum of an authentic sample.61
8b as a single isomer (215 mg, 61%). P r otocol d . 8b was
obtained from 2a (343 mg, 1.7 mmol) as a 3.6:1 mixture of
regioisomers. Flash chromatography on silica yields 8b as a
single isomer (191 mg, 64%): 1H NMR (400 MHz, C6D6) δ 2.43
(dddd, J ) 15.1, 8.5, 2.5, 2.5, 1 H), 2.73 (dddd, J ) 15.1, 10.5,
2.5, 2.5, 1 H), 3.33 (s, 3 H), 4.68 (ddd, J ) 2.5, 2.5, 2.5, 1 H),
5.40 (dd, J ) 10.5, 8.5), 6.31 (ddd, J ) 2.5, 2.5, 2.5), 6.74 (dd,
J ) 7.8, 1.8, 1 H), 6.92 (d, J ) 7.8, 1 H), 7.04 (dd, J ) 1.8, 1.8,
1 H), 7.12 (dd, J ) 7.8, 7.8, 1 H); 13C NMR (100 MHz, C6D6) δ
38.2 (2), 54.7 (3), 82.4 (1), 98.9 (1), 111.4 (1), 113.3 (1), 118.1
(1), 129.8 (1), 145.4 (0), 145.8 (1), 160.4 (0); IR (film, NaCl
plates) ν 697 (s), 783 (s), 1264 (s), 1484 (s), 1586 (s), 1603 (s),
2936 (s) cm-1; MS (EI) m/z 176 (54) [M+], 147 (93), 135 (82),
91 (100). Anal. Calcd for C11H12O2 (176.2): C, 75.0; H, 6.9.
Found: C, 74.9; H, 7.2.
2-P h en eth yl-2,3-d ih yd r ofu r a n (8c). P r otocol c. 8c was
obtained from 2c (405 mg, 2.0 mmol) as a 4:1 mixture of
regioisomers. Flash chromatography on silica yields 8c as a
single isomer (235 mg, 68%). P r otocol d . 8c was obtained
from 2c (500 mg, 2.5 mmol) as a 4.8:1 mixture of regioisomers.
Flash chromatography on silica yields 8c as a single isomer
(305 mg, 70%): 1H NMR (500 MHz, C6D6) δ 1.61 (dddd, J )
13.7, 9.5, 8.2, 5.5, 1 H), 1.92 (dddd, J ) 13.7, 10.0, 6.7, 5.2, 1
H), 1.99 (dddd, J ) 15.0, 7.7, 2.5, 2.5, 1 H), 2.38 (dddd, J )
15.0, 10.2, 2.5, 2.5, 1 H), 2.60 (ddd, J ) 13.8, 9.5, 6.7, 1 H),
2.70 (ddd, J ) 13.8, 9.7, 5.5, 1 H), 4.36 (dddd, J ) 10.2, 8.2,
7.7, 5.2, 1 H), 4.67 (ddd, J ) 2.5, 2.5, 2.5), 6.22 (ddd, J ) 2.5,
2.5, 2.5), 7.07 (d, J ) 7.8, 1 H), 7.15-7.20 (3 H); 13C NMR (125
MHz, C6D6) δ 32.2 (2), 34.9 (2), 38.3 (2), 80.5 (1), 98.7 (1), 126.1
(1), 128.6 (1), 128.8 (1), 142.1 (0), 145.5 (1); IR (film, NaCl
plates) ν 699 (s), 1055 (s), 1140 (s), 1619 (s), 2856 (s), 2930 (s)
cm-1; MS (EI) m/z 174 (25) [M+], 130 (100), 91 (98). Anal. Calcd
for C12H14O (174.3): C, 82.7; H, 8.1. Found: C, 82.7; H, 8.4.
6-(2,3-Dih yd r ofu r a n -2-yl)-3,4-d ih yd r o-2H -p yr a n (8d ).
P r ot ocol c. 8d was obtained from 2d (360 mg, 2.0 mmol)
as a 4:1 mixture of regioisomers. Flash chromatography on
silica yields 8d as a single isomer (210 mg, 69%). P r otocol d .
8d was obtained from 2d (416 mg, 2.3 mmol) as a 2:1 mix-
ture of regioisomers. Flash chromatography on silica yields
8d as a single isomer (175 mg, 53%): 1H NMR (500 MHz,
C6D6) δ 1.37-1.45 (2 H, -OCH2CH2CH2-), 1.70-1.80 (2 H,
-OCH2CH2CH2-), 2.56 (dddd, J ) 15.0, 11.0, 2.5, 2.5, 1 H,
H3), 2.76 (dddd, J ) 15.0, 8.5, 2.5, 2.5, 1 H, H3′), 3.69-3.77 (2
H, -OCH2CH2CH2-), 4.71 (ddd, J ) 2.5, 2.5, 2.5, 1 H, H4),
4.81-4.87 (2 H, -OCdCH-, H2), 6.26 (ddd, J ) 2.5, 2.5, 2.5,
1 H, H5); 13C NMR (125 MHz, C6D6) δ 20.1 (2), 22.6 (2), 33.5
(2), 66.1 (2), 80.8 (1), 96.9 (1), 99.0 (1), 145.7 (1), 153.5 (0); IR
(film, NaCl plates) ν 910 (s), 1052 (s), 1069 (s), 1138 (s), 1621
(s), 1674 (s), 2931 (s) cm-1; MS (EI) m/z 152 (54) [M+], 95 (46),
69 (45), 55 (100). Anal. Calcd for C9H12O2 (152.2): C, 71.0; H,
8.0. Found: C, 70.7; H, 8.3.
1-Oxa sp ir o[4.5]d ec-2-en e (8e). P r otocol c. 8e (225 mg,
74%) was obtained from 2e (360 mg, 2.2 mmol) after flash
chromatography on silica. P r otocol d . 8e (200 mg, 72%) was
obtained from 2e (326 mg, 2.0 mmol) after flash chromatog-
raphy on silica: 1H NMR (400 MHz, C6D6) δ 1.15-1.48 (6 H,
-CH2-), 1.68-1.85 (4 H), 2.20 (dd, J ) 2.3, 2.3, 2 H), 4.65
(dt, J ) 2.5, 2.3, 1 H), 6.22 (dt, J ) 2.5, 2.3, 1 H); 13C NMR
(100 MHz, C6D6) δ 23.2 (2), 25.5 (2), 37.4 (2), 41.1 (2), 86.0 (0),
97.8 (1), 144.7 (1); IR (film, NaCl plates) ν 1062 (s), 1621 (s),
2857 (s), 2933 (s) cm-1; MS (EI) m/z 138 (42) [M+], 81 (100).
Anal. Calcd for C9H14O (138.2): C, 78.2; H, 10.2. Found: C,
78.6; H, 10.0.
2-P h en eth yl-3,4-d ih yd r o-2H-p yr a n (8f). P r otocol a . 8f
(1.06 g, 79%) was obtained from 2f (1.34 g, 7.1 mmol) after
flash chromatography on silica. P r otocol d . 8f (0.80 g, 94%)
was obtained from 2f (0.98 g, 4.5 mmol) after flash chroma-
tography on silica. P r otocol e. 8f (0.27 g, 72%) was obtained
from 2f (0.43 g, 2.0 mmol) after Kugelrohr distillation (0.1
mbar, 120 °C): 1H NMR (400 MHz, C6D6) δ 1.39-1.45 (2 H),
1.58 (dddd, J ) 13.8, 10.8, 7.0, 4.3, 1 H), 1.68-1.92 (3 H), 2.64
(ddd, J ) 13.8, 9.5, 7.0, 1 H), 2.78 (ddd, J ) 13.8, 9.8, 5.3, 1
2-(3-Meth oxyp h en yl)-2,3-d ih yd r ofu r a n (8b). P r otocol
c. 8b was obtained from 2b (408 mg, 2.0 mmol) as a 4:1
mixture of regioisomers. Flash chromatography on silica yields
7684 J . Org. Chem., Vol. 69, No. 22, 2004

Ruthenium-Catalyzed Olefin Isomerization
H), 3.63 (m, 1 H), 4.59 (ddd, J ) 6.3, 5.5, 2.5, 1 H), 6.48 (d, J
) 6.3, 1 H), 7.07-7.22 (5 H); 13C NMR (100 MHz, C6D6) δ 20.1
(2), 28.2 (2), 31.9 (2), 37.5 (2), 74.1 (1), 100.2 (1), 126.1 (1),
128.6 (1), 128.8 (1), 142.4 (0), 144.3 (1); IR (film, NaCl plates)
ν 1066 (s), 1240 (s), 1650 (s), 2924 (s) cm-1; MS (EI) m/z 188
(28) [M+], 91 (100). Anal. Calcd for C13H16O (188.3): C, 82.9;
H, 8.6. Found: C, 82.9; H, 8.4.
2.0, 1 H, H2), 4.08 (dd, J ) 7.2, 6.7, 1 H, PhCH(OC(CH3)2O)-
CH-), 4.50 (m, 1 H, H5), 5.11 (d, J ) 7.2, 1 H, PhCH(OC-
(CH3)2O)CH-), 6.25 (d, J ) 6.0, 1 H, H6), 7.13 (t, J ) 7.5, 1
H, -Ph), 7.22 (dd, J ) 7.5, 7.5, 1 H, -Ph), 7.53 (d, J ) 7.5, 1
H, -Ph); 13C NMR (125 MHz, C6D6) δ 19.3 (3), 24.8 (3), 27.3
(2), 27.4 (2), 76.3 (1), 81.7 (1), 84.1 (1), 100.6 (1), 109.3 (0),
127.0 (1), 127.5 (1), 128.7 (1), 140.3 (0), 143.6 (1). Characteristic
1H NMR data of the minor isomer: 1H NMR (500 MHz,
C6D6) δ 1.37 (ddm, J ) 13.5, 6.3, 1 H, H3′), 1.58 (s, 3 H,
-OC(CH3)2O-), 1.59 (s, 3 H, -OC(CH3)2O-), 2.01 (dddd, J )
13.5, 11.0, 11.0, 6.3, 1 H, H3), 3.68 (ddd, J ) 11.0, 2.0, 2.0, 1
H, H2), 3.77 (dd, J ) 8.5, 2.3, 1 H, PhCH(OC(CH3)2O)CH-),
4.57 (m, 1 H, H5), 5.37 (d, J ) 8.5, 1 H, PhCH(OC(CH3)2O)-
CH-), 6.48 (d, J ) 6.0, 2 H, -Ph), 7.46 (d, J ) 7.5, 2 H, -Ph).
Full 13C NMR data of the minor isomer: 13C NMR (125 MHz,
C6D6) δ 20.2 (3), 25.3 (3), 27.0 (2), 27.5 (2), 71.9 (1), 78.3 (1),
85.5 (1), 100.8 (1), 109.6 (0), 127.0 (1), 127.5 (1), 128.3 (1), 140.3
(0), 144.3 (1); IR (film, NaCl plates) ν 890 (s), 1069 (s), 1242
(s), 1651 (s), 2986 (s) cm-1; MS (EI) m/z 260 (1) [M+], 202 (79),
119 (86), 91 (100). Anal. Calcd for C16H20O3 (260.3): C, 73.8;
H, 7.7. Found: C, 74.6; H, 8.1.
(R)-2-P h en eth yl-3,4-d ih yd r o-2H-p yr a n ((R)-8f). P r oto-
col d . (R)-8f (0.20 g, 71%) was obtained from (R)-2f (0.33 g,
1.5 mmol) after flash chromatography on silica. The enantio-
meric excess of (R)-8f was determined by HPLC analysis
(eluent, 95:5 heptane/2-propanol; flow 1.0 mL min-1, 20 °C)
to be 90% after comparison with that of racemic 8f under
identical conditions: [R]20 +17° (c 1.02, CH2Cl2) for 90% ee.
D
2-Styr yl-3,4-d ih yd r o-2H-p yr a n (8g). P r otocol d . An
inseparable 2.5:1 mixture of 8g and 7g (0.35 g, 90%) was
obtained from 2g (0.45 g, 2.1 mmol) after flash chromatography
on silica. P r otocol e. 8g (0.24 g, 65%) was obtained from 2g
(0.42 g, 2.0 mmol) after flash chromatography on silica,
contaminated with approximately 10% 8f and 10% of another
unidentified byproduct. All attempts to isolate 8g in pure form
failed. NMR data were obtained from the mixture: 1H NMR
(500 MHz, C6D6) δ 1.55-1.70 (2 H, H3,4), 1.75-1.95 (2 H),
4.34 (m, 1 H), 4.63 (m, 1 H), 6.19 (dd, J ) 16.0, 5.7, 1 H), 6.52
(d, J ) 6.2, 1 H), 6.62 (d, J ) 16.0, 1 H), 7.06 (t, J ) 7.5, 1 H),
7.13 (dd, J ) 7.5, 7.5, 2 H), 7.25 (d, J ) 7.5, 2 H); 13C NMR
(125 MHz, C6D6) δ 19.7 (2), 28.6 (2), 75.3 (1), 100.3 (1), 126.8
(1), 127.8 (1), 128.8 (1), 129.6 (1), 130.7 (1), 137.3 (0), 144.1
(1). P r otocol f. A mixture obtained from 2g (0.38 g, 1.7 mmol)
contained, among several other products, 8g. Attempts to
isolate 8g were unsuccessful.
2-P en tyl-3,4-d ih yd r o-2H-p yr a n (8j). P r otocol d . 8j and
7j were obtained from 2j (0.40 g, 2.2 mmol) as an inseparable
5:1 mixture (0.25 g, 74%) after flash chromatography on silica.
P r otocol e. 8j (0.15 g, 70%) was obtained from 2j (0.26 g, 1.4
mmol) after flash chromatography on silica. P r otocol f. 8j
(0.07 g, 72%) was obtained from 2j (0.11 g, 0.6 mmol) after
flash chromatography on silica: 1H NMR (500 MHz, C6D6) δ
0.89 (t, J ) 7.2, 3 H), 1.16-1.68 (10 H), 1.79 (dm, J ) 17.2, 1
H), 1.92 (dm, J ) 17.2, 1 H), 3.67 (m, 1 H), 4.61 (m, 1 H), 6.49
(d, J ) 6.3, 1 H); 13C NMR (125 MHz, C6D6) δ 14.2 (3), 20.3
(2), 23.0 (2), 25.4 (2), 28.2 (2), 32.2 (2), 35.7 (2), 75.1 (1), 100.0
(1), 144.5 (1); IR (film, NaCl plates) ν 1072 (s), 1242 (s), 1650
(s), 2930 (s) cm-1; MS (EI) m/z 154 (32) [M+], 98 (37), 57 (91),
55 (100). Anal. Calcd for C10H18O (154.2): C, 77.9; H, 11.8.
Found: C, 77.9; H, 12.2.
2-(3-P h en yloxir a n yl)-3,4-d ih yd r o-2H-p yr a n (8h ). P r o-
tocol d . An inseparable 3:2 mixture of diastereomers of 8h
(0.12 g, 91%) was obtained from 2h (0.15 g, 0.7 mmol, 3:2
mixture of diastereomers) after flash chromatography on silica.
P r otocol e. An inseparable 3:2 mixture of diastereomers of
8h (0.23 g, 63%) was obtained from 2h (0.42 g, 1.8 mmol, 3:2
mixture of diastereomers) after flash chromatography on silica,
followed by Kugelrohr distillation (0.17 mbar, 150 °C). P r o-
tocol f. An inseparable 3:2 mixture of diastereomers of 8h
(0.08 g, 71%) was obtained from 2h (0.13 g, 0.6 mmol, 3:2
mixture of diastereomers) after flash chromatography on silica.
NMR data of the major isomer: 1H NMR (500 MHz, C6D6) δ
1.55-1.80 (4 H), 2.95 (dd, J ) 5.2, 2.0, 1 H), 3.65 (ddd, J )
9.5, 5.2, 2.7, 1 H), 3.74 (d, J ) 2.0, 1 H), 4.55 (m, 1 H), 6.35
(dm, J ) 6.2, 1 H), 7.05-7.20 (5 H); 13C NMR (125 MHz, C6D6)
δ 10.0 (2), 24.8 (2), 56.9 (1), 63.2 (1), 74.4 (1), 100.8 (1), 125.9
(1), 128.3 (1), 128.7 (1), 137.8 (0), 143.6 (1). Characteristic 1H
NMR data of the minor isomer: 1H NMR (500 MHz, C6D6) δ
2.97 (dd, J ) 5.0, 2.0, 1 H), 3.62 (ddd, J ) 10.2, 5.0, 2.2, 1 H),
3.71 (d, J ) 2.0, 1 H), 4.55 (m, 1 H), 6.42 (dm, J ) 6.2, 1 H).
Full 13C NMR data of the minor isomer: 13C NMR (125 MHz,
C6D6) δ 19.5 (2), 24.6 (2), 54.9 (1), 63.8 (1), 74.6 (1), 100.4 (1),
125.9 (1), 128.3 (1), 128.7 (1), 137.8 (0), 143.9 (1); IR (film, NaCl
2-F u r a n -2-yl-3,4-d ih yd r o-2H-p yr a n (8k ). P r otocol a . 8k
and its regioisomer 9k were obtained from 2k (0.33 g, 2.2
mmol) as an inseparable 1:1 mixture (0.30 g, 91%) after flash
chromatography on silica. Regioisomer 9k was independently
obtained by base-promoted isomerization of 7k . To a solution
of 7k (1.60 g, 10.7 mmol) in DMSO (10 mL) and THF (20 mL)
was added KO-tert-Bu (2.24 g, 20.0 mmol). The mixture was
heated to reflux for 2 h, cooled to ambient temperature, diluted
with MTBE, and washed with brine. The organic layer was
isolated, dried with MgSO4, filtered, and evaporated. The
residue was purified by flash chromatography on silica to give
9k and 8k as an inseparable 4:1 mixture (1.20 g, 75%). NMR
data of 9k : 1H NMR (500 MHz, C6D6) δ 1.46 (m, 2 H), 1.86
(td, J ) 6.5, 4.0, 2 H), 3.80 (m, 2 H), 5.50 (t, J ) 4.0, 1 H), 6.08
(dd, J ) 3.3, 1.7, 1 H), 6.56 (d, J ) 3.5, 1 H), 7.05 (dd, J ) 1.7,
0.8, 1 H); 13C NMR (125 MHz, C6D6) δ 20.2 (2), 22.6 (2), 66.1
(2), 105.4 (1), 111.2 (1), 141.8 (1), 145.6 (1), 151.2 (0). P r otocol
b. 8k (0.29 g, 41%) and tetrahydropyran 10k (0.15 g, 21%)
were obtained from 7k (0.70 g, 4.7 mmol) after flash chroma-
tography on silica. NMR data of tetrahydropyran 10k : 1H
NMR (400 MHz, CDCl3) δ 1.50-1.95 (6 H), 3.57 (ddd, J ) 11.3,
11.3, 2.5, 1 H), 4.03 (dm, J ) 11.3, 1 H), 4.37 (dd, J ) 9.0, 4.3,
1 H), 6.22 (d, J ) 3.3, 1 H), 6.29 (dd, J ) 3.3, 1.8, 1 H), 7.34
(dd, J ) 1.8, 0.8, 1 H); 13C NMR (100 MHz, CDCl3) δ 23.1 (2),
25.6 (2), 29.5 (2), 68.5 (2), 72.9 (1), 106.0 (1), 109.9 (1), 141.9
(1), 155.1 (0). P r otocol d . 8k (0.34 g, 95%) was obtained from
2k (0.40 g, 2.2 mmol) after flash chromatography on silica. A
small amount (<10%) of the regioisomeric dihydropyran 9k
could be observed in the 1H NMR spectrum of the crude
reaction mixture. P r otocol e. 8k (0.36 g, 86%) was obtained
from 2k (0.50 g, 2.8 mmol) after flash chromatography on
silica. P r otocol f. 8k (0.13 g, 83%) was obtained from 2k (0.18
g, 1.0 mmol) after flash chromatography on silica: 1H NMR
(500 MHz, C6D6) δ 1.70-1.87 (3 H), 2.00 (m, 1 H), 4.56 (m, 1
H), 4.76 (dd, J ) 10.2, 2.2, 1 H), 6.09 (dd, J ) 3.0, 0.8, 1 H),
6.18 (d, J ) 3.0, 1 H), 6.43 (d, J ) 6.3, 1 H), 7.10 (d, J ) 0.8,
plates) ν 890 (s), 1068 (s), 1239 (s), 1650 (s), 1925 (m) cm-1
;
MS (EI) m/z 202 (3) [M+], 175 (13), 145 (30), 117 (75), 91 (100).
Anal. Calcd for C13H14O2 (202.3): C, 77.2; H, 7.0. Found: C,
77.1; H, 7.2.
2-(2,2-Dim eth yl-5-ph en yl[1,3]dioxolan -4-yl)-3,4-dih ydr o-
2H-p yr a n (8i). P r otocol d . An inseparable 3:2 mixture of
diastereomers of 8i (0.36 g, 73%) was obtained from 2i (0.58
g, 1.9 mmol, 3:2 mixture of diastereomers) after flash chro-
matography on silica. P r otocol e. An inseparable 3:2 mixture
of diastereomers of 8i (0.36 g, 69%) was obtained from 2i (0.58
g, 2.0 mmol, 3:2 mixture of diastereomers) after flash chro-
matography on silica, followed by Kugelrohr distillation (0.17
mbar, 150 °C). P r otocol f. An inseparable 3:2 mixture of
diastereomers of 8i (0.20 g, 77%) was obtained from 2i (0.29
g, 1.0 mmol, 3:2 mixture of diastereomers) after flash chro-
matography on silica. NMR data of the major isomer: 1H NMR
(500 MHz, C6D6) δ 1.47 (s, 3 H, -OC(CH3)2O-), 1.51 (s, 3 H,
-OC(CH3)2O-), 1.60-1.88 (4 H, H3,4), 3.94 (ddd, J ) 9.7, 6.5,
J . Org. Chem, Vol. 69, No. 22, 2004 7685

Schmidt
1
1 H); 13C NMR (125 MHz, C6D6) δ 19.7 (2), 26.6 (2), 70.6 (1),
100.4 (1), 106.8 (1), 110.4 (1), 142.1 (1), 144.0 (1), 154.9 (0); IR
(film, NaCl plates) ν 1060 (s), 1073 (s), 1238 (s), 1650 (s), 2928
(m) cm-1; MS (EI) m/z 150 (24) [M+], 94 (100). Anal. Calcd for
C9H10O2 (150.2): C, 72.0; H, 6.7. Found: C, 72.1; H, 6.9.
(10o): colorless solid; mp 68 °C; H NMR (500 MHz, C6D6) δ
1.38 (dm, J ) 12.6, 1 H), 1.46 (dddd, J ) 12.6, 12.6, 3.8, 3.8,
1 H), 1.61 (dddd, J ) 12.0, 12.0, 4.3, 4.3, 1 H), 1.68 (dm, J )
12.0, 1 H), 2.05 (ddd, J ) 14.3, 13.1, 3.8, 1 H), 2.20 (dm, J )
14.3, 1 H), 2.27 (s br, 1 H), 3.35 (d, J ) 11.3, 1 H), 3.48 (d, J
) 11.3, 1 H), 3.51 (ddd, J ) 11.8, 11.8, 2.5, 1 H), 3.74 (dm, J
) 11.8, 1 H), 7.22-7.42 (5 H); 13C NMR (100 MHz, C6D6) δ
19.4 (2), 25.9 (2), 28.1 (2), 62.8 (2), 72.0 (2), 79.1 (0), 127.0 (1),
127.2 (1), 128.5 (1), 140.5 (0); IR (film, NaCl plates) ν 1041
(s), 1082 (s), 1446 (s), 2941 (s), 3442 (s) cm-1; MS (EI) m/z [M+]
not observed, 161 (100), 105 (98). Anal. Calcd for C12H16O2
(192.3): C, 75.0; H, 8.4. Found: C, 74.7; H, 8.6.
2-P h en yl-3,4-d ih yd r o-2H-p yr a n (8l). P r otocol d . 8l (0.28
g, 87%) was obtained from 2l (0.38 g, 2.0 mmol) after flash
chromatography on silica. P r otocol e. 8l (0.25 g, 82%) was
obtained from 2l (0.35 g, 1.9 mmol) after flash chromatography
on silica: 1H NMR (400 MHz, C6D6) δ 1.70-1.80 (3 H), 1.94
(m, 1 H), 4.64 (m, 1 H), 4.70 (dd, J ) 8.0, 4.5, 1 H), 6.57 (d, J
) 5.8, 1 H), 7.11 (t, J ) 7.3, 1 H), 7.19 (dd, J ) 7.3, 7.3, 2 H),
7.29 (d, J ) 7.3, 2 H); 13C NMR (100 MHz, C6D6) δ 20.2 (2),
30.4 (2), 76.8 (1), 100.2 (1), 125.8 (1), 127.3 (1), 128.2 (1), 142.4
(0), 144.3 (1); IR (film, NaCl plates) ν 1059 (s), 1076 (s), 1241
(s), 1650 (s), 2847 (s), 2922 (s), 3060 (s) cm-1; MS (EI) m/z 160
2-Meth oxym eth yl-2-p h en yl-3,4-d ih yd r o-2H-p yr a n (8p ).
P r otocol d . 8p (0.30 g, 80%) was obtained from 2p (0.45 g,
1.9 mmol) after flash chromatography on silica. P r otocol e.
8p (0.31 g, 76%) was obtained from 2p (0.46 g, 2.0 mmol) after
flash chromatography on silica, followed by Kugelrohr distil-
lation (0.15 mbar, 150 °C). P r otocol f. 8p (0.09 g, 74%) was
obtained from 2p (0.13 g, 0.6 mmol) after flash chromatogra-
phy on silica: 1H NMR (400 MHz, C6D6) δ 1.62 (ddm, J ) 17.2,
10.5, 1 H), 1.74 (dm, J ) 17.2, 1 H), 2.09 (ddd, J ) 13.7, 4.7,
4.5, 1 H), 2.25 (ddd, J ) 13.7, 10.5, 5.5, 1 H), 3.08 (s, 3 H),
3.39 (d, J ) 10.0, 1 H), 3.48 (d, J ) 10.0, 1 H), 4.52 (m, 1 H),
6.49 (d, J ) 6.2, 1 H), 7.12 (t, J ) 7.5, 1 H), 7.22 (dd, J ) 7.5,
7.5, 2 H), 7.46 (d, J ) 7.5, 2 H); 13C NMR (100 MHz, C6D6) δ
17.5 (2), 27.8 (2), 59.2 (3), 79.7 (2), 80.3 (0), 100.8 (1), 126.2
(1), 127.3 (1), 128.3 (1), 142.7 (1), 142.9 (0); IR (film, NaCl
(16) [M+], 131 (23), 104 (100). Anal. Calcd for C11H12
(160.2): C, 82.5; H, 7.6. Found: C, 82.1; H, 7.7.
O
2-(2-Met h oxyn a p h t h a len -1-yl)-3,4-d ih yd r o-2H -p yr a n
(8m ). P r otocol d. A crude reaction mixture was obtained (0.23
g, 100%) from 2m (0.27 g, 1.0 mmol) after 10 h in refluxing
toluene, which contains 8m , 7m , and its isomer 13m in a 10:
4:1 ratio. P r otocol e. 8m (0.46 g, 80%) was obtained from 2m
(0.65 g, 2.4 mmol) after flash chromatography as a viscous oil,
which solidifies upon standing at 0 °C. Mp 93 °C. P r otocol f.
8m (0.19 g, 79%) was obtained from 2m (0.27 g, 1.0 mmol)
after flash chromatography: 1H NMR (500 MHz, C6D6) δ 1.82-
1.93 (2 H), 2.24 (m, 1 H), 2.67 (ddd, J ) 12.0, 12.0, 5.7, 1 H),
3.33 (s, 3 H), 4.77 (m, 1 H), 6.17 (dd, J ) 12.0, 1.8, 1 H), 6.68
(d, J ) 6.2, 1 H), 6.86 (d, J ) 9.0, 1 H), 7.23 (dd, J ) 7.7, 7.2,
1 H), 7.38 (dd, J ) 8.2, 7.2, 1 H), 7.57 (d, J ) 9.0, 1 H), 7.68
(d, J ) 8.2, 1 H), 8.71 (d, J ) 8.7, 1 H); 13C NMR (125 MHz,
C6D6) δ 21.4 (2), 28.0 (2), 56.1 (3), 72.4 (1), 100.8 (1), 113.3 (1),
122.8 (0), 123.7 (1), 126.2 (1), 126.3 (1), 128.8 (1), 130.1 (1),
130.4 (0), 133.2 (0), 144.8 (1), 154.3 (0); IR (film, NaCl plates)
plates) ν 1065 (s), 1109 (s), 1246 (s), 1652 (s), 2924 (s) cm-1
;
MS (EI) m/z 204 (10) [M+], 159 (100). Anal. Calcd for C13H16O2
(204.3): C, 76.4; H, 7.9. Found: C, 76.9; H, 7.9.
(2R*,3R*)-2-P h en yl-3,4-dih ydr o-2H-pyr an -3-ol (8q). P r o-
tocol e. 8q (0.12 g, 40%) was obtained from 2q (0.34 g, 1.7
mmol) after flash chromatography on silica. The isomerization
step must be carefully monitored by TLC and stopped when
tetrahydropyran 10q is detected. Following the same protocol,
we obtained tetrahydropyran 10q (0.13 g, 46%) from 2q (0.32
g, 1.6 mmol) by heating the reaction mixture until 8q was
completely consumed. Analytical data for 8q: 1H NMR (400
MHz, C6D6) δ 1.59 (s br, 1 H), 1.90 (dm, J ) 17.3, 1 H), 2.07
(dm, J ) 17.3, 1 H), 3.78 (s br, 1 H), 4.49 (m, 1 H), 4.56 (s br,
1 H), 6.43 (d, J ) 6.0, 1 H), 7.12 (t, J ) 7.5, 1 H), 7.20 (dd, J
) 7.5, 7.5, 2 H), 7.33 (d, J ) 7.5, 2 H); 13C NMR (100 MHz,
C6D6) δ 29.4 (2), 66.9 (1), 78.4 (1), 98.1 (1), 126.7 (1), 127.8 (1),
128.4 (1), 139.3 (0), 144.0 (1); IR (film, NaCl plates) ν 701 (s),
ν 808 (s), 1051 (s), 1076 (s), 1242 (s), 1252 (s), 1649 (s) cm-1
;
MS (EI) m/z 240 (30) [M+], 184 (100). Anal. Calcd for C16H16O2
(240.3): C, 80.0; H, 6.7. Found: C, 79.9; H 6.9.
2-P h en yl-3,4-dih ydr o-2H-pyr an -2-car boxylic Acid Meth -
yl Ester (8n ). P r otocol e. 8n (0.32 g, 70%) was obtained from
2n (0.52 g, 2.1 mmol) after flash chromatography on silica,
followed by Kugelrohr distillation (0.25 mbar, 150 °C): 1H
NMR (500 MHz, C6D6) δ 1.70 (dm, J ) 17.2, 1 H), 1.99 (ddd,
J ) 13.2, 9.7, 5.7, 1 H), 2.09 (m, 1 H), 2.65 (ddd, J ) 13.0, 5.0,
4.5, 1 H), 3.23 (s, 3 H), 4.61 (m, 1 H), 6.56 (d, J ) 6.2, 1 H),
7.07 (t, J ) 7.5, 1 H), 7.18 (dd, J ) 7.5, 7.5, 2 H), 7.72 (d, J )
7.5, 2 H); 13C NMR (100 MHz, C6D6) δ 18.2 (2), 31.1 (2), 52.0
(3), 81.1 (0), 101.4 (1), 125.5 (1), 128.2 (1), 128.6 (1), 140.7 (1),
143.1 (0), 172.5 (0); IR (film, NaCl plates) ν 1073 (s), 1231 (s),
1274 (s), 1654 (s), 1732 (s), 1753 (s), 3062 (m) cm-1; MS (EI)
m/z 218 (30) [M+], 159 (100), 103 (85). Anal. Calcd for C13H14O3
(218.3): C, 71.5; H, 6.5. Found: C, 71.6; H, 6.8.
(2-P h en yl-3,4-d ih yd r o-2H -p yr a n -2-yl)m et h a n ol (8o).
P r otocol d . No amount of 8o was obtained from 2o (0.45 g,
2.1 mmol), but 7o was exclusively obtained as the primary
metathesis product43 (0.36 g, 90%). P r otocol e. 8o (0.23 g,
48%) and 10o (0.05 g, 10%) were obtained from 2o (0.55 g, 2.5
mmol) after chromatography on silica. 8o was further purified
by Kugelrohr distillation (0.25 mbar, 150 °C) and thus obtained
as a colorless solid. Mp 72 °C. Analytical data for 8o: 1H NMR
(500 MHz, C6D6) δ 1.55 (ddddd, J ) 17.2, 11.5, 5.7, 2.2, 2.2, 1
H), 1.65 (dm, J ) 17.2, 1 H), 1.76 (s br, 1 H), 1.91 (dd, J )
13.7, 4.5, 1 H), 2.14 (ddd, J ) 13.7, 11.5, 5.7, 1 H), 3.50 (dd, J
) 11.5, 8.0, 1 H), 3.60 (dd, J ) 11.5, 2.0, 1 H), 4.50 (m, 1 H),
6.42 (d, J ) 6.2, 1 H), 7.09 (t, J ) 7.2, 1 H), 7.18 (dd, J ) 7.7,
7.2, 2 H), 7.26 (d, J ) 7.7, 2 H); 13C NMR (100 MHz, C6D6) δ
17.4 (2), 27.0 (2), 70.4 (2), 81.0 (0), 101.3 (1), 125.9 (1), 127.3
(1), 128.5 (1), 142.0 (0), 142.5 (1); IR (film, NaCl plates) ν 696
(s), 757 (s), 1055 (s), 1080 (s), 1241 (s), 1447 (s), 1651 (s), 3261
(s) cm-1; MS (EI) m/z 190 (10) [M+], 159 (100). Anal. Calcd for
734 (s), 1071 (s), 1239 (s), 1652 (s), 2923 (s), 3416 (s) cm-1
MS (EI) m/z 176 (6) [M+], 120 (100), 91 (77). Anal. Calcd for
11H12O2 (176.2): C, 75.0; H, 6.9. Found: C, 75.0; H, 7.3.
;
C
Analytical data for (2R*,3R*)-2-phenyltetrahydropyran-3-ol
(10q): 1H NMR (500 MHz, CDCl3) δ 1.47 (m, 1 H), 1.72 (s br,
1 H), 1.88 (m, 1 H), 2.05-2.15 (2 H), 3.65 (ddd, J ) 12.2, 10.5,
2.0, 1 H), 3.92 (s br, 1 H), 4.19 (dd, J ) 10.5, 3.0, 1 H), 4.50 (s
br, 1 H), 7.20-7.45 (5 H); 13C NMR (125 MHz, CDCl3) δ 19.8
(2), 30.1 (2), 67.9 (1), 68.9 (2), 81.1 (1), 125.7 (1), 127.4 (1),
128.4 (1), 139.5 (0); IR (film, NaCl plates) ν 731 (s), 1091 (s),
1451 (s), 2927 (s), 3432 (s) cm-1; MS (EI) m/z 178 (39) [M+],
107 (100), 79 (61).
(2R*,3R*)-ter t-Bu tyld im eth yl(2-ph en yl-3,4-dih yd r o-2H-
p yr a n -3-yloxy)sila n e (8r ). P r otocol d . 8r (0.20 g, 87%) was
obtained from 2r (0.25 g, 0.8 mmol) after flash chromatography
on silica. P r otocol e. 8r (0.27 g, 84%) was obtained from 2r
(0.36 g, 1.1 mmol) after flash chromatography on silica: 1H
NMR (400 MHz, C6D6) δ -0.40 (s, 3 H, -Si(CH3)2), -0.18 (s,
3 H, -Si(CH3)2), 0.88 (s, 9 H, -C(CH3)3), 1.90 (dm, J ) 17.0,
1 H, H4), 2.17 (dm, J ) 17.0, 1 H, H4′), 3.87 (s br, 1 H, H3),
4.55 (m, 1 H, H5), 4.70 (s br, 1 H, H2), 6.56 (d, J ) 6.0, 1 H,
H6), 7.12 (t, J ) 7.5, 1 H, -Ph), 7.22 (dd, J ) 7.5, 7.5, 2 H,
-Ph), 7.41 (d, J ) 7.5, 2 H, -Ph); 13C NMR (100 MHz, C6D6)
δ -5.4 (3), -5.1 (3), 18.2 (0), 25.9 (3), 29.8 (2), 68.3 (1), 78.9
(1), 97.2 (1), 127.2 (1), 127.5 (1), 127.8 (1), 139.1 (0), 144.1 (1);
IR (film, NaCl plates) ν 836 (s), 1074 (s), 1103 (s), 1241 (s),
1657 (s), 2856 (s), 2928 (s), 2955 (s) cm-1; MS (EI) m/z [M+]
C
12H14O2 (190.2): C, 75.8; H, 7.4. Found: C, 75.7; H, 7.4.
Analytical data for (2-phenyltetrahydropyran-2-yl)methanol
7686 J . Org. Chem., Vol. 69, No. 22, 2004

Ruthenium-Catalyzed Olefin Isomerization
not observed, 233 (90), 177 (90), 91 (100). Anal. Calcd for
m/z 204 (48) [M+], 147 (100). Anal. Calcd for C13H16O2 (204.3):
C, 76.4; H, 7.9. Found: C, 76.5; H, 8.0.
C
17H26O2Si (290.5): C, 70.3; H, 9.0. Found: C, 70.5; H, 9.1.
3-Eth yl-2-p h en yl-3,4-d ih yd r o-2H-p yr a n -3-ol (8s). P r o-
(2R*,3R*)-ter t-Bu tyld im eth yl(2-p h en yl-2,3,4,5-tetr a h y-
d r ooxep in -3-yloxy)sila n e (8w ). P r otocol d . 8w (0.18 g,
82%) was obtained from 2w (0.22 g, 0.7 mmol) after flash
chromatography on silica. P r otocol e. 8w (0.18 g, 74%) was
obtained from 2w (0.26 g, 0.8 mmol) after flash chromatog-
raphy on silica: 1H NMR (500 MHz, C6D6) δ -0.49 (s, 3 H,
-Si(CH3)2), -0.21 (s, 3 H, -Si(CH3)2), 0.86 (s, 9 H, -C(CH3)3),
1.81 (dddd, J ) 13.5, 8.5, 5.7, 2.0, 1 H, H4), 2.00 (ddm, J )
16.7, 10.5, 1 H, H3), 2.09 (m, 1 H, H3′), 2.12 (dddd, J ) 13.5,
10.2, 7.7, 2.5, 1 H, H4′), 3.91 (ddd, J ) 7.5, 5.5, 2.0, 1 H, H3),
4.68 (ddd, J ) 6.2, 6.2, 4.2, 1 H, H6), 4.91 (s br, 1 H, H2), 6.46
(dd, J ) 6.2, 1 H, H7), 7.10 (t, J ) 7.5, 1 H, -Ph), 7.20 (dd, J
) 7.5, 7.5, 1 H, -Ph), 7.35 (d, J ) 7.5, 1 H, -Ph); 13C NMR
(125 MHz, C6D6) δ -5.6 (3), -4.8 (3), 18.2 (2), 21.7 (0), 26.0
(3), 35.5 (2), 75.7 (1), 86.7 (1), 108.9 (1), 127.2 (1), 127.9 (1),
128.1 (1), 140.7 (0), 149.0 (1); IR (film, NaCl plates) ν 836 (s),
1099 (s), 1254 (s), 1649 (s), 2929 (s), 2952 (s) cm-1; MS (EI)
m/z [M+] not observed, 247 (75), 191 (100), 155 (75). Anal.
Calcd for C18H28O2Si (304.5): C, 71.0; H, 9.3. Found: C, 71.4;
H, 9.3.
Tr ieth yl(2-p h en yl-3,4-d ih yd r o-2H-p yr a n -2-ylm eth oxy)-
sila n e (8x). P r otocol f. 8x (0.51 g, 84%) was obtained from
2o (0.44 g, 2.0 mmol) after Kugelrohr distillation (0.30 mbar,
175 °C). When the reaction was monitored by TLC [hexane/
MTBE, 10:1 (v/v)], it was revealed that after addition of
triethylsilane and after the mixture had been heated to reflux
within 1 h silylation of the hydroxy group occurs and then
(within 8 h) isomerization to 8x: 1H NMR (500 MHz, C6D6) δ
0.52-0.60 (6 H), 0.96 (t, J ) 8.0, 9 H), 1.65 (ddm, J ) 17.0,
11.2, 1 H), 1.76 (dm, J ) 17.0, 1 H), 2.15 (dm, J ) 13.7, 1 H),
2.26 (ddd, J ) 13.7, 11.2, 5.7, 1 H), 3.69 (d, J ) 10.5, 1 H),
3.82 (d, J ) 10.5, 1 H), 4.53 (m, 1 H), 6.49 (d, J ) 6.0, 1 H),
7.12 (t, J ) 7.5, 1 H), 7.22 (dd, J ) 7.5, 7.5, 2 H), 7.45 (d, J )
7.5, 2 H); 13C NMR (100 MHz, C6D6) δ 4.8 (2), 7.0 (3), 17.6 (2),
27.2 (2), 70.8 (2), 80.6 (0), 100.9 (1), 126.3 (1), 127.3 (1), 128.3
(1), 142.7 (0), 142.8 (1); IR (film, NaCl plates) ν 698 (s), 727
(s), 1066 (s), 1121 (s), 1246 (s), 1652 (s), 2876 (s), 2913 (s), 2954
(s) cm-1; MS (EI) m/z 304 (2) [M+], 275 (20), 219 (30), 159 (100).
Anal. Calcd for C18H28O2Si (304.5): C, 71.0; H, 9.3. Found: C,
71.3; H, 9.5.
tocol d . No 8s was obtained from 2s (0.23 g, 1.0 mmol), but
7s was obtained exclusively as the primary metathesis prod-
uct45 (0.17 g, 84%). P r otocol e. 8s (0.27 g, 66%) was obtained
from 2s (0.46 g, 2.0 mmol) as a 4:1 mixture of diastereoisomers
after flash chromatography on silica. A higher catalyst loading
(131 mg, 8 mol % [RuCl2(PCy3)2dCHPh]) was required for
this example. NMR data of the major isomer: 1H NMR (600
MHz, C6D6) δ 0.75 (t, J ) 7.3, 1 H, -CH3), 1.00 (dq, J ) 13.9,
7.3, 1 H, -CH2CH3), 1.18 (dq, J ) 13.9, 7.3, 1 H, -CH2CH3),
1.82 (dd, J ) 17.2, 4.8, 1 H, H4), 1.90 (dm, J ) 17.2, 1 H,
-CH2CH3), 4.37 (s, 1 H, H2), 4.54 (ddd, J ) 5.9, 4.8, 2.6, 1 H,
H5), 6.44 (d, J ) 5.9, 1 H, H6), 7.10-7.21 (3 H, -Ph), 7.39 (d,
J ) 7.5, 2 H, -Ph); 13C NMR (150 MHz, C6D6) δ 6.7 (3), 30.6
(2), 32.6 (2), 69.7 (0), 83.3 (1), 98.8 (1), 128.0 (1), 128.2 (1),
128.9 (1), 137.6 (0), 144.1 (1). NMR data of the minor isomer:
1H NMR (600 MHz, C6D6) δ 0.74 (t, J ) 7.5, 1 H, -CH3), 1.10
(dq, J ) 14.3, 7.5, 1 H, -CH2CH3), 1.50 (dq, J ) 14.3, 7.5, 1
H, -CH2CH3), 2.01 (d, J ) 16.9, 1 H, H4), 2.09 (dd, J ) 16.9,
3.3, 1 H, -CH2CH3), 4.51 (m, 1 H, H5), 4.79 (s, 1 H, H2), 6.38
(d, J ) 6.2, 1 H, H6), 7.10-7.21 (3 H, -Ph), 7.41 (d, J ) 7.3,
2 H, -Ph); 13C NMR (150 MHz, C6D6) δ 6.7 (3), 25.7 (2), 30.4
(2), 70.0 (0), 84.5 (1), 98.8 (1), 128.0 (1), 128.1 (1), 128.3 (1),
138.1 (0), 143.5 (1); IR (film, NaCl plates) ν 1071 (s), 1240 (s),
1652 (s), 2939 (s), 2970 (s), 3536 (s) cm-1; MS (EI) m/z 204 (4)
[M+], 148 (30), 98 (100). Anal. Calcd for C13H16O2 (204.3): C,
76.4; H, 7.9. Found: C, 76.4; H, 8.0.
2-Ben zyloxym eth yl-3,4-d ih yd r o-2H-p yr a n (8t). P r oto-
col d . 8t (0.18 g, 87%) was obtained from 2t (0.23 g, 1.0 mmol)
after Kugelrohr distillation (0.2 mbar, 150 °C). P r otocol e.
8t (0.39 g, 91%) was obtained from 2t (0.49 g, 2.1 mmol) after
Kugelrohr distillation (0.2 mbar, 150 °C): 1H NMR (500 MHz,
C6D6) δ 1.58-1.65 (2 H), 1.73 (m, 1 H), 1.85 (m, 1 H), 3.38 (dd,
J ) 10.0, 5.2, 1 H), 3.51 (dd, J ) 10.0, 5.5, 1 H), 3.96 (m, 1 H),
4.36 (s, 2 H), 4.56 (m, 1 H), 6.44 (d, J ) 6.2, 1 H), 7.11 (t, J )
7.5, 1 H), 7.18 (dd, J ) 7.5, 7.5, 2 H), 7.29 (d, J ) 7.5, 2 H); 13
C
NMR (125 MHz, C6D6) δ 19.6 (2), 25.0 (2), 72.7 (2), 73.4 (2),
74.4 (1), 100.3 (1), 127.6 (1), 128.5 (1), 139.1 (0), 144.1 (1); IR
(film, NaCl plates) ν 698 (s), 734 (s), 1071 (s), 1100 (s), 1241
(s), 1650 (s), 2853 (s), 2922 (s), 3061 (s) cm-1; MS (EI) m/z 204
(6) [M+], 113 (58), 91 (100). Anal. Calcd for C13H16O2 (204.3):
C, 76.4; H, 7.9. Found: C, 76.7; H, 8.3.
Ack n ow led gm en t. This work was generously sup-
ported by the Deutsche Forschungsgemeinschaft and
the Chemistry Department of the University of Dort-
mund.
2-(4-Met h oxyp h en yl)-2,3,4,5-t et r a h yd r ooxep in e (8u ).
P r otocol d . 8u (0.09 g, 44%) was obtained from 2u (0.23 g,
1.0 mmol) after flash chromatography on silica. P r otocol e.
8u (0.21 g, 51%) was obtained from 2u (0.47 g, 2.0 mmol) after
flash chromatography on silica: 1H NMR (500 MHz, C6D6) δ
1.39 (m, 1 H), 1.78-2.01 (4 H), 2.11 (m, 1 H), 3.33 (s, 3 H),
4.72-4.78 (2 H), 6.50 (dd, J ) 7.0, 1.0, 1 H), 6.82 (d, J ) 8.5,
1 H), 7.28 (d, J ) 8.5, 1 H); 13C NMR (125 MHz, C6D6) δ 26.1
(2), 26.2 (2), 39.4 (2), 54.7 (3), 84.2 (1), 109.7 (1), 113.9 (1),
127.3 (1), 136.1 (0), 148.0 (1), 159.4 (0); IR (film, NaCl plates)
ν 1248 (s), 1514 (s), 1613 (s), 1649 (s), 2930 (s) cm-1; MS (EI)
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures and analytical data for compounds 1, 2, and 7.
Experimental procedures and analytical data for the control
experiments. This material is available free of charge via the
Internet at http://pubs.acs.org.
J O048937W
J . Org. Chem, Vol. 69, No. 22, 2004 7687