Chromenes through metal-catalyzed reactions of styrenyl ethers. Mechanism and utility in synthesis

Article abstract of DOI:10.1021/ja9739796

An efficient metal-catalyzed process that converts styrenyl ethers to 2-substituted chromenes is described. This class of reactions may be carried out on either terminal or disubstituted styrenyl substrates. Depending on the level of substitution of the olefins, the Ru-carbene catalyst may initiate reaction either by interaction with the styrenyl or the carbocyclic alkene. Metal-catalyzed rearrangements, carried out under an atmosphere of ethylene, afford excellent yields of monomeric products. With disubstituted styrene ethers, the presence of ethylene is also critical to reaction efficiency. Mechanistic data that rationalize these observations are provided. Although Ru complexes (PCy₃)₂Cl₂Ru=CHCH=CPh₂ or (PCy₃)₂Cl₂Ru=CHPh effectively serve as catalysts, with the more functionalized substrates, higher yields are obtained when Mo(CHCMe₂Ph)(N(2,6-(i-Pr)₂C₆H₃))(OCMe(CF₃)₂)₂ is used. A variety of starting materials for the metal-catalyzed chromene synthesis (disubstituted styrenes) are available in the optically pure form through the Zr-catalyzed kinetic resolution protocol, allowing several 2-substituted chromenes to be prepared in high enantiomeric purity. However, a number of functionalized substrates cannot be efficiently resolved by the latter method, indicating that more effective methods that address this deficiency are required.

Full text of DOI:10.1021/ja9739796

J. Am. Chem. Soc. 1998, 120, 2343-2351
2343
Chromenes through Metal-Catalyzed Reactions of Styrenyl Ethers.
Mechanism and Utility in Synthesis
Joseph P. A. Harrity,† Daniel S. La, Dustin R. Cefalo, Michael S. Visser, and
Amir H. Hoveyda*
Contribution from the Department of Chemistry, Merkert Chemistry Center, Boston College,
Chestnut Hill, Massachusetts 02167
ReceiVed NoVember 20, 1997
Abstract: An efficient metal-catalyzed process that converts styrenyl ethers to 2-substituted chromenes is
described. This class of reactions may be carried out on either terminal or disubstituted styrenyl substrates.
Depending on the level of substitution of the olefins, the Ru-carbene catalyst may initiate reaction either by
interaction with the styrenyl or the carbocyclic alkene. Metal-catalyzed rearrangements, carried out under an
atmosphere of ethylene, afford excellent yields of monomeric products. With disubstituted styrene ethers, the
presence of ethylene is also critical to reaction efficiency. Mechanistic data that rationalize these observations
are provided. Although Ru complexes (PCy3)2Cl2RudCHCHdCPh2 or (PCy3)2Cl2RudCHPh effectively serve
as catalysts, with the more functionalized substrates, higher yields are obtained when Mo(CHCMe2Ph)(N(2,6-
(i-Pr)2C6H3))(OCMe(CF3)2)2 is used. A variety of starting materials for the metal-catalyzed chromene synthesis
(disubstituted styrenes) are available in the optically pure form through the Zr-catalyzed kinetic resolution
protocol, allowing several 2-substituted chromenes to be prepared in high enantiomeric purity. However, a
number of functionalized substrates cannot be efficiently resolved by the latter method, indicating that more
effective methods that address this deficiency are required.
Introduction and Background
stituted chromenes 10, 12, and 14 are appreciably lower in
energy than ethers 9, 11, and 13. Several investigations have
demonstrated that various metal-catalyzed metathesis reactions5
are governed by thermodynamic factors;6 this issue is particu-
larly critical in rearrangements, where products can revert back
to starting substrates.7 Our preliminary observations indicated
that the reactivity of the cycloheptenyl substrates (e.g., 1 or 5)
is consistent with the aforementioned energetics. We were,
however, intrigued by the sluggish reactions of six-membered
ring system 11 and the fact that <2% reaction occurs when
cyclopentenyl ether 9 is used. We reasoned that a step in the
catalytic cycle likely serves as a kinetic barrier to the formation
of chromenes 10 and 12.
In this article, we report our investigations in connection with
the mechanism of this metal-catalyzed chromene synthesis
involving terminal and disubstituted styrenyl substrates. We
demonstrate that a mechanistic divergence arises as a result of
subtle structural modifications. From the outset, as depicted
in Chart 1, our plan has been to synthesize optically pure ether
substrates through the Zr-catalyzed kinetic resolution,8 followed
by a metal-catalyzed conversion to the derived nonracemic
We recently reported a two-step, fully catalytic process for
the enantioselective synthesis of 2-substituted chromenes.1,2 As
the examples in Scheme 1 illustrate, we demonstrated that
treatment of a styrenyl ether, such as 1, with 5 mol % (PCy3)2-
Cl2RudCHCHdCPh2 (2)3 under an atmosphere of argon (14
h) leads to the formation of 3 and 4 in 42% and 41% yield,
respectively, after silica gel chromatography. When the reaction
is performed under an atmosphere of ethylene, 3 is obtained in
91% isolated yield. Furthermore, as exemplified by conversion
of 5 to 6, the electronic properties of the aromatic moieties
exhibit little influence on the facility of the catalytic heterocycle
synthesis. Eight-membered rings are appropriate substrates as
well (Scheme 1; 7 f 8).
We conjectured that the above catalytic processes would be
efficient on the basis of two principles: (1) We were mindful
of studies of Crowe4 that aromatic alkenes and aliphatic olefins
are electronically suitable to undergo cross-metathesis. We
envisioned that the intramolecular variant should be especially
favored. (2) The general reaction appeared energetically
favorable: as shown in Scheme 2, initial semiempirical calcula-
tions (PM3; geometry optimization) indicated that the 2-sub-
(5) (a) Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1995, 28,
446-452. (b) Schmalz, H.-G. Angew. Chem., Int. Ed. Engl. 1995, 34, 1833-
1836. (c) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997,
36, 2036-2056.
(6) (a) Miller, S. J.; Kim, S.; Chen, Z.; Grubbs, R. H. J. Am. Chem. Soc.
1995, 117, 2108-2109. (b) Marsella, M. J.; Maynard, H. D.; Grubbs, R.
H. Angew. Chem., Int. Ed. Engl. 1997, 36, 1101-1103 and references
therein.
(7) Catalytic transformations of both terminal and disubstituted styrenyl
ethers will be discussed in this article. In the former case, since the starting
material and the product are isomeric, the Ru-catalyzed process constitutes
a rearrangement.
(8) Visser, M. S.; Harrity, J. P. A.; Hoveyda, A. H. J. Am. Chem. Soc.
1996, 118, 3779-3780. For a recent review, see: Hoveyda, A. H.; Morken,
J. P. Angew. Chem., Int. Ed. Engl. 1996, 35, 1262-1284.
† Present address: Department of Chemistry, University of Sheffield,
Sheffield S3 7HF, United Kingdom.
(1) Harrity, J. P. A.; Visser, M. S.; Gleason, J. D.; Hoveyda, A. H. J.
Am. Chem. Soc. 1997, 119, 1488-1489.
(2) For Mn-catalyzed kinetic resolution of 2,2-disubstituted chromenes,
see: Vander Velde, S. L.; Jacobsen, E. N. J. Org. Chem. 1995, 60, 5380-
5381.
(3) Wu, Z.; Nguyen, S. T.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem.
Soc. 1995, 117, 5503-5511.
(4) (a) Crowe, W. E.; Zhang, Z. J. J. Am. Chem. Soc. 1993, 115, 10998-
10999. (b) Crowe, W. E.; Goldberg, D. R. J. Am. Chem. Soc. 1995, 117,
5162-5163. (c) Crowe, W. E.; Goldberg, D. R.; Zhang, Z. J. Tetrahedron
Lett. 1996, 37, 2117-2120.
S0002-7863(97)03979-6 CCC: $15.00 © 1998 American Chemical Society
Published on Web 03/03/1998

2344 J. Am. Chem. Soc., Vol. 120, No. 10, 1998
Harrity et al.
Scheme 1
Scheme 2
reasons. (2) Involvement of a tetracyclic intermediate such as
16 provides a plausible rationale for the reluctance of six-
membered ring ethers to participate in the catalytic rearrange-
ment and for the lack of reactivity of cyclopentenyl substrates.
The attendant angle strain inhibits the formation of the derived
tetracyclic intermediate. (3) Reactions under ethylene atmo-
sphere inhibit dimer formation, since 17 is intercepted with H2-
CCH2, rather than 14. Furthermore, we find that treatment of
18 with 5 mol % 2 under an atmposphere of ethylene leads to
1
50% conversion to 14 (12 h; 400 MHz H NMR analysis).
Therefore, in the presence of ethylene, even if dimer is formed,
it can be readily converted to the monomeric form with
reasonable efficiency.
To ascertain whether the Ru-catalyzed reaction of the terminal
styrene involves initial reaction at the cyclic alkene, the
following experiments were carried out. As illustrated in eq 1,
chromene. We provide data indicating that with the more
functionalized starting materials, catalytic resolution can be
effective, but chromene synthesis requires the use of an
alternative metathesis catalyst (in lieu of 2 or related Ru
complexes).
Chart 1
when styrenyl ether 19 and allylic phenyl ether 20 are treated
1
with 5 mol % 2, <2% conversion is detected by 400 MHz H
Results and Discussion
NMR analysis after 16 h. In contrast, when 20 is alone
subjected to the above conditions (styrene 19 excluded), facile
ring opening occurs and 1H NMR analysis indicates the
formation of oligomeric products.10 Identical results are
obtained with the more active (PCy3)2Cl2RudC(H)Ph (21).11
Thus, the intermolecular variant (cross-metathesis)12 of the title
reaction (19 + 20) is extremely slow. These data also suggest
Regioselectivity in the Ru-Catalyzed Reactions of Termi-
nal Styrenes. Initially, we surmised that with terminal styrenes
such as 13, reaction begins regioselectively with the formation
of metal-carbene 15 (Scheme 3).9 Subsequent rearrangement,
via metallacyclobutane 16, affords chromene 17, reaction of
which with a second equivalent of 13 would regenerate 15 to
deliver 14. Late in the process (under Ar atm), as the amount
of 14 increases, 17 may react more frequently with the final
product monomer (14) to afford dimer 18.
(10) Hillmyer, M. A.; Laredo, W. R.; Grubbs, R. H. Macromolecules
1995, 28, 6311-6316.
(11) Schwab, P.; Grubbs, R. H.; Ziller, J. W. J. Am. Chem. Soc. 1996,
118, 100-110.
(12) Reference 4. See also: (a) Randall, M. L.; Tallarico, J. A.; Snapper,
M. L. J. Am. Chem. Soc. 1995, 117, 9610-9611. (b) Schneider, M. F.;
Blechert, S. Angew. Chem., Int. Ed. Engl. 1996, 35, 411-412. (c) Schuster,
M.; Pernerstorfer, J.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1996, 35,
1979-1980. (d) Tallarico, J. A.; Bonitatebus, P. J.; Snapper, M. L. J. Am.
Chem. Soc. 1997, 119, 7157-7158. (e) Kinoshita, A.; Sakakibara, N.; Mori,
M. J. Am. Chem. Soc. 1997, 119, 12388-12389.
Several factors and observations support the route proposed
in Scheme 3: (1) The styrenyl alkene is expected to react
preferentially (versus the disubstituted cyclic olefin) for steric
(9) For a recent report on the mechanism of the Ru-catalyzed ring-closing
metathesis, see: Dias, E. L.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem.
Soc. 1997, 119, 3887-3897.

Chromene Synthesis from Styrenyl Ethers
J. Am. Chem. Soc., Vol. 120, No. 10, 1998 2345
Scheme 3
Scheme 5
that the terminal alkene in 19 reacts more readily with the Ru
alkylidene to afford metal carbene 22. We argued that this
complex might be less reactive than 2 or 21, sequestering the
transition metal to discourage reactions with cyclooctenyl phenyl
ether 20. In the case of the intramolecular variants mentioned
above, as shown in Scheme 4, chelation can occur between the
metal and the cycloalkenyl π-system (23 f 24) to initiate
rearrangement.
angle is approximately 90°), 22 exhibits a JPH ) 4.4 Hz. These
data suggest that in complex 22, internal chelation between
phenolic oxygen and the transition metal perhaps alters the
relationship between Ha and the bound phosphine ligand, as
illustrated in Scheme 5 (compare 21 and 22).
Scheme 4
Regioselectivity in the Ru-Catalyzed Reactions of Disub-
stituted Styrenes. As mentioned above, we planned to obtain
optically pure styrenyl ethers through the Zr-catalyzed kinetic
resolution; subsequent metal-catalyzed rearrangement would
afford optically pure chromenes. This strategy followed our
initial unsuccessful attempts to resolve directly these 2-substi-
tuted heterocycles, an approach that was based on the effective
Zr-catalyzed kinetic resolution of dihydropyrans.13 However,
as shown in Scheme 6, the recovered starting material (13) was
obtained with <10% ee upon treatment with 10 mol % (R)-
(EBTHI)Zr-binol and 5 equiv of EtMgCl (70 °C, THF). We
conjectured that since the (EBTHI)Zr-catalyzed reaction pro-
vides efficient resolution only when asymmetric alkylation
occurs at the cyclic alkene site, it must therefore be that the
competitive reaction at the styrenyl terminal olefin renders the
resolution process largely ineffective; analysis of the 1H NMR
spectra of the unpurified reaction mixture supported this
contention. Catalytic resolution of disubstituted styrene 25 was
thus examined. Under identical conditions as mentioned above,
To establish additional support for the intermediacy of 22,
we attempted to synthesize and isolate this Ru-carbene
complex. We found that treatment of 19 with 1 equiv of 21 at
22 °C in CH2Cl2 for 24 h leads to the formation of 22 as a dark
brown solid (mp ) 200-201 °C). Inspection of the 400 MHz
1H NMR spectrum of 22 indicated that there is substantial
shielding of the alkylidene proton (Ha in 22), resulting in an
upfield shift of ∼2.5 ppm relative to the parent complex 21
(cf. Scheme 5). Furthermore, whereas there are no P-alky-
lidene couplings present in 2 or 21 (the P-Ru-C-H dihedral
Scheme 6
(13) (a) Morken, J. P.; Didiuk, M. T.; Visser, M. S.; Hoveyda, A. H. J.
Am. Chem. Soc. 1994, 116, 3123-3124. (b) Visser, M. S.; Heron, N. M.;
Didiuk, M. T.; Sagal, J. F.; Hoveyda, A. H. J. Am. Chem. Soc. 1996, 118,
4291-4298.

2346 J. Am. Chem. Soc., Vol. 120, No. 10, 1998
Harrity et al.
Scheme 7
28, both of which would be expected to undergo facile
rearrangement. Moreover, because the transformation is per-
formed at ambient temperature under ethylene, dimer formation
would be minimized. Accordingly, when (S)-25, obtained from
the Zr-catalyzed kinetic resolution of 25, was treated with 5
mol % 2 under an atmosphere of ethylene at 22 °C (CH2Cl2,
24 h), (S)-14 was obtained in 81% isolated yield and >99% ee
(Scheme 7). That is, as expected, the use of an ethylene
atmosphere proved to be necessary for preferential monomer
formation (10% of the derived dimer was also generated).
However, these results indicate that an ethylene atmosphere is
imperatiVe for efficient metal-catalyzed chromene formation as
well (25-30% yield of dimer 27 under argon).
The above hypothesis (i.e., initial cross-metathesis and
involvement of 13 and 28 in Scheme 8) was challenged soon
afterward. We discovered that when cyclohexenyl substrate 29
is treated to the same conditions as above, the unreacted starting
materialseven after prolonged reaction times (24 h)sstill bears
the disubstituted olefin (eq 3). That the six-membered styrenyl
cycloheptenyl styrenyl ether (S)-25 is obtained in >99% ee
(chiral GLC analysis) and 98% yield (based on percent
conversion). The cyclohexenyl substrate 26 is also resolved
by this method, albeit less efficiently: (S)-26 is obtained in 80%
ee after 62% conversion.
With an effective catalytic resolution procedure in hand, we
focused our attention on the Ru-catalyzed rearrangement of
disubstituted styrenyl ethers (e.g., 25). When 25 is treated with
10 mol % 2 under an atmosphere of Ar (Scheme 7), chromene
formation is sluggish: 25-30% of dimer (S,S)-27 is isolated
after 48 h at 45 °C, together with substantial amounts of
oligomeric materials. Initially, performing the reactions under
an atmosphere of ethylene was not considered. At the time,
we believed that the presence of the gaseous alkene only served
to avoid dimer formation and would do little to enhance reaction
efficiency. Furthermore, the use of ethylene with reactions run
at higher temperatures (e.g., 45 °C vs 22 °C) would be
experimentally cumbersome.
However, upon further consideration, we rationalized that
with a disubstituted styrene as substrate (e.g., 25), the desired
monomer chromenes could in fact be obtained cleanly if the
Ru-catalyzed reaction were to be carried out under ethylene (22
°C). This rationale, as illustrated in Scheme 8, was based on
the hypothesis that initial cross-metathesis between ethylene and
the styrene alkene would either lead to the formation of the
corresponding terminal styrene 13 or metal carbene complex
ether 29 would prove recalcitrant was expected, but the complete
absence of the cross-metathesis product 11 clearly indicated that
the rationale behind the successful Ru-catalyzed reaction of (S)-
25 may have been unfounded, despite the positive outcome
(efficient formation of 14 under ethylene).
To probe the alternative mechanistic pathways, we set out to
establish whether in fact, with disubstituted styrene substrates,
the active Ru-carbene complex also reacts with the styrenyl
olefin first. Toward this end, we found that when disubstituted
styrene 30 and cyclooctenyl phenyl ether 20 are treated with 5
Scheme 8

Chromene Synthesis from Styrenyl Ethers
J. Am. Chem. Soc., Vol. 120, No. 10, 1998 2347
mol % Ru complex 21 (eq 4), oligomeric products are formed
converted to LnRudCH2. Reactions of monosubstituted styrenes
do not require ethylene to proceed smoothly, because, as
illustrated in Scheme 3, with this class of starting materials,
the more reactive LnRudCH2 is formed following the first
catalytic cycle.
(2) Catalytic reactions of disubstituted styrenyl substrates lead
to significantly lower amounts of oligomeric products because
of the presence of ethylene. That is, if the initial transformation
of the Ru-carbene occurs with the “undesired regiochemistry”
(e.g., 25 f 32 in contrast to 25 f 31, Scheme 9), oligomer-
ization may predominate, particularly in instances where reclo-
sure of the carbocyclic ring is relatively sluggish (e.g., cyclo-
heptenyl substrates).
In contrast, as illustrated in Scheme 10, in the presence of
an ethylene atmosphere, the unwanted metal-carbene isomer
32 may rapidly be converted to triene 33. The resulting triene
might then react with LnRudCH2 to afford metal-carbene 31
and eventually chromene 14.
To test the validity of the above hypothesis, an authentic
sample of triene 33 was prepared and treated with 5 mol % Ru
complex 21 in dichloromethane at 22 °C (24 h). Thus, as
depicted in Scheme 11, when the ring-forming process is carried
out under an atmosphere of Ar, oligomeric products are
generated. In contrast, when the reaction is performed in the
presence of ethylene, 14 is readily obtained in 83% isolated
yield.
A significant implication of the mechanistic variance exhibited
in reactions of disubstituted styrenyl ethers is that the related
cyclopentenyl substrates should readily afford the desired
chromenes by the catalytic process (in contrast to complete lack
of reactivity of the derived terminal styrene 9, eq 5). Since the
in the same manner as observed when 20 is treated with the
transition metal catalyst in the absence of terminal styrene 19.
These experiments therefore suggested that with the more highly
substituted substrates (e.g., 25), in contrast to the reactions of
terminal styrenyl alkenes (e.g., 13 in Scheme 3), catalytic
chromene formation may commence with reaction at the
carbocyclic alkene site.14
The aforementioned mechanistic scenario suggests two critical
roles for ethylene in the catalytic reactions of disubstituted
styrenes:
(1) Transformations of the more highly substituted styrenyl
ethers are notably more facile under an atmosphere of ethylene
due to the presence of the more reactive LnRudCH2 (formed
by the reaction of 2 or 21 with ethylene). Under an atmosphere
of Ar and after the first turnover has transpired, LnRudCHCH3
is likely the participating catalyst. When the reaction is
performed under ethylene, LnRudCHCH3 is immediately
Scheme 9
metal-carbene complex first reacts with the carbocyclic alkene,
the strained tetracyclic intermediate, formed in reactions of
terminal styrenes (cf. 16 in Scheme 3), can be avoided. Indeed,
in contrast to 9, which is recovered unchanged with <5%
Scheme 10

2348 J. Am. Chem. Soc., Vol. 120, No. 10, 1998
Harrity et al.
Table 1. Synthesis of Functionalized Chromenes Through Ru- and
Scheme 11
Mo-Catalyzed Reactions of Styrenyl Ethersa
conversion (eq 5), treatment of 34 with 10 mol % 21 (CH2Cl2,
22 °C, 50 h) leads to the formation of 10 in 78% yield after
silica gel chromatography (eq 5).
The corresponding cyclohexenyl system 35 (Scheme 12)
remains relatively unreactive, however, even when the reaction
is performed under an ethylene atmosphere: after 24 h (10 mol
% 21, 1 atm. ethylene, CH2Cl2), only 10-20% of chromene 12
is obtained. This persistent lack of reactivity is presumably
because (i) the relatively strain-free six-membered ring is less
prone (relative to cyclopentenyl and cycloheptenyl structures)15
to react with LnRudCH2, and (ii) in the case ring rupture does
occur with the proper regiocontrol to afford 36 (vs 37, Scheme
12), reaction with the neighboring terminal alkene (leading back
to 35) should be kinetically more favored in comparison to that
with the disubstituted styrene olefin to deliver 12. Accordingly,
when triene 38 is subjected to these conditions, only 15-20%
of 12 is obtained (24 h). (See below for an effective catalyst
for reactions of cyclohexenyl substrates.)
Reactions of Functionalized Styrenyl Ethers. An advan-
tage of the methods described herein is that control of relative
stereochemistry on the carbocyclic substrate prior to catalytic
synthesis of chromenes can lead to the formation of various
functionalized heterocycles in excellent diastereochemical purity.
Several examples are illustrated in Table 1.16 Styrenyl ethers
of various ring sizes can be efficiently converted to their derived
chromenes in high yields. Two critical points with regard to
the data depicted in Table 1 merit mention.
a Conditions: 9 mol % 21, CH2Cl2, 22 °C, ethylene (1 atm), 36 h;
10 mol % 48, C6H6, 22 °C, 24 h. b Isolated yields after silica gel
chromatography.
in yields (mass balance remains >95%). As mentioned before,
the detrimental effect of the alcohol groups is likely due to
association with the Lewis acidic metal centers,18 resulting in
reduction of the metathesis activity of the transition metal
complexes.
(1) As shown in the entries of Table 1, with the more
functionalized starting substrates, chromene formation typically
occurs more efficiently if Schrock’s complex17 Mo(CHCMe2-
Ph)(N(2,6-(i-Pr)2C6H3))(OCMe(CF3)2)2 (48) is used intead of
Ru-based catalysts 2 or 21. An impressive example is shown
in entry 2 of Table 1; with 48 as catalyst, eVen the relatiVely
unreactiVe cyclohexenyl substrates such as 40a or 40b are
conVerted to the deriVed chromenes in excellent yields. Excep-
tions to this trend are found in the reactions of 42a and 42b.
Particularly striking is the process involving 42a, where the Ru
complex 21 affords 43a in 54% yield; in contrast, little or no
product is obtained with Mo system 48 as the precatalyst. The
lower activity of 48 is likely due to the higher Lewis acidic
nature of the Mo center, leading to catalyst inactivation through
chelation with the Lewis basic alcohol and the adjacent phenoxy
oxygen.
Kinetic Resolution of Functionalized Styrenyl Ethers. As
illustrated in Scheme 6 and discussed above, certain disubstituted
styrene ethers can be efficiently resolved through the Zr-
catalyzed kinetic resolution. As illustrated in eq 6, optically
pure cycloheptenyl ether 42c is obtained by the Zr-catalyzed
process (>98% ee at 65% conv by analysis of 400 MHz 19F
NMR of the derived (S)-MTPA ester). The successful catalytic
resolution makes the parent alcohol and the derived benzyl ether
derivatives 42a and 42b accessible in the optically pure form
as well. However, this approach cannot be successfully applied
to all the substrates shown in Table 1. For example, under
identical conditions, 38b is recovered in only 52% ee after 60%
conversion. In a similar vein, 40a is recovered in 30% ee after
55% conversion. Cycloheptenyl substrates shown in entries 4
and 5 undergo significant decomposition under the Zr-catalyzed
(2) The presence of an unprotected hydroxyl function, such
as those shown in entries 3 and 4, result in notable diminution
(14) For a related regioselectivity variance as a result of alkene
substitution pattern, see: Zuercher, W. J.; Hashimoto, M.; Grubbs, R. H.
J. Am. Chem. Soc. 1996, 118, 6634-6640.
(15) For a study on the ring-opening metathesis of cyclohexene, see:
Patton, P. A.; Lillya, C. P.; McCarthy, T. J. Macromolecules 1986, 19,
1266-1268.
(16) See the Supporting Information section for the synthesis of requisite
starting materials.
(17) (a) Schrock, R. R.; Murdzek, J. S.; Bazan, G. C.; Robbins, J.;
DiMare, M.; O’Regan, M. J. Am. Chem. Soc. 1990, 112, 3875-3886. (b)
Bazan, G. C.; Schrock, R. R.; Cho, H.-N.; Gibson, V. C. Macromolecules
1991, 24, 4495-4502.
(18) For a hydroxyl-directed olefination of ketones with 48 as catalyst,
see: Fujimura, O.; Fu, G. C.; Rothemund, P. W. K.; Grubbs, R. H. J. Am.
Chem. Soc. 1995, 117, 2355-2356.

Chromene Synthesis from Styrenyl Ethers
J. Am. Chem. Soc., Vol. 120, No. 10, 1998 2349
Scheme 12
carbomagnesation conditions. These observations clearly in-
dicate that future work must be directed toward the development
of more general methods that provide a wider range of styrenyl
ethers in high optical purity. A more enticing and economical
approach would be the development of a chiral metathesis
catalyst that effects the chromene formation and resolves the
two styrene ether enantiomers simultaneously.
are reported as follows: chemical shift, integration, multiplicity
(s ) singlet, d ) doublet, t ) triplet, q ) quartet, br ) broad,
m ) multiplet), coupling constants (Hz), and assignment. 13C
NMR spectra were recorded on a Varian Unity 300 (75 MHz)
or Varian GN-400 (100 MHz) with complete proton decoupling.
Chemical shifts are reported in ppm from tetramethylsilane with
the solvent as the internal reference (CDCl3: δ 77.7 ppm). An
Alltech Associates DB-1 capillary column (30 m × 0.32 mm)
was used to determine conversions. Enantiomer ratios were
determined by GLC with an ALPHA-DEX 120 (30 m × 0.25
mm) chiral column by Supelco. High-resolution mass spectra
obtained at the Mass Spectrometry Facility of the University
of Illinois (Urbana-Champaign, Illinois). Combustion analysis
data could not be obtained due to the instability of 2-substituted
chromene products. Since the chromene products decompose
rapidly (within approximately 30 min) at 22 °C, spectral data
were obtained immediately after silica gel chromatography.
Samples for HRMS were stored under argon in a freezer at -20
°C until immediately prior to analysis.
All reactions were conducted in oven-dried (135 °C) and
flame-dried glassware under an inert atmosphere of dry argon.
Tetrahydrofuran was distilled from sodium metal/benzophenone
ketyl. Dichloromethane was distilled from calcium hydride.
Ethylmagnesium chloride was prepared from ethyl chloride and
Mg (turnings), which were purchased from Aldrich and used
without further purification. (EBTHI)Zr-binol was prepared and
resolved by methods of Brintzinger and Buchwald.19 Nonra-
cemic (EBTHI)Zr-binol catalyst batches were stored under argon
in a glovebox. (PCy3)2Cl2RudCHCHdCPh2 and (PCy3)2Cl2-
RudCHPh were prepared by the method of Grubbs.3
Mo(CHCMe2Ph)(N(2,6-(i-Pr)2C6H3))(OCMe(CF3)2)2 was pre-
pared by the method of Schrock.17
Conclusions. A metal-catalyzed reaction is disclosed that
converts allylic styrenyl ethers to 2-substituted chromenes in
an efficient manner. Although reactions of terminal styrenes
catalyzed by Ru-based catalysts 2 or 21 proceed through initial
reaction with the styrenyl olefin, catalytic transformations of
disubstituted substrates appear to be initiated by interaction of
the metal-carbene complex with the carbocyclic π system. Use
of an ethylene atmosphere significantly enhances the generality
and utility of the process: (1) It leads to near exclusive formation
of monomeric chromenes. (2) It allows for a more efficient
conversion of disubstituted styrenes to the corresponding
chromenes. (3) It permits the catalytic cycle to bypass a strained
intermediate (cf. 16 in Scheme 3), thus enabling additional
substrates to be readily converted to chromenes (reactions of
38 and 40a,b). The use of Schrock’s Mo-based catalyst 48
further enhances the power of this transition metal-catalyzed
process by effecting efficient reactions of functionalized sub-
strates (e.g., entry 2 of Table 1). An important corollary to
these transformations is that, in certain cases, the starting
material can be obtained optically pure through the use of Zr-
catalyzed kinetic resolution (Scheme 6 and eq 6). Nonetheless,
studies aimed at the development of more general technologies
that afford nonracemic styrene ethers are required. These
investigations and the total synthesis of medicinally important
agents that examine and challenge the utility of the methods
described herein are in progress.
Representative Experimental Procedure for the Ru-
Catalyzed Rearrangement of (2S)-((1S)-(tert-Butyldimeth-
ylsiloxy)-4-pentenyl)-2H-3,4-dihydrobenzopyran (40b f 41b).
A flame-dried 10 mL round-bottom flask was charged with 40b
(40 mg, 0.116 mmol) and CH2Cl2 (1.16 mL). Ruthenium
complex 2 (8.6 mg, 0.01 mmol, 9 mol %) was added in three
equal portions every 12 h. The reaction vessel was initially
Experimental Section
General Information. Infrared (IR) spectra were recorded
on a Perkin-Elmer 781 spectophotometer, νmax in cm-1. Bands
are characterized as broad (br), strong (s), medium (m), and
weak (w). 1H NMR spectra were recorded on a Varian Unity
300 (300 MHz) or Varian GN-400 (400 MHz). Chemical shifts
are reported in ppm from tetramethylsilane with the solvent
resonance as the internal standard (CDCl3: δ 7.26 ppm). Data
(19) (a) Wild, F. R. W. P.; Wasiucionek, M.; Huttner, G.; Brintzinger,
H. J. Organomet. Chem. 1985, 288, 63-67. (b) Grossman, R. B.; Doyle,
R. A.; Buchwald, S. L. Organometallics 1991, 10, 1501-1505.

2350 J. Am. Chem. Soc., Vol. 120, No. 10, 1998
Harrity et al.
flushed with ethylene gas (vacuum-ethylene flush cycle was
repeated three times); the mixture was kept under an atmosphere
of ethylene (balloon). Stirring was allowed to continue at 22
°C for a total of 36 h. The reaction was quenched by the
addition of 0.5 mL of undistilled ethyl vinyl ether;20 volatiles
were subsequently removed in vacuo. The resulting residue
was purified through silica gel chromatography to afford
chromene 41b (13.8 mg, 36% yield). IR (NaCl, film): 3073
(w), 2955 (m), 2929 (m), 2856 (m), 1458 (w), 1257 (m), 1230
(m, 1H, HCdCH2), 5.64 (dd, J ) 6.4, 3.6 Hz, 1H, aryl
(H)CdCH), 5.03 (d, J ) 17.2 Hz, 1H, HCdCHH), 4.98 (d, J
) 10.4 Hz, 1H, HCdCHH), 4.92-4.89 (m, 1H, CHdCHCHO),
4.60 (d, J ) 10.8 Hz, 1H, aryl CHHsO), 4.52 (d, J ) 10.8 Hz,
1H, aryl CHHsO), 3.62-3.58 (m, 1H, HCsOBn), 2.42-2.35
(m, 1H, CH2dCHCHH), 2.29-2.22 (m, 1H, CH2dCHCHH).
13C NMR (100 MHz, CDCl3): δ 155.1, 139.1, 135.5, 130.0,
129.0, 128.5, 128.3, 127.2, 125.8, 122.9, 122.4, 121.8, 117.9,
116.5, 80.5, 78.0, 73.7, 35.6. HRMS Calcd for C20H20O2:
292.1463. Found: 292.1464.
(m), 1085 (m), 835 (m), 775 (m), 751 (m) cm-1 1H NMR
.
(400 MHz, CDCl3): δ 7.07 (dt, J ) 7.7, 1.6 Hz, 1H, aromatic
CH), 6.92 (dd, J ) 7.2, 1.6 Hz, 1H, aromatic CH), 6.81 (dt, J
) 7.3, 0.8 Hz, 1H, aromatic CH), 6.72 (dd, J ) 8.1, 0.8 Hz,
1H, aromatic CH), 6.43 (dd, J ) 10.0, 1.9 Hz, 1H, aromatic
(H)CdCH), 5.87-5.78 (m, 1H, HCdCH2), 5.76 (dd, J ) 10.0,
2.8 Hz, 1H, aromatic (H)CdCH), 5.04-4.99 (m, 1H, HCdCHH),
4.96-4.93 (m, 1H, HCdCHH), 4.92-4.90 (m, 1H,
HCdCHsCHsO), 3.91 (dt, J ) 8.6, 4.0 Hz, 1H, HCsOTBS),
2.28-2.19 (m, 1H, CHHCH2), 2.13-2.04 (m, 1H, CHHCH2),
1.82-1.74 (m, 1H, CH2CHH), 1.61-1.51 (m, 1H, CH2CHH),
0.88 (s, 9H, C(CH3)3), 0.07 (s, 6H, SiCH3). 13C NMR (100
MHz, CDCl3): δ 154.3, 139.4, 129.7, 127.2, 125.6, 122.9, 122.4,
121.6, 116.1, 115.2, 78.6, 73.8, 32.3, 30.5, 26.5, 18.8, -3.7,
-3.9. HRMS Calcd for C20H30O2Si (M - H): 329.1937.
Found: 329.1939.
Representative Experimental Procedure for the Molyb-
denum-Catalyzed Rearrangement of (2S)-((1S)-(tert-Butyl-
dimethylsiloxy)-4-pentenyl)-2H-3,4-dihydrobenzopyran (40b
f 41b). Styrenyl ether 40b (52.0 mg, 0.15 mmol) was placed
in a 10 mL round-bottom flask. After the addition of degassed
benzene (1.51 mL), the resulting solution was charged with Mo
catalyst 48 (11.6 mg, 0.015 mmol, 10 mol %). The reaction
vessel was flushed with ethylene (vacuum-ethylene flush cycle
was repeated three times), equipped with an ethylene-filled
balloon, and stirred at 22 °C for 24 h. The reaction was
quenched by the addition of 500 mL of undistilled ethyl vinyl
ether, after which the volatiles were subsequently removed in
vacuo. The resulting residue was purified through silica gel
chromatography to afford chromene 41b (39.2 mg, 79% yield).
(2S)-((1S)-(tert-Butyldimethylsiloxy)-3-butenyl)-2H-3,4-di-
hydrobenzopyran (39b). IR (NaCl): 3075 (w), 2949 (m), 2931
(m), 2886 (m), 2861 (m), 1489 (m), 1458 (m), 1224 (m), 1088
(s), 835 (s), 775 (m) cm-1 1H NMR (400 MHz, CDCl3): δ
.
7.08 (dt, J ) 7.2, 1.6 Hz, 1H, aromatic CH), 6.92 (dd, J ) 7.2,
1.6 Hz, 1H, aromatic CH), 6.82 (dt, J ) 7.2, 1.6 Hz, 1H,
aromatic CH), 6.74 (d, J ) 7.2 Hz, 1H, aromatic CH), 6.44
(dd, J ) 9.6, 1.6 Hz, 1H, aryl (H)CdCH), 5.87 (dddd, J )
14.0, 14.0, 10.0, 7.7 Hz, 1H, HCdCH2), 5.75 (dd, J ) 10.0,
3.2 Hz, 1H, aryl (H)CdCH), 5.11-5.04 (m, 1H, HCdCHH),
4.91-4.89 (m, 1H, HCdCHH), 3.92 (ddd, J ) 8.0, 8.0, 4.4
Hz, 1H, HCsOTBS), 2.50-2.44 (m, 1H, CHHCH2), 2.24 (ddd,
J ) 14.0, 14.0, 7.6, 1H, CH2dCHCHH), 0.87 (s, 9H, C(CH3)3),
0.07 (s, 3H, SiCH3), 0.05 (s, 3H, SiCH3). 13C NMR (100 MHz,
CDCl3): δ 154.3, 135.9, 129.7, 127.2, 125.7, 122.8, 122.3,
121.5, 117.9, 116.2, 78.5, 74.3, 38.0, 26.5, 18.8, -3.8, -3.8.
HRMS Calcd for C19H28O2Si (M - H): 315.1781. Found:
315.1779.
(2S)-((1S)-(Benzyloxy)-4-pentenyl)-2H-3,4-dihydroben-
zopyran (41a). 1H NMR (400 MHz, CDCl3): δ 7.36-7.29
(m, 5H, aromatic CH), 7.12 (dt, J ) 7.6, 1.6 Hz, 1H, aromatic
CH), 6.97 (dd, J ) 7.6, 1.6 Hz, 1H, aromatic CH), 6.86 (dt, J
) 7.6, 1.6 Hz, 1H, aromatic CH), 6.80 (d, J ) 8.0 Hz, 1H,
aromatic CH), 6.47 (dd, J ) 10.0, 1.6 Hz, 1H, aryl (H)CdCH),
5.85-5.74 (m, 1H, HCdCH2), 5.76 (dd, J ) 10.0, 3.6 Hz, 1H,
aryl (H)CdCH), 5.05-4.94 (m, 2H, HCdCH2), 4.75 (d, J )
11.6 Hz, 1H, aryl CHHsO), 4.56 (d, J ) 11.6 Hz, 1H, aryl
CHHsO), 3.66 (ddd, J ) 9.2, 5.6, 3.6 Hz, 1H, HCsOBn),
2.34-2.25 (m, 1H, CH2dCHCHH), 2.18-2.08 (m, 1H,
CH2dCHCHH), 1.80-1.61 (m, 2H, CH2dCHCH2CH2). 13C
NMR (100 MHz, CDCl3): δ 154.0, 139.3, 139.1, 130.0, 129.0,
128.6, 127.3, 125.7, 123.0, 122.5, 121.8, 116.4, 115.5, 80.3,
77.4, 73.9, 30.5, 30.4. HRMS Calcd for C21H22O2: 306.1620.
Found: 306.1620.
2-(3-Butenyl)-2H-3,4-dihydrobenzopyran
(NaCl): 3062 (w), 2936 (m), 1483 (s), 1457 (m), 1231 (s), 1117
(m), 752 (m) cm-1 1H NMR (400 MHz, CDCl3): δ 7.09 (dt,
(10).
IR
.
J ) 7.6, 1.6 Hz, 1H, aromatic CH), 6.95 (dd, J ) 7.6, 1.6 Hz,
1H, aromatic CH), 6.83 (dt, J ) 7.6, 1.2 Hz, 1H, aromatic CH),
6.76 (d, J ) 8.0 Hz, 1H, aromatic CH), 6.38 (d, J ) 10.0 Hz,
1H, aryl (H)CdCH), 5.81 (dddd, J ) 17.2, 13.6, 10.4, 6.8 Hz,
1H, alkyl HCdCH2), 5.67 (dd, J ) 9.6, 3.2 Hz, 1H, aryl
(H)CdCH), 5.01 (dd, J ) 16.8, 1.2 Hz, 1H, HCdCHH), 4.96
(dd, J ) 10.4, 0.8 Hz, 1H, HCdCHH), 4.87-4.85 (m, 1H,
HCdCHCHsO), 2.12-2.07 (m, 2H, CH2sCHCH2) 1.85-1.75
(m, 1H, OsCHCHH), 1.72-1.60 (m, 1H, OsCHCHH). 13C
NMR (100 MHz, CDCl3): δ 154.0, 138.6, 129.8, 127.1, 126.3,
124.7, 122.6, 121.6, 116.6, 115.7, 75.1, 35.1, 29.7. HRMS
Calcd for C13H14O: 186.1045. Found: 186.1041.
(2S)-((1S)-(tert-Butyldimethylsiloxy)-4-pentenyl)-2H-3,4-
dihydrobenzopyran (41b). IR (NaCl): 3073 (w), 2955 (m),
2929 (m), 2856 (m), 1458 (w), 1257 (m), 1230 (m), 1085 (m),
.
835 (m), 775 (m), 751 (m) cm-1 1H NMR (400 MHz,
CDCl3): δ 7.07 (dt, J ) 7.7, 1.6 Hz, 1H, aromatic CH), 6.92
(dd, J ) 7.2, 1.6 Hz, 1H, aromatic CH), 6.81 (dt, J ) 7.3, 0.8
Hz, 1H, aromatic CH), 6.72 (dd, J ) 8.1, 0.8 Hz, 1H, aromatic
CH), 6.43 (dd, J ) 10.0, 1.9 Hz, 1H, aryl (H)CdCH), 5.87-
5.78 (m, 1H, HCdCH2), 5.76 (dd, J ) 10.0, 2.8 Hz, 1H, aryl
(H)CdCH), 5.04-4.99 (m, 1H, HCdCHH), 4.96-4.93 (m, 1H,
HCdCHH), 4.92-4.90 (m, 1H, HCdCH-CHsO), 3.91 (dt,
J ) 8.6, 4.0 Hz, 1H, HCsOTBS), 2.28-2.19 (m, 1H,
CHHCH2), 2.13-2.04 (m, 1H, CHHCH2), 1.82-1.74 (m, 1H,
CH2CHH), 1.61-1.51 (m, 1H, CH2CHH), 0.88 (s, 9H, C(CH3)3),
0.07 (s, 6H, SiCH3). 13C NMR (100 MHz, CDCl3): δ 154.3,
139.4, 129.7, 127.2, 125.6, 122.9, 122.4, 121.6, 116.1, 115.2,
78.6, 73.8, 32.3, 30.5, 26.5, 18.8, -3.7, -3.9. HRMS Calcd
for C20H30O2Si (M - H): 329.1937. Found: 329.1939.
(2S)-((1S)-Hydroxy-4-hexenyl)-2H-3,4-dihydrobenzopy-
ran (43a). IR (NaCl, film): 3440 (br), 3075 (w), 2930 (m),
(2S)-((1S)-(Benzyloxy)-3-butenyl)-2H-3,4-dihydrobenzopy-
ran (39a). IR (NaCl): 3075 (w), 2949 (m), 2931 (m), 2861
(m), 2886 (m), 1489 (m), 1458 (s), 1224 (m), 1088 (s), 835 (s),
776 (s) cm-1 1H NMR (400 MHz, CDCl3): δ 7.29-7.16 (m,
.
5H, aromatic CH), 7.02 (dt, J ) 7.2, 1.6 Hz, 1H, aromatic CH),
6.87 (dd, J ) 7.2, 1.6 Hz, 1H, aromatic CH), 6.75 (dt, J ) 7.2,
1.6 Hz, 1H, aromatic CH), 6.70 (d, J ) 8.4 Hz, 1H, aromatic
CH), 6.37 (d, J ) 10.0, Hz, 1H, aryl (H)CdCH), 5.86-5.76
(20) (a) Reference 3. (b) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs,
R. H. Angew. Chem., Int. Ed. Engl. 1995, 34, 2039-2041.
1486 (s), 1457 (s), 1230 (s), 752 (m) cm-1 1H NMR (400
.

Chromene Synthesis from Styrenyl Ethers
J. Am. Chem. Soc., Vol. 120, No. 10, 1998 2351
MHz, CDCl3): δ 7.12 (dt, J ) 7.6, 1.6 Hz, 1H, aromatic CH),
6.97 (dd, J ) 7.6, 1.2 Hz, 1H, aromatic CH), 6.87 (dt, J ) 7.6,
1.6 Hz, 1H, aromatic CH), 6.82 (d, J ) 7.6 Hz, 1H, aromatic
CH), 6.49 (d, J ) 10.4 Hz, 1H, aryl (H)CdCH), 5.82 (dddd, J
) 16.8, 13.2, 10.4, 6.4 Hz, 1H, HCdCH2), 5.78 (dd, J ) 10.0,
3.6 Hz, 1H, aryl (H)CdCH), 5.02 (dd, J ) 16.8, 1.6 Hz, 1H,
HCdCHH), 4.97 (dd, J ) 10.0, 1.6 Hz, 1H, HCdCHH), 4.69-
4.67 (m, 1H, aryl (H)CdCH-CHsO), 3.80-3.75 (m, 1H,
HCsOH), 2.40 (d, J ) 3.6 Hz, 1H, CsOH), 2.13-2.07 (m,
2H, CH2C(H)dCH2), 1.70-1.46 (m, 4H, CH2CH2). 13C NMR
(100 MHz, CDCl3): δ 153.4, 139.2, 130.1, 127.4, 126.2, 122.8,
122.4, 122.1, 116.5, 115.4, 79.1, 73.6, 34.3, 31.9, 25.4. HRMS
Calcd for C15H18O2: 230.1307. Found: 230.1307.
hydrobenzopyran (45c). IR (NaCl): 3081 (w), 3043 (w), 3050
(w), 2962 (s), 2936 (s), 2867 (m), 1646 (w), 1608 (w), 1495
(m), 1256 (m), 1237 (m), 1036 (m), 834 (s), 778 (s), 752 (m)
cm-1 1H NMR (400 MHz, CDCl3): δ 7.09 (dt, J ) 7.6, 1.6
.
Hz, 1H, aromatic CH), 6.95 (dd, J ) 7.6, 1.6 Hz, 1H, aromatic
CH), 6.84 (dt, J ) 7.6, 1.6 Hz, 1H, aromatic CH), 6.77 (d, J )
7.6 Hz, 1H, aromatic CH), 6.38 (d, J ) 9.6 Hz, 1H, aryl
(H)CdCH), 5.80 (ddd, J ) 13.2, 10.8, 6.0 Hz, 1H, HCdCH2),
5.67 (dd, J ) 10.0, 3.2 Hz, 1H, aryl (H)CdCH), 5.15 (dd, J )
12.5, 1.2 Hz, 1H, HCdCHH), 5.03 (dd, J ) 10.0, 1.2 Hz, 1H,
HCdCHH), 4.86-4.82 (m, 1H, HCdCHsCHsO), 4.11-4.10
(m, 1H, HCsOTBS), 1.84-1.46 (m, 6H, CH2CH2CH2), 0.90
(s, 9H, C(CH3)3), 0.04 (s, 3H, SiCH3), 0.03 (s, 3H, SiCH3). 13
C
(2S)-((1S)-(Benzyloxy)-5-hexenyl)-2H-3,4-dihydrobenzo-
pyran (43b). IR (NaCl): 2923 (s), 2860 (m), 1487 (m), 1457
NMR (100 MHz, CDCl3): δ 154.2, 142.3, 129.7, 127.1, 126.5,
124.6, 122.7, 121.6, 116.6, 114.3, 75.7, 74.4, 38.5, 36.1, 26.6,
21.2, 18.9, -3.7, -4.1. HRMS Calcd for C21H32O2Si: 344.2172.
Found: 344.2172.
(s), 1230 (m), 1113 (w) cm-1 1H NMR (400 MHz, CDCl3):
.
δ 7.39-7.29 (m, 5H, aromatic CH), 7.12 (dt, J ) 7.6, 1.6 Hz,
1H, aromatic CH), 6.97 (dd, J ) 7.6, 1.6 Hz, 1H, aromatic CH),
6.86 (dt, J ) 7.6, 0.8 Hz, 1H, aromatic CH), 6.81 (d, J ) 8.0
Hz, 1H, aromatic CH), 6.47 (d, J ) 10.0 Hz, 1H, aryl
(H)CdCH), 5.84-5.74 (m, 1H, CHdCH2), 5.75 (dd, J ) 10.0,
3.6 Hz, 1H, aryl (H)CdCH), 5.03-4.95 (m, 2H, HCdCH2),
4.75 (d, J ) 11.2 Hz, 1H, aryl CHHsO), 4.57 (d, J ) 11.2 Hz,
1H, aryl CHHsO), 3.66-3.62 (m, 1H, HCsOBn), 2.06-2.01
(m, 2H, CH2dCHCH2), 1.70-1.40 (m, 4H, CH2CH2). 13C
NMR (100 MHz, CDCl3): δ 139.3, 129.9, 129.1, 129.0, 128.6,
128.5, 128.3, 127.2, 125.6, 123.1, 122.5, 121.8, 116.5, 115.3,
80.8, 77.5, 34.4, 30.6, 25.6. HRMS Calcd for C22H24O2:
320.1776. Found: 320.1776.
(2S)-((4S)-(Benzyloxy)-5-hexenyl)-2H-3,4-dihydrobenzo-
pyran (47a). IR (NaCl): 3640 (w), 3027 (w), 2929 (s), 2850
(s), 1638 (w), 1601 (w), 1479 (m), 1455 (m), 1234 (m), 1087
.
(m), 757 (m), 696 (m) cm-1 1H NMR (400 MHz, CDCl3): δ
7.40-7.26 (m, 5H, aromatic CH), 7.10 (dt, J ) 7.6, 1.2 Hz,
1H, aromatic CH), 6.96 (dd, J ) 7.6, 1.2 Hz, 1H, aromatic CH),
6.84 (t, J ) 7.6 Hz, 1H, aromatic CH), 6.77 (d, J ) 7.6 Hz,
1H, aromatic CH), 6.38 (d, J ) 9.6 Hz, 1H, aryl (H)CdCH),
5.75 (ddd, J ) 15.2, 10.0, 8.0 Hz, 1H, HCdCH2), 5.66 (dd, J
) 9.6, 3.6 Hz, 1H, aromatic (H)CdCH), 5.25-5.23 (m, 1H,
HCdCHH), 4.84-4.82 (m, 1H, HCdCHsCHsO), 4.60 (d, J
) 12.8 Hz, 1H, aryl CHH-O), 4.35 (d, J ) 12.8 Hz, 1H, aryl
CHHsO), 3.77-3.72 (m, 1H, HCsOBn), 1.83-1.24 (m, 6H,
CH2CH2CH2). 13C NMR (100 MHz, CDCl3): δ 154.2, 139.6,
139.4, 129.7, 129.0, 128.5, 128.1, 127.1, 126.5, 124.6, 122.6,
121.6, 117.9, 116.6, 81.0, 75.7, 70.7, 35.9, 35.8, 21.5. HRMS
Calcd for C22H24O2 (M - H): 319.1698. Found: 319.1696.
(2S)-((1S)-(tert-Butyldimethylsiloxy)-5-hexenyl)-2H-3,4-di-
hydrobenzopyran (43c). IR (NaCl): 3075 (w), 2962 (m), 2942
(s), 2855 (m), 1489 (m), 1457 (m), 1231 (m), 1205 (m), 1086
(m), 778 (s) cm-1 1H NMR (400 MHz, CDCl3): δ 7.08 (dt,
.
J ) 7.6, 1.6 Hz, 1H, aromatic CH), 6.94 (dd, J ) 7.2, 1.6 Hz,
1H, aromatic CH), 6.82 (dt, J ) 7.6, 1.6 Hz, 1H, aromatic CH),
6.75 (d, J ) 8.0 Hz, 1H, aromatic CH), 6.43 (dd, J ) 10.0, 1.6
Hz, 1H, aryl (H)CdCH), 5.86-5.75 (m, 1H, HCdCH2), 5.77
(dd, J ) 10.0, 2.8 Hz, 1H, aryl (H)CdCH), 5.00 (dd, J ) 17.2,
1.6 Hz, 1H, HCdCHH), 4.95 (dd, J ) 10.4, 1.6 Hz, 1H,
HCdCHH), 4.92-4.89 (m, 1H, HCdCHsCHsO), 3.90 (dt,
J ) 8.0, 4.0 Hz, 1H, HCsOTBS), 2.12-2.01 (m, 2H,
CHdCHCH2), 1.73-1.43 (m, 4H, CH2dCHCH2CH2CH2), 0.90
(2S)-((4S)-(tert-Butyldimethylsiloxy)-5-hexenyl)-2H-3,4-di-
hydrobenzopyran (47b). IR (NaCl): 3081 (w), 3043 (w), 2962
(s), 2924 (s), 2855 (m), 1495 (m), 1457 (m), 1231 (m), 1081
.
(m), 841 (s), 778 (s) cm-1 1H NMR (400 MHz, CDCl3): δ
7.09 (dt, J ) 7.8, 1.6 Hz, 1H, aromatic CH), 6.95 (dd, J ) 7.2,
1.6 Hz, 1H, aromatic CH), 6.84 (dt, J ) 7.6, 1.2 Hz, 1H,
aromatic CH), 6.77 (d, J ) 8.0 Hz, 1H, aromatic CH), 6.39
(dd, J ) 9.8, 0.8 Hz, 1H, aryl (H)CdCH), 5.84-5.76 (m, 1H,
HCdCH2), 5.67 (dd, J ) 9.8, 3.2 Hz, 1H, aryl (H)CdCH),
5.17-5.12 (m, 1H, HCdCHH), 5.04-5.01 (m, 1H, HCdCHH),
4.85-4.83 (m, 1H, HCdCHsCHsO), 4.12-4.07 (m, 1H,
HCsOTBS), 1.84-1.42 (m, 6H, CH2CH2CH2), 0.90 (s, 9H,
C(CH3)3), 0.05 (s, 3H, SiCH3), 0.03 (s, 3H, SiCH3). 13C NMR
(100 MHz, CDCl3): δ 154.2, 142.4, 129.7, 127.1, 126.5, 124.6,
122.7, 121.6, 116.6, 114.3, 75.7, 74.4, 38.5, 36.0, 26.6, 21.3,
18.9, -3.6, -4.1. HRMS Calcd for C21H32O2Si: 344.2172.
Found: 344.2169.
(s, 9H, C(CH3)3), 0.09 (s, 3H, SiCH3), 0.08 (s, 3H, SiCH3). 13
C
NMR (100 MHz, CDCl3): δ 154.4, 139.4, 129.9, 127.2, 125.5,
123.0, 122.5, 121.5, 116.2, 115.1, 78.7, 74.2, 34.5, 32.5, 26.5,
26.7, 18.8, -3.7, -3.9. HRMS Calcd for C21H34O2Si (M -
H): 345.2250. Found: 345.2241.
(2S)-((4R)-(Benzyloxy)-5-hexenyl)-2H-3,4-dihydrobenzo-
pyran (45b). IR (NaCl, film): 3024 (m), 2930 (s), 2855 (m),
1489 (s), 1231 (s), 1092 (m), 752 (s) cm-1 1H NMR (400
.
MHz, CDCl3): δ 7.37-7.23 (m, 5H, aromatic CH), 7.10 (dt, J
) 7.6, 1.6 Hz, 1H, aromatic CH), 6.96 (dd, J ) 7.2, 1.6 Hz,
1H, aromatic CH), 6.85 (dt, J ) 7.6, 1.6 Hz, 1H, aromatic CH),
6.79 (d, J ) 8.0 Hz, 1H, aromatic CH), 6.39 (d, J ) 10.0 Hz,
1H, aryl (H)CdCH), 5.25 (dd, J ) 3.6, 0.8 Hz, 1H, HCdCHH),
5.24-5.20 (m, 1H, HCdCHH), 4.85-4.83 (m, 1H,
HCdCHsCHsO), 4.61 (d, J ) 11.8 Hz, 1H, aryl CHHsO),
4.36 (d, J ) 11.8 Hz, 1H, aryl CHHsO), 3.78-3.73 (m, 1H,
HCsOBn), 1.84-1.50 (m, 6H, CH2CH2CH2). 13C NMR (100
MHz, CDCl3): δ 154.1, 139.6, 139.4, 129.7, 127.0, 128.4, 128.1,
127.1, 126.5, 124.6, 122.6, 121.6, 117.9, 116.6, 81.0, 75.7, 70.7,
36.0, 35.9, 21.5. HRMS Calcd for C22H24O2 (M - H):
319.1698. Found: 319.1696.
Acknowledgment. The National Institutes of Health (GM-
47480) and the National Science Foundation (NSF-9632278)
generously supported this research. Additional support was
provided by Johnson and Johnson. A.H.H. is an Alfred P. Sloan
Fellow and a Dreyfus Teacher-Scholar. D.S.L. is a Department
of Education GAANN Fellow.
Supporting Information Available: 1H NMR and 13C NMR
spectra data for select reaction products (23 pages). See any
current masthead page for ordering and Web access instructions.
(2S)-((4R)-(tert-Butyldimethylsiloxy)-5-hexenyl)-2H-3,4-di-
JA9739796