Molybdenum(IV) Complexes as Efficient, Lewis Acidic Catalysts for Allylic Substitution. Formation of C-C and C-N Bonds

Full text of DOI:10.1021/jo990372u

5308
J . Org. Chem. 1999, 64, 5308-5311
Sch em e 1
Molybd en u m (IV) Com p lexes a s Efficien t,
Lew is Acid ic Ca ta lysts for Allylic
Su bstitu tion . F or m a tion of C-C a n d C-N
Bon d s
Andrei V. Malkov,† Paul Spoor,† Victoria Vinader,‡ and
Pavel Kocˇovsky´*,†
electron-rich aromatics and trimethylsilyl azide, respec-
tively.
Department of Chemistry, University of Leicester,
Leicester LE1 7RH, U.K., and GlaxoWellcome, Research and
Development, Medicines Research Centre, Stevenage,
Herts. SG1 2NY, U.K.
Resu lts a n d Discu ssion
P r ep a r a tion of Mo(IV) Ca ta lysts. In a redox reac-
tion with 2,4-pentanedione, molybdenum(V) chloride is
known to produce the corresponding Mo(IV) bisacac
complex A as a relatively stable solid (Scheme 2).6,7
According to one original procedure,6a the reaction is
simply carried out by heating MoCl5 in 2,4-pentanedione
so that the latter serves as a reagent, reducing agent,
and solvent. An alternative procedure6b employs aceto-
nitrile as the solvent and reducing agent; a mixture
MoCl5 and MeCN is first refluxed to reduce MoCl5 to
MoCl4, followed by addition of 2,4-pentanedione. Of the
two procedures, we found the latter to be more practicable
as it exhibited better reproducibility and gave a cleaner
product, which could be easily isolated as a precipitate.
Of course, complex A can also be prepared directly6a from
2,4-pentanone and MoCl4, which, however, is consider-
ably more expensive than MoCl5.
Received March 2, 1999
In tr od u ction
In transition-metal-catalyzed allylic substitution
(Scheme 1), allylic acetates and carbonates play a prime
role as electrophilic substrates. Numerous studies and
applications using Pd(0),1 Mo(0),2 and W(0)3 complexes
and a variety of reacting partners show how general this
reaction is. Although the literature in this area is
dominated by C-C bond-forming processes, examples of
C-N, C-O, C-Cl, and C-S bond construction have also
been reported.1 In contrast to the wide use of allylic esters
and related derivatives, direct application of the parent
allylic alcohols in these reactions is rare.4
As part of a program aimed at designing new, more
reactive molybdenum and tungsten complexes as replace-
ment for the more expensive Pd(0) catalysts, we have
recently shown that the Lewis-acidic Mo(II) complexes
Mo(CO)5(OTf)2, [Mo(CO)4Br2]2, and Mo(CO)3(MeCN)2-
(SnCl3)Cl and their W(II) counterparts are capable of
catalyzing allylic substitution at ambient temperature.
Using a series of allylic acetates, we have demonstrated
efficient C-C bond-forming reactions not only with the
usual malonate-type nucleophiles but also with silyl enol
ethers and electron-rich aromatics and heteroaromatics.5
Herein, we report on novel Mo(IV) complexes, which
catalyze the C-C and C-N bond-forming allylic substi-
tution of allylic alcohols (rather than acetates) with
Sch em e 2
While complex A proved to be practically inert under
the conditions previously employed by us for Mo(II)
complexes (vide supra), we envisaged that replacing its
* To whom correspondence should be addressed. E-mail: PK10@
Le.ac.uk.
-
chlorides by weakly coordinating ligands, such as CF3SO3
† University of Leicester.
or SbF6-, could provide a reactive catalyst.8 Indeed, the
two complexes B and C, generated in situ from A on
reaction with stoichiometric amounts of TfOAg and
‡ GlaxoWellcome.
(1) For overviews of Pd(0)-catalyzed allylic substitution, see: (a)
Trost, B. M. Acc. Chem. Res. 1980, 13, 385. (b) Tsuji, J . Tetrahedron
1986, 42, 4361. (c) Frost, C. G.; Howarth, J .; Williams, J . M. J .
Tetrahedron: Asymmetry 1992, 3, 1089. (d) Trost, B. M.; Van Vranken,
D. L. Chem. Rev. 1996, 96, 395. (e) Trost, B. M. Acc. Chem. Res. 1996,
29, 355. (f) Ba¨ckvall, J .-E. Acta Chem. Scand. 1996, 50, 661. See also
the reference section in: (g) Stary´, I.; Zaj´ıcˇek, J .; Kocˇovsky´, P.
Tetrahedron 1992, 48, 7229.
(2) Trost, B. M.; Lautens, M. J . Am. Chem. Soc. 1982, 104, 5543.
(b) Trost, B. M.; Merlic, C. A. J . Am. Chem. Soc. 1990, 112, 9590. (c)
Dvorˇa´k, D.; Stary´, I.; Kocˇovsky´, P. J . Am. Chem. Soc. 1995, 117, 6130.
(d) Trost, B. M.; Hachiya, I. J . Am. Chem. Soc. 1998, 120, 1104.
(3) (a) Trost, B. M.; Hung, M.-H. J . Am. Chem. Soc. 1983, 105, 7757.
(b) Trost, B. M.; Hung, M.-H. J . Am. Chem. Soc. 1984, 106, 6837. (c)
Lloyd-J ones, G. C.; Pfaltz, A. Angew. Chem., Int. Ed. Engl. 1995, 34,
462. (d) Lloyd-J ones, G. C.; Pfaltz, A. Z. Naturforsch. B 1995, 50b, 361.
(e) Lehmann, J .; Lloyd-J ones, G. C. Tetrahedron 1995, 51, 8863. (f)
Frisell, H.; Åkermark, B. Organometallics 1995, 14, 561.
(4) (a) Bergbreiter, D. E.; Weatherford, D. A. J . Chem. Soc., Chem.
Commun. 1989, 833. (b) Stary´, I.; Stara´, I. G.; Kocˇovsky´, P. Tetrahedron
1994, 50, 529. For a recent discussion of stoichiometric substitution
of rhenium complexes of allylic alcohols, see: (c) Legoupy, S.; Cre´visy,
C.; Guillemin, J .-C.; Gre´e, R.; Toupet, L. Chem.sEur. J . 1998, 4, 2162
and refs cited therein.
(5) (a) Dvorˇa´kova´, H.; Dvorˇa´k, D.; Sˇrogl, J .; Kocˇovsky´, P. Tetrahe-
dron Lett. 1995, 36, 6351. (b) Abbott, A. P.; Malkov, A. V.; Zimmer-
mann, N.; Raynor, J . B.; Ahmed, G.; Steele, J .; Kocˇovsky´, P. Organo-
metallics 1997, 16, 3690. (c) Malkov, A. V.; Baxendale, I. R.; Mansfield,
D. J .; Kocˇovsky´, P. Tetrahedron Lett. 1997, 38, 4895. (d) Malkov, A.
V.; Davis, S. L.; Mitchell, W. L.; Kocˇovsky´, P. Tetrahedron Lett. 1997,
38, 4899. (e) Malkov, A. V.; Baxendale, I. R.; Mansfield, D. J .; Kocˇovsky´,
P. J . Org. Chem. 1999, 64, 2737. (f) Malkov, A. V.; Davis, S. L.;
Baxendale, I. R.; Mitchell, W. L.; Kocˇovsky´, P. J . Org. Chem. 1999,
64, 2751. (g) Kocˇovsky´, P.; Ahmed, G.; Sˇrogl, J .; Malkov, A. V.; Steele,
J . J . Org. Chem. 1999, 64, 2765.
(6) (a) Doyle, G. Inorg. Chem. 1971, 10, 2348. (b) van den Bergen,
A.; Murray, K. S.; West, B. O. Aust. J . Chem. 1972, 25, 705.
(7) This redox reaction is not unusual. Thus, for instance, (acac)2VO
is prepared from V2O5 in a similar manner: Rowe, R. A.; J ones, M. M.
Inorg. Chem. 1966, 5, 114.
(8) For weakly coordinating ligands, see, e.g.: (a) Van Seggen, D.
M.; Hurlburt, P. K.; Anderson, O. P.; Strauss, S. H. Inorg. Chem. 1995,
34, 3453 and refs cited therein. (b) Marks, T. J . Acc. Chem. Res. 1992,
25, 57. (c) Strauss, S. H. Chem. Rev. 1993, 93, 927.
10.1021/jo990372u CCC: $18.00 © 1999 American Chemical Society
Published on Web 06/10/1999

Notes
J . Org. Chem., Vol. 64, No. 14, 1999 5309
Sch em e 3
Sch em e 4
AgSbF6, respectively, proved to react with allylic acetates
though the main products corresponded to elimination.9
Therefore, we focused on allylic alcohols as substrates.
Ca r bon Nu cleop h iles. Initially, no reaction was
observed between cinnamyl alcohol 4 and the silyl enol
ether derived from acetophenone in the presence of either
B or C. In this case, the failure was mainly due to the
preferential decomposition of the silyl enol ether to the
parent ketone, which is faster than the desired reaction.10
By contrast, the reaction of 4 with phenol occurred at
room temperature (with 2 mol % of C), affording p-
cinnamyl phenol (6; 58%) as the main product in 15 min
(Scheme 3). Similarly, the homologous alcohol 5 gave the
expected para-substituted products 7 (79%) and 8 (90%)
on reaction with phenol and anisole, respectively, which
parallels the results obtained5 with Mo(II) catalysts.11
With Mo(II) catalysts, we have previously observed
that allylations of phenol and anisole with acyclic allylic
acetates (e.g., cinnamyl acetate) tend to preferentially
occur in the para position;5 when the para position was
blocked, as in the case of p-cresol 11, ortho-substituted
products were formed exclusively.5 Moreover, after pro-
longed reaction times, electrophilic cyclization of the
resulting olefinic phenol was observed in those cases
where protonation of the allylic bond could generate a
tertiary carbocation. Therefore, it was desirable to com-
pare the reactivity of Mo(II) catalysts with that of the
new Mo(IV) complexes. To this end, a mixture of prenyl
alcohol 9 and p-cresol was treated with complex C (2 mol
%) at room temperature (Scheme 4). Monitoring of the
reaction indicated the disappearance of the starting
materials and a gradual conversion of the initially formed
product (presumably 12) to the chromane derivative 13;
after 24 h at ambient temperature, 13 was isolated in
28% yield.12 The tertiary alcohol 10 proved to be a better
choice as it gave a much cleaner reaction, producing 13
in 46% yield, contaminated by the “open” o-allyl inter-
mediate 12 (∼5%). Hence, the present Mo(IV) catalyst
followed the same reaction course as, and proved to be
superior to, its Mo(II) counterpart as it is giving higher
conversion and a cleaner product.
The reaction of linalool (14) with anisole was found to
be less efficient, giving the expected5 para-substituted
product 15 in 30% yield (Scheme 4). On the other hand,
geraniol and nerol (trans- and cis-allylic isomers of
linalool) gave mainly elimination/polymerization prod-
ucts. In contrast to Mo(II) complexes,5 other allylic
substrates, such as isophorol, also turned out to undergo
elimination. As catalysts for C-C bond formations,
therefore, these Mo(IV) complexes appear to be in part
complementary to their Mo(II) congeners.5
Nitr ogen Nu cleop h iles. To investigate further the
reactivity and scope of the new Mo(IV) catalysts, we have
focused on C-N bond formation, where Mo(0) and Mo-
(II) complexes proved inefficient.5 However, numerous
initial experiments with a variety of allylic alcohols and
acetates and primary or secondary amines and sodium
azide were unsuccessful.13 Finally, we found trimethyl-
silyl azide14 to react with cinnamyl alcohol (4) in the
presence of complex B (5 mol %) at ambient temperature
in 10 min, affording cinnamyl azide 16 in 65% isolated
yield (Scheme 5). Under the same conditions, homologous
alcohol 5 produced azide 17 (30%).
Cinnamyl azide 16 was also formed from isocinnamyl
alcohol 18 (57%), indicating that a common intermediate
was generated from both 4 and 18. Similarly, allylic
alcohol 10 gave prenyl azide 19 (20%),15 demonstrating
that the intermediate is trapped by azide selectively at
the less substituted terminus, a regioselectivity analo-
gous to attack of oxygen nucleophiles in the presence of
Mo(II) catalysts.5,16 In contrast to the ready reaction of
10, prenyl alcohol 9 reacted sluggishly, demonstrating
the importance of the first ionizing step. The alicylic
alcohols 20, 21, and 24 also produced the respective
azides 22 (61%), 23 (89%), and 25 (54%).
(9) The only notable exception in several unsuccessful attempts was
the reaction of 2-cyclohexen-1-yl acetate with phenol in the presence
of C (2 mol %) in CH2Cl2, which gave a 1:1 mixture of o- and p-(2-
cyclohexen-1-yl)phenols (75%) at ambient temperature in 30 min.
(10) Note that in the presence of Mo(II) catalysts, such as [Mo-
(CO)4Br2]2, the analogous reaction with cinnamyl acetate is straight-
forward, giving the corresponding product at room temperature.5e
(11) Interestingly, while practically inert in other reactions, complex
A (5 mol %) was found to catalyze the reaction of 5 with PhOH in
CH2Cl2 (at rt, 24 h) to give products of O-allylation (rather than
C-allylation), namely 1-phenyl-3-phenoxy-1-butene (33%) and di(1-
phenyl-1-buten-3-yl) ether (30%). With 5 mol % of (acac)2Mo(O2CCF3)2,
generated in situ from A and CF3CO2Ag (2 equiv), the same mixture
(∼1:1) was obtained in 70% yield. Another C-O bond-forming reaction
was observed between (R)-(+)-1-phenyl-1-buten-3-yl acetate and MeOH
in the presence of C (5 mol %) in CH2Cl2 (rt, 1 h), which gave (()-3-
methoxy-1-phenyl-1-butene.
To investigate the stereochemistry of this C-N bond-
forming reaction, epimeric steroidal alcohols 26 and 27
were employed as probes (Scheme 6). Both these alcohols
(13) The failure in these cases is apparently due to the preferential
coordination of the catalyst to the amine or N3-, which renders Mo-
(IV) unreactive.
(14) For the use of Me3SiNe3 in the Pd(0)-catalyzed allylic substitu-
tion, see: Trost, B. M.; Cook, G. R. Tetrahedron Lett. 1996, 37, 7485.
(15) In this case, the relatively low isolated yield is due to the high
volatility of the product.
(16) Note that treatment of 10 with HBr is a preparative method
to make prenyl bromide: Tietze, L.-F.; Eicher, T. Reaktionen und
Synthesen im organisch-chemischen Praktikum; G. Thieme: Stuttgart,
1981; p 42.
(12) The yield is based on 9 and is rather low in this case owing to
the competing elimination and polymerization. More than 60% of the
unreacted 11 has been detected in the crude reaction mixture.

5310 J . Org. Chem., Vol. 64, No. 14, 1999
Notes
Sch em e 5
Con clu sion s
We have designed novel Mo(IV) complexes B and C
that catalyze C-C bond-forming reactions of allylic
alcohols with electron-rich aromatics (e.g., 4 f 6) and
C-N bond-forming reactions with Me3SiN3 (e.g., 4 f 16
r 18) under mild conditions. Since the Mo(II) complexes,
described by us earlier (vide supra),5 failed to form C-N
bonds, it can be concluded that the new Mo(IV) catalysts
B and C are complementary to Mo(II). All these catalysts
act as mild and selective Lewis acids. Ongoing prelimi-
nary experiments suggest that both Mo(II) and Mo(IV)
complexes could become very useful in carbonyl ene
cyclizations5g and other Lewis acid-catalyzed reactions
and introduce new, interesting features to this area.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points were determined on a
Kofler block and are uncorrected. The NMR spectra were
recorded in CDCl3, 1H at 250 MHz and 13C at 62.9 MHz with
1
chloroform-d1 (δ 7.26, H; δ 77.0, 13C) as internal standard; 2D-
techniques were used to establish the structures and to assign
the signals. The IR spectra were recorded for a thin film between
KBr plates unless otherwise stated. The mass spectra (EI and/
or CI) were measured on a dual sector mass spectrometer using
direct inlet and the lowest temperature enabling evaporation.
The GC-MS analysis was performed with an RSL-150 column
(25m × 0.25 mm). All reactions were performed under an
atmosphere of dry, oxygen-free nitrogen in oven-dried glassware.
Solvents and solutions were transferred by syringe-septum and
cannula techniques. All reagents were purchased at highest
commercial quality and used without further purification, unless
otherwise stated. Yields are given for isolated product showing
one spot on a TLC plate and no impurities detectable in the NMR
spectrum. The identity of the products prepared by different
methods was checked by comparison of their NMR, IR, and MS
data and by the TLC behavior. Most of the products are known
compounds.18,19 Complex A was prepared following the procedure
reported in ref 6b.
a
Key: (a) Me3SiN3, (acac)2Mo(OTf)2 (5 mol %), CH2Cl2, rt, 10
min.
Sch em e 6
Gen er a l P r oced u r e for th e Allylic Su bstitu tion Rea c-
t ion s Ca t a lyzed b y Com p lex C a n d w it h E lect r on -R ich
(18) 6: (a) Wenkert, E.; Fernandes, J . B.; Michelott, E. L.; Swindell,
C. S. Synthesis 1983, 701. (b) Dewar, M. J . S.; Nahlovsky, B. D. J .
Am. Chem. Soc. 1974, 96, 460. 7 and 8: Reference 5f. 12: (c) Bunina-
Krivorukova, L. I.; Feoktistov, V. M.; Aleksandrova, E. K.; Bal’yan,
Kh. V. Zh. Org. Khim. 1982, 18, 859. (d) J ulia, M.; Nel, M.; Uguen, D.
Bull. Soc. Chim. Fr. 1987, 487. (e) De Renzi, A.; Panunzi, A.; Saporito,
A.; Vitagliano, A. J . Chem. Soc., Perkin Trans. 2 1983, 993. 13:
Reference 18c,d. (h) Baird, K. J .; Grundon, M. F. J . Chem. Soc., Perkin
Trans. 1 1980, 1820. 15: (f) Ballester, P.; Capo, M.; Saa, J . M.
Tetrahedron Lett. 1990, 31, 1339. (g) Araki, S.; Manabe, S.; Butsugan,
Y. Chem. Lett. 1982, 797.
(19) 16 (E): (a) Manhart, E.; von Werner, K. Synthesis 1978, 705.
(b) Hassner, A.; Fibiger, R.; Andisik, D. J . Org. Chem. 1984, 49, 4237.
(c) Murahashi, S.; Taniguchi, Y.; Imada, Y.; Tanigawa, Y. J . Org. Chem.
1989, 54, 3292. (d) Viaud, M. C.; Rollin, P. Synthesis 1990, 130. (e)
Kanai, T.; Kanagawa, Y.; Ishii, Y. J . Org. Chem. 1990, 55, 3274. (f)
Hung, R. R.; Straub, J . A.; Whitesides, G. M. J . Org. Chem. 1991, 56,
3849. (g) Blart, E.; Genet, J .-P.; Safi, M.; Savignac, M.; Sinou, D.
Tetrahedron 1994, 50, 505. (h) Alvarez, S. G.; Alvarez, M. T. Synthesis
1997, 413. (i) Rosen, T.; Lico, I. M.; Chu, D. T. W. J . Org. Chem. 1988,
53, 1580. 16 (E/ Z): (j) Balderman, D.; Kalir, A. Synthesis 1978, 24.
(k) Yang, C.-H.; Shen, H.-J . Tetrahedron Lett. 1993, 34, 4051. (l)
Koziara, A.; Zwierzak, A. Synthesis 1992, 1063. 17 (E): (m) Murahashi,
S.; Taniguchi, Y.; Imada, Y.; Tanigawa, Y. J . Org. Chem. 1989, 54,
3292. 19: (n) Kanai, T.; Kanagawa, Y.; Ishii, Y. J . Org. Chem. 1990,
55, 3274. (o) Banert, K.; Groth, S. Angew. Chem. 1992, 104, 865. 22:
(p) Mizuno, M.; Shioiri, T. Chem. Commun. 1997, 2165. (q) Breton, G.
W.; Daus, K. A.; Kropp, P. J . J . Org. Chem. 1992, 57, 6646. 23: (r)
Grieco, P. A.; DuBay, W. J .; Todd, L. J . Tetrahedron Lett. 1996, 37,
8707. (s) Grieco, P. A.; Handy, S. T. Tetrahedron Lett. 1997, 38, 2645.
25: (t) Hassner, A.; Fowler, F. W. J . Org. Chem. 1968, 33, 2684. (u)
Blond, A.; Platzer, N.; Guy, A.; Dhotel, H.; Serva, L. Bull. Soc. Chim.
Fr. 1996, 133, 283. (v) Chmielowiec, U.; Uzarewicz, I.; Uzarewicz, A.
Pol. J . Chem. 1990, 64, 613. (x) Hassner; Fowler, F. J . Org. Chem.
1968, 33, 2684, 2686. 28: Reference 17. 29: Reference 17. (y) Loibner,
H.; Zbiral, E. Helv. Chim. Acta 1976, 59, 2100.
turned out to produce a mixture of 3â- and 3R-azides 28
and 29 (rt, 10 min), in which the 3R-azide 29 predomi-
nated. Thus, starting from 26, a 15:85 mixture of 28 and
29 was obtained (80%), whereas 27 afforded a 30:70
mixture (75%). This behavior again demonstrates the
existence of a common intermediate that is preferentially
attacked from the axial side, presumably owing to the
stereoelectronic effect that dictates an axial attack;17 the
slight imbalance in the product distribution indicates a
nonideal SN1 mechanism.
The latter results parallel those obtained with Mo(II)
catalysts for C-C bond formation;5 all the data ac-
cumulated to date clearly indicate that, rather than
generating η3-complexes, both Mo(II)5 and Mo(IV) cata-
lysts act as mild Lewis acids with noncoordinated allylic
cations as intermediates. This behavior is in sharp
contrast to Mo(0)2 catalysts that are known to react via
intermediate η3 complexes (Scheme 1).
(17) The configuration at the 3-position of 28 and 29 was determined
from the signal of 4-H in the 1H NMR spectra: while 3â-substituted
derivatives consistently exhibit this signal as a broad singlet, the 3R
epimers are characterized by a broad doublet with J ≈ 5 Hz. The 28:
29 ratio was determined by integration of the 4-H signals in the 1H
NMR spectrum of the crude mixture. For further details, see: Ortar,
G.; Paradisi, M. P.; Morera, E.; Romeo, A. J . Chem. Soc., Perkin Trans.
1 1978, 4.

Notes
J . Org. Chem., Vol. 64, No. 14, 1999 5311
Ar om a tics a s Nu cleop h iles. (acac)2MoCl2 complex6b (10 mg,
0.027 mmol, 2.7 mol %) was added to a stirred solution of the
allylic substrate (1 mmol) and an electron-rich aromatic nucleo-
phile (1.3 mmol) in CH2Cl2 (5 mL) at room temperature, followed
by addition of solid silver hexafluoroantimonate (10 mg, 0.029
mmol). The mixture was stirred under nitrogen at room tem-
perature for 10-30 min and then diluted with ether (20 mL),
and the ethereal solution was washed successively with 5%
aqueous NaHCO3 and water and dried with MgSO4. The solvent
was evaporated under reduced pressure to give a crude product,
which was purified by flash chromatography on a silica gel
column. For details and the yields see the text.
gel (90 g) with an 80:20 petroleum ether-ether mixture or a
90:10 hexanes-ethyl acetate mixture. For details and the yields
see the text.
(E)-3-Azid o-1-p h en yl-1-p r op en e 16.19a-i Obtained as a pale
yellow oil (65% from 5; 57% from 18). 16: 1H NMR δ 3.92 (2 H,
d, J ) 6.6 Hz, CH2N3), 6.22 (dt, J ) 15.7, 6.6 Hz, 1 H, CHd
CHCH2), 6.63 (d, J ) 15.7 Hz, 1 H, PhCHdH), 7.22-7.43 (m, 5
H, arom); 13C NMR δ 53.1 (t), 122.4 (d), 126.7 (d), 128.2 (d), 128.7
(d), 134.6 (s); IR ν(N3) 2094 cm-1; MS (EI) m/z 159 (M+•, 19),
117 (M+ - N3, 100).
(E)-3-Azid o-1-p h en yl-1-bu ten e 17.19c,m Obtained from 5 as
a pale yellow oil (30%). 17: 1H NMR δ 1.35 (3 H, d, J ) 7.0 Hz,
CH3), 4.10 (1 H, m), 6.09 (dd, J ) 6.6 and 16.1 Hz, 1 H, PhCHd
CH), 6.60 (d, J ) 16.1 Hz, 1 H, PhCHdH), 7.05-7.55 (m, 5 H,
arom); 13C NMR δ 20.6 (q), 60.1 (d), 127.1 (d), 128.5 (d), 128.8
1-P h en yl-3-(4′′-h yd r oxyp h en yl)-1-p r op en e (6).18a,b Ob-
tained from 4 and PhOH as a colorless oil (58%). 6: 1H NMR δ
3.46 (d, J ) 6.0 Hz, 2 H, 3-H), 5.01 (s, 1 H, OH), 6.31 (dt, J )
15.9, 6.0 Hz, 1 H, 2-H), 6.42 (d, J ) 16.0 Hz, 1 H, 1-H), 6.84 (d,
J ) 8.5 Hz, 2 H, 3′′-H, 5′′-H), 7.13 (d, J ) 8.5 Hz, 2 H, 2′′-H,
6′′-H), 7.17-7.35 (m, 5 H, arom); 13C NMR δ 38.9 (3-CH2), 115.8
(3′′,5′′-CH), 126.6 (CH), 127.5 (CH), 129.0 (CH), 130.1 (CH), 130.3
(CH), 131.2 (1-CH), 132.8 and 138.0 (1′-C and 1′′-C), 154.3 (4′′-
C); MS (EI) m/z 210 (100, M•+).
(d), 129.1 (d), 132.6 (d), 136.5 (s); IR ν(N3) 2094 cm-1
.
1-Azid o-3-m eth ylbu t-2-en e 19.19e,n,o Obtained as from 10 a
pale yellow oil (20%): 1H NMR δ 1.72 (s, 3 H). 1.81 (s, 3 H),
3.75 (d, J ) 7.5 Hz, 2 H) 5.34 (t, J ) 7.0 Hz, 1 H); IR ν(N3) 2100
cm-1
.
1-Azid ocycloh ex-2-en e 22.19p,q Obtained from 20 as a pale
yellow oil (61%). 22: 1H NMR δ 1.74 (m, 4 H), 2.11 (m, 2 H),
3.85 (br m, 1 H, CHN3), 5.69 (ddt, J ) 2.2, 3.9 and 10 Hz, 1 H,
N3CHCHdCH), 6.01 (ddt, J ) 1.5, 3.9, 10 Hz, 1 H, N3CHCHd
1-P h en yl-3-(4′′-h yd r oxyp h en yl)-1-bu ten e (7).5f Obtained
from 4 and PhOMe as a colorless oil (79%). 7: 1H NMR δ 1.41
(d, J ) 6.9 Hz, 3 H, Me), 3.56 (m, 1 H, 3-H), 5.08 (brs, 1 H, OH),
6.36 (m, 2 H, 1-H, 2-H), 6.75 (d, J ) 8.5 Hz, 2 H, 3′′-H, 5′′-H),
7.11 (d, J ) 8.5 Hz, 2 H, 2′′-H, 6′′-H), 7.17-7.36 (m, 5 H, arom);
13C NMR δ 21.8 (Me), 42.1 (3-CH), 115.8 (3′′,5′′-CH), 126.6 (CH),
127.5 CH), 128.8 (CH), 129.0 (CH), 130.2 (CH), 136.1 (1-CH),
138.1 and 138.3 (1′, 1′′-C), 154.3 (4′′-C); MS (EI) m/z 224 (73,
CH); IR ν(N3) 2100 cm-1
.
1-Azid o-3,5,5-tr im eth ylcycloh ex-2-en e 23.19r,s Obtained
from 21 as a pale yellow oil (89%). 23: 1H NMR δ 0.89 (s, 3 H),
1.01 (s, 2 H), 1.26-1.38 (m, 1 H), 1.60-1.92 (m, 1 H), 1.70 (s, 6
H), 3.90 (br m, 1 H), 5.38 (d, J ) 0.93 Hz, 1 H); 13C NMR δ 24.0
(q), 26.2 (q), 31.0 (s), 31.3 (q), 41.1 (t), 44.2 (t), 57.6 (d), 118.9
(d), 138.8 (s); IR ν(N3) 2100 cm-1; MS (CI) m/z 166 (M+•, 6), 138
(M•+ + H - N2, 14), 123 (M+ - N3, 100).
M
•+), 209 (100).
1-P h en yl-3-(4′′-m eth oxyp h en yl)-1-bu ten e (8).5f Obtained
from 5 and PhOMe as a colorless oil (90%). 8: 1H NMR δ 1.43
(d, J ) 6.9 Hz, 3 H, Me), 3.58 (m, 1 H, 3-H), 3.76 (s, 3 H, OMe),
6.37 (m, 2 H, 1-H, 2-H), 6.85 (d, J ) 8.8 Hz, 2 H, 3′′-H, 5′′-H),
7.17 (d, J ) 8.8 Hz, 2 H, 2′′-H, 6′′-H), 7.20-7.36 (m, 5 H, arom);
13C NMR δ 21.3 (Me), 41.7 (3-CH), 55.2 (OMe), 113.8 (3′′,5′′-
CH), 126.1 (CH), 127.0 (CH), 128.2 (CH), 128.3 (CH), 128.5 (CH),
135.6 (1-CH), 137.6 and 137.7 (1′-C and 1′′-C), 158.0 (4′′-C); MS
(EI) m/z 238 (71, M•+), 223 (100).
1-Azid ocyclop en t-2-en e 25.19t-x Obtained from 24 as a pale
yellow oil (54%). 25: 1H NMR δ 1.40-2.62 (m, 4 H), 3.91-4.53
(m, 1 H, CHN3), 5.63-6.18 (m, 2 H); IR ν(N3) 2100 cm-1
.
3â-Azid o-ch olest-4-en e (28) a n d 3r-Azid o-ch olest-4-en e
(29). (acac)2MoCl2 complex6b (5 mg, 0.014 mmol, 3.6 mol %) was
added to a solution of cholest-4-en-3â-ol (26) (150 mg, 0.39 mmol)
and trimethylsilyl azide (54 mg, 0.47 mmol, 1.2 equiv) in dry
CH2Cl2 (10 mL), followed by addition of silver triflate (10 mg,
0.039 mmol, 10 mol %), and the mixture was stirred at room
temperature for 10 min. The volume of the solvent was then
reduced to ∼1/5 by evaporation in vacuo at 20 °C, and the residue
was chromatographed on a column of silica gel (90 g) with an
80:20 petroleum ether-ether mixture to afford a 15:85 mixture
of 2817 and 2917 (128 mg, 80%) as a colorless oil. 28: 1H NMR
(measured in a mixture with the 3R-isomer) δ 0.68 (s, 3 H, 18-
H), 1.05 (s, 3 H, 19-H), 3.80 (m, W ) 19.5 Hz, 1 H, 3R-H), 5.24
(br s, 1 H, 4-H), in accordance with the literature.17 29: 1H NMR
(measured in a mixture with the 3â isomer) δ 0.70 (s, 3 H, 18-
H), 0.95 (s, 3 H, 19-H), 3.84 (m, W = 28 Hz, 1 H, 3â-H), 5.38 (br
d, J ) 3.5 Hz, 1 H, 4-H), in accordance with the literature.17,19y
3,4-Dih yd r o-2,2-d im eth yl-2H-ben zop yr a n (13).18c-e Ob-
tained as a colorless oil (28% from 9 + 11; 46% from 10 + 11).
13: 1H NMR δ 1.33 (s, 6 H, 2 × 2-CH3), 1.80 (m, 2 H, 3-H), 2.77
(t, J ) 6.9 Hz, 2 H, 4-H), 6.71-7.11 (m, 4 H, arom); 13C NMR δ
22.9 (3-CH2), 27.3 (2 × 2-Me), 33.2 (4-CH2), 74.5 (2-C), 117.7
and 120.0 (6- and 8-CH), 121.3 (4a-C), 127.7 and 129.8 (5- and
7-CH), 154.4 (8a-C).
1-(4′-Meth oxyp h en yl)-3,7-d im eth yl-2,6-octa d ien e (15).18f,g
Obtained from 14 and PhOMe as a colorless oil (30%). 15: 1H
NMR δ 1.61 (s, 3 H, 3-Me), 1.71 (s, 6 H, 7,8-Me), 1.90-2.21 (m,
4 H, 4,5-H), 3.29 (m, 2 H, 1-H), 3.79 (s, 3 H, OMe), 5.11 (m, 1 H,
6-H), 5.33 (m, 1 H, 2-H), 6.83 (d, J ) 8.8 Hz, 2 H, 3′-H, 5′-H),
7.09 (d, J ) 8.8 Hz, 2 H, 2′-H, 6′-H).
Gen er a l P r oced u r e for th e Allylic Su bstitu tion Rea c-
t ion s Ca t a lyzed b y Com p lex B a n d w it h Tr im et h ylsilyl
Azid e a s Nu cleop h ile. (acac)2MoCl2 complex6b (5 mg, 0.014
mmol, 1.9 mol %) was added to a stirred solution of allylic alcohol
(0.75 mmol) and trimethylsilyl azide (103 mg, 0.90 mmol, 1.2
equiv) in dry CH2Cl2 (10 mL), followed by addition of solid silver
triflate (10 mg, 0.039 mmol, 5.2 mol %), and the mixture was
stirred at room temperature for 10 min. The volume of the
solvent was then reduced to ∼1/5 by evaporation in vacuo at 20
°C, and the residue was chromatographed on a column of silica
Ack n ow led gm en t. We thank the EPSRC for Grant
Nos. GR/H 92067, GR/K07140, and GR/L41448 and
EPSRC and GlaxoWellcome for a CASE award to P.S.
Su p p or tin g In for m a tion Ava ila ble: MS and HRMS data
for the compounds described. This material is available free
of charge via the Internet at http://pubs.acs.org.
J O990372U