Synthesis of allenes from allylic alcohol derivatives bearing a bromine atom using a palladium(0)/diethylzinc system

Article abstract of DOI:10.1021/jo016320y

A general and efficient synthesis of allenes using a palladium(0)/diethylzinc system is described. Treatment of mesylates or trichloroacetates of (E)- or (Z)-2-bromoalk-2-en-1-ols with diethylzinc in the presence of a catalytic amount of palladium(0) affords allenes bearing an aminoalkyl, alkyl, or aryl substituent(s) in good to high yields. No transfer of chirality from the stereogenic center carrying the mesyloxy group to the allene was observed.

Full text of DOI:10.1021/jo016320y

J . Org. Chem. 2002, 67, 1359-1367
1359
Syn th esis of Allen es fr om Allylic Alcoh ol Der iva tives Bea r in g a
Br om in e Atom Usin g a P a lla d iu m (0)/Dieth ylzin c System
Hiroaki Ohno, Kumiko Miyamura, and Tetsuaki Tanaka*
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamadaoka, Suita,
Osaka 565-0871, J apan
Shinya Oishi, Ayako Toda, Yoshiji Takemoto, Nobutaka Fujii, and Toshiro Ibuka†
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto 606-8501, J apan
t-tanaka@phs.osaka-u.ac.jp
Received November 27, 2001
A general and efficient synthesis of allenes using a palladium(0)/diethylzinc system is described.
Treatment of mesylates or trichloroacetates of (E)- or (Z)-2-bromoalk-2-en-1-ols with diethylzinc
in the presence of a catalytic amount of palladium(0) affords allenes bearing an aminoalkyl, alkyl,
or aryl substituent(s) in good to high yields. No transfer of chirality from the stereogenic center
carrying the mesyloxy group to the allene was observed.
In tr od u ction
nation reaction in the presence of tributylphosphine to
yield the allene 5, only in a single example (eq 2).5a,b
Semmelhack and his associate observed formation of a
monosubstituted allene 7 as an undesired product by
treatment of an allylic mesylate 6 with 2.4 equiv of Ni-
(PPh3)2(CO)2, also in one example.5c However, no system-
atic investigation involving the synthesis of allenes from
such class of compounds has been carried out, and a
catalytic synthesis of allenes7 from such substrates is
unknown as far as we are aware.
Allenes are an important class of molecules with high
chemical reactivity, due to their cumulated double bonds.1
Owing to the recent development of synthesis and transi-
tion metal-catalyzed reactions of allenes,1e,1f,2 they have
become more versatile intermediates in organic synthesis.
Among various substituted allenes, amino allenes have
attracted considerable interest in recent years, since they
are versatile substrates for constructing various aza-
cycles.2
In the course of our study involving synthesis of
ethynylaziridines,3 we found that the allylic mesylate 1
can be converted into the amino allene 2 on treatment
with diethylzinc in the presence of palladium(0) catalyst
(eq 1).4 Scanning the literature revealed that there have
been some reports describing related synthesis of al-
lenes.5,6 In 1973, Lukas and co-workers reported that
2-chloro-1,3-diene 3 and palladium(II) chloride forms an
allylpalladium(II) complex 4, which undergoes an elimi-
† Deceased J anuary 20, 2000.
(1) For reviews, see: (a) Brandsma, L.; Verkruijsse, H. D. In
Synthesis of Acetylenes, Allenes and Cumulenes; Elsevier: New York,
1981. (b) Smadja, W. Chem. Rev. 1983, 83, 263. (c) Pasto, D. J .
Tetrahedron 1984, 40, 2805. (d) Marshall, J . A. Chem. Rev. 2000, 100,
3163. (e) Yamamoto, Y.; Radhakrishnan, U. Chem. Soc. Rev. 1999, 28,
199. (f) Zimmer, R.; Dinesh, C. U.; Nandanan, E.; Khan, F. A. Chem.
Rev. 2000, 100, 3067. (g) Hashmi, A. S. K. Angew. Chem., Int. Ed. 2000,
39, 3590.
(2) (a) Ohno, H.; Toda, A.; Miwa, Y.; Taga, T.; Osawa, E.; Yamaoka,
Y.; Fujii, N.; Ibuka, T. J . Org. Chem. 1999, 64, 2992. (b) Ohno, H.;
Anzai, M.; Toda, A.; Ohishi, S.; Fujii, N.; Tanaka, T.; Takemoto, Y.;
Ibuka, T. J . Org. Chem. 2001, 66, 4904, and references sited therein.
(3) (a) Ohno, H.; Toda, A.; Fujii, N.; Ibuka, T. Tetrahedron: Asym-
metry 1998, 9, 3929. (b) Ohno, H.; Toda, A.; Takemoto, Y.; Fujii, N.;
Ibuka, T. J . Chem. Soc., Perkin Trans. 1 1999, 2949.
Recently, we have reported that internal allenes (1,3-
disubstituted allenes) bearing an N-protected amino
group could be readily synthesized from ethynylaziridines
by treatment with organocopper reagents;8 however,
(4) A portion of this study was reported in a preliminary com-
munication: Ohno, H.; Toda, A.; Oishi, S.; Tanaka, T.; Takemoto, Y.;
Fujii, N.; Ibuka, T. Tetrahedron Lett. 2000, 41, 5131.
(6) Reverse reactions of our allene synthesis have been reported.
For formation of π-allylpalladium(II) complexes by the reaction of
allenes with a stoichiometric amount of Pd(II), see: (a) Lupin, M. S.;
Shaw, B. L. Tetrahedron Lett. 1964, 5, 883. (b) Schultz, R. G.
Tetrahedron 1964, 20, 2809, and see also, ref 5b. Ba¨ckvall and
co-workers reported the palladium(II)-catalyzed 1,2-oxidation of a
certain allene with p-benzoquinone in the presence of LiBr affording,
only in an isolated example, 2,3-dibromoprop-1-ene derivative, see: (c)
J onasson, C.; Karstens, W. F. J .; Hiemstra, H.; Ba¨ckvall, J .-E.
Tetrahedron Lett. 2000, 41, 1619. See also, (d) J onasson, C.; Horva´th,
A.; Ba¨ckvall, J .-E. J . Am. Chem. Soc. 2000, 122, 9600.
(5) (a) Lukas, J .; Visser, J . P.; Kouwenhoven, A. P. J . Organomet.
Chem. 1973, 50, 349. See also, (b) Lupin, M. S.; Powell, J .; Shaw, B.
L. J . Chem. Soc. A 1966, 1687. (c) Semmelhack, M. F.; Brickner, S. J .
J . Am. Chem. Soc. 1981, 103, 3945. For other related synthesis of
allenes, see: (d) Konoike, T.; Araki, Y. Tetrahedron Lett. 1992, 33, 5093.
(e) Bhuvaneswari, N.; Venkatachalam, C. S.; Balasubramanian, K. K.
J . Chem. Soc., Chem. Commun. 1994, 1177. (f) Gabbutt, C. D.;
Hepworth, J . D.; Heron, B. M.; Rahman, M. M. J . Chem. Soc., Chem.
Commun. 1994, 1733.
10.1021/jo016320y CCC: $22.00 © 2002 American Chemical Society
Published on Web 01/29/2002

1360 J . Org. Chem., Vol. 67, No. 4, 2002
Ohno et al.
Sch em e 1a
preparation of monosubstituted allenes of the type 2
without contaminating the corresponding acetylene by
the use of organocopper chemistry has proven to be quite
difficult. Although reliable synthetic methods of terminal
allenes have been already developed,9-11 some of these
are unsuitable for the synthesis of allenes bearing a
nitrogen functionality.12 The potential utility of the
synthesis of allenes by a palladium(0)/diethylzinc system
(eq 1), especially for the synthesis of amino allenes, led
us to a detailed investigation of this reaction. In this
paper, we present a full account of our investigation into
the synthesis of allenes from esters of 2-bromoalk-2-en-
1-ols using diethylzinc and catalytic palladium(0).4 The
effect of the chirality of the mesyloxy group of the
secondary substrates, on the axial chirality of the result-
ing internal allenes, is also described.
a
Abbreviations: Mts ) 2,4,6-trimethylphenylsulfonyl; Mtr )
4-methoxy-2,3,6-trimethylphenylsulfonyl.
Sch em e 2a
Resu lts a n d Discu ssion
Syn th esis of Ester s of Allylic Alcoh ols Bea r in g a
Br om in e Atom . The requisite mesylates of brominated
(Z)-allylic alcohols 9a -e bearing a protected amino group
were prepared in high yields starting from natural
R-amino acids following the published procedure (Scheme
1).3 The (Z)-mesylates 10a -e were also synthesized via
the same sequence of reactions (see the Supporting
Information).
Mesylates 9f and 10f were synthesized as shown in
Scheme 2. Thus, 3-amino-1-propanol 11 was treated suc-
cessively with p-toluenesulfonyl chloride in the presence
of triethylamine, oxalyl chloride-DMSO-N,N-diisopro-
pylethylamine, and a brominated ylide [Ph3PdC(Br)CO2-
Me]13 to afford a 5:1 mixture of the (Z)- and (E)-R-bromo-
(7) For transition metal-catalyzed synthesis of allenes, see: (a)
Ogoshi, S.; Nishiguchi, S.; Tsutsumi, K.; Kurosawa, H. J . Org. Chem.
1995, 60, 4650. (b) Suginome, M.; Matsumoto, A.; Ito, Y. J . Org. Chem.
1996, 61, 4884. (c) Mikami, K.; Yoshida, A. Angew. Chem., Int. Ed.
1997, 36, 858. (d) Dixneuf, P. H.; Guyot, T.; Ness, M. D.; Roberts, S.
M. Chem. Commun. 1997, 2083. (e) Tsuji, Y.; Taniguchi, M.; Yasuda,
T.; Kawamura, T.; Obora, Y. Org. Lett. 2000, 2, 2635. (f) Ogasawara,
M.; Ikeda, H.; Hayashi, T. Angew. Chem., Int. Ed. 2000, 39, 1042. (g)
Ogasawara, M.; Ikeda, H.; Nagano, T.; Hayashi, T. J . Am. Chem. Soc.
2001, 123, 2089.
(8) (a) Ohno, H.; Toda, A.; Miwa, Y.; Taga, T.; Fujii, N.; Ibuka, T.
Tetrahedron Lett. 1999, 40, 349. (b) Ohno, H.; Toda, A.; Fujii, N.;
Takemoto Y.; Tanaka, T.; Ibuka, T. Tetrahedron 2000, 56, 2811.
(9) (a) Searles, S.; Li, Y.; Nassim, B.; Lopes, M.-T. R.; Tran, P. T.;
Crabbe´, P. J . Chem. Soc., Perkin Trans. 1 1984, 747. (b) Myers, A. G.;
Zheng, B. J . Am. Chem. Soc. 1996, 118, 4492. (c) Dunn, M. J .; J ackson,
R. F. W.; Pietruszka, J .; Turner, D. J . Org. Chem. 1995, 60, 2210.
(10) For recent examples of racemic or achiral allene synthesis,
see: (a) Brummond, K. M.; Dingess, E. A.; Kent, J . L. J . Org. Chem.
1996, 61, 6096. (b) Petasis, N. A.; Hu, Y.-H. J . Org. Chem. 1997, 62,
782. (c) Brody, M. S.; Williams, R. M.; Finn, M. G. J . Am. Chem. Soc.
1997, 119, 3429. (d) Nagaoka, Y.; Tomioka, K. J . Org. Chem. 1998,
63, 6428. (e) Sturla, S. J .; Kablaoui, N. M.; Buchwald, S. L. J . Am.
Chem. Soc. 1999, 121, 1976. (f) Cunico, R. F.; Zaporowski, L. F.; Rogers,
M. J . Org. Chem. 1999, 64, 9307. (g) Delouvrie´, B.; Lacoˆte, E.;
Fensterbank, L.; Malacria, M. Tetrahedron Lett. 1999, 40, 3565. (h)
Varghese, J . P.; Knochel, P.; Marek, I. Org. Lett. 2000, 2, 2849. (i) Tius,
M. A.; Pal, S. K. Tetrahedron Lett. 2001, 42, 2605.
a
Reagents: (a) TsCl, Et3N; (b) (COCl)2, DMSO, CH2Cl2, then
(i-Pr)2NEt; (c) Ph3PdC(Br)CO2Me; (d) DIBAL-H; (e) MsCl, Et3N.
R,â-unsaturated esters 13 and 14 in a good combined
yield, which were separated by flash chromatography.
Reduction of the (Z)-enoate 13 with DIBAL-H yielded the
allylic alcohol 15, which can be readily converted into the
mesylate 9f following the standard procedure. The (E)-
enoate 14 was also converted into the corresponding
mesylate 10f. In a similar manner, the allylic mesylates
(12) For example, (1) when the protected propargylamine 68 was
subjected to the Crabbe´ reaction,9a an intractable mixture of the desired
allene 69 and pyrroline 70 (69:70 ) 8:92) was formed in 35% yield. (2)
Reaction of protected amino alcohol 71 with o-nitrobenzenesulfonyl-
hydrazine (NBSH) under Mitsunobu conditions (Myers’ method9b) gave
a trace amount of the desired allene 72 (<3%), and a considerable
amount of the aziridine 73 (97%) was isolated. (3) Although the reaction
of zinc/copper reagents with propargyl tosylate is a convenient method
for a short synthesis of â-amino allenes,9c yields of some allenes are
considerably low (14-67% in our case).2b
(11) For recent synthesis of enantiomerically enriched allenes, see:
(a) Marshall, J . A.; Pinney, K. G. J . Org. Chem. 1993, 58, 7180. (b)
Nishibayashi, Y.; Singh, J . D.; Fukuzawa, S.; Uemura, S. J . Org. Chem.
1995, 60, 4114. (c) Marshall, J . A.; Wolf, M. A.; Wallace, E. M. J . Org.
Chem. 1997, 62, 367. (d) Naruse, Y.; Watanabe, H.; Ishiyama, Y.;
Yoshida, T. J . Org. Chem. 1997, 62, 3862. (e) Noguchi, Y.; Takiyama,
H.; Katsuki, T. Synlett 1998, 543. (f) Node, M.; Nishide, K.; Fujiwara,
T.; Ichihashi, S. Chem. Commun. 1998, 2363. (g) Satoh, T.; Kuramochi,
Y.; Inoue, Y. Tetrahedron Lett. 1999, 40, 8815. (h) Sweeney, Z. K.;
Salsman, J . L.; Andersen, R. A.; Bergman, R. G. Angew. Chem., Int.
Ed. 2000, 39, 2339. (i) Mikami, K.; Yoshida, A. Tetrahedron 2001, 57,
889. (j) Yamazaki, J .; Watanabe, T.; Tanaka, K. Tetrahedron: Asym-
metry 2001, 12, 669. (k) Schultz-Fademrecht, C.; Wibbeling, B.;
Fro¨hlich, R.; Hoppe, D. Org. Lett. 2001, 3, 1221. See also, refs 7c, 7d,
7g, and 8.

Synthesis of Allenes from Allylic Alcohol Derivatives
J . Org. Chem., Vol. 67, No. 4, 2002 1361
Sch em e 3
Sch em e 4a
9g and 9h were readily prepared from the N-Boc-valinol
1714 and Garner’s aldehyde 18,15 respectively (see the
Supporting Information).
a
Reagents: (a) Ph3PdCHC(O)n-Bu; (b) Br2; (c) Et3N; (d)
DIBAL-H; (e) MsCl, Et3N, DMAP.
Ta ble 1. Syn th esis of Allen e 42a fr om Br om o-m esyla te
9a a
The mesylates (20 and 21) and 23 (Scheme 3) were also
prepared starting from 3-phenylpropanal 19 and the
known alcohol 22,16 respectively, by use of the sequence
of reactions similar to that depicted in Scheme 2. It
should be noted that synthesis of the mesylate derived
from piperonal 24 was quite difficult, presumably due to
the conjugated system.17 Accordingly, the corresponding
acetate 25 and trichloroacetate 26 were prepared instead
of the mesylate. From 1,10-decanediol 27, (Z,Z)- and
(E,Z)-bis(mesylate)s 28 and 29 were prepared in a similar
manner. All the preparative methods and characteriza-
tion for all the intermediates are detailed in the Sup-
porting Information.
Scheme 4 shows preparation of secondary alcohol
derivatives 34, 36-38, 40, and 41, which would be
precursors of internal allenes. Typically, treatment of
n-nonyl aldehyde 30 with Ph3PdCHC(O)n-Bu18 yielded
unsaturated ketone 31, which was brominated by the
reaction with bromine in carbon tetrabromide followed
by dehydrobromination with triethylamine to afford 32
as a single isomer, in 63% yield. Reduction and mesyla-
tion of 32 gave the desired mesylate 34. Since the
mesylate 34 is relatively unstable, crude 34 was used in
the next reaction (Table 3) without further purification.
Although the enone 32 would be also prepared by the
reaction of 30 with bromo-ylide, the bromination-
elimination protocol will be preferred for the synthesis
of brominated enones in which preparation of various
bromo-ylides is unnecessary. Especially, when inexpen-
sive enones are available, this method is quite useful:
entry
catalyst
R2Zn reaction time (min) yieldb (%)
1
2
3
4
5
6
7
8
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4 (1 eq) none
none
Pd(PPh3)4
Pd(OAc)2/4PPh3 Et2Zn
Pd(OAc)2 Et2Zn
Pd(OAc)2/4PBu3 Et2Zn
Et2Zn
none
60
600
20
120
600
60
86
8
82
0
9
85
0
trace
Et2Zn
Me2Zn
600
240
a
All reactions were carried out in THF at room temperature
under argon using 10 mol % of catalyst and 2 equiv of R2Zn.
b
Isolated yields.
chalcone 35 and benzylideneacetone 39 were easily con-
verted into the corresponding esters (36-38, 40, and 41)
in a similar manner (see the Supporting Information).19
Syn th esis of Ter m in a l Allen es Bea r in g a P r o-
tected Am in o Gr ou p . We initiated our study to convert
the mesylate 9a into the allene 42a under various
reaction conditions. The results are summarized in Table
1. Treatment of the mesylate 9a with Pd(PPh3)4 (10 mol
%) and Et2Zn (2 equiv)20 in THF at room temperature
gave the desired allene 42a in 86% yield as the sole
product (entry 1). When the mesylate 9a was treated with
Pd(PPh3)4 (10 mol %) in the absence of Et2Zn, only 8% of
42a was obtained, and 90% of the starting material was
recovered (entry 2). In contrast, reaction of 9a with a
stoichiometric amount of Pd(PPh3)4 in the absence of Et2-
Zn proceeded smoothly to give 82% yield of the allene
(13) (a) Denney, D. B.; Ross, S. T. J . Org. Chem. 1962, 27, 998. (b)
For a recent synthesis of stabilized halo-ylides, see: Kayser, M. M.;
Zhu, J .; Hooper, D. L. Can. J . Chem. 1997, 75, 1315.
(14) Quagliato, D. A.; Andrae, P. M.; Matelan, E. M. J . Org. Chem.
2000, 65, 5037.
(15) Garner, P.; Park, J . M. J . Org. Chem. 1987, 52, 2361.
(16) Bode, J . W.; Doyle, M. P.; Protopopova, M. N.; Zhou, Q.-L. J .
Org. Chem. 1996, 61, 9146.
(17) When the allylic alcohol derived from 24 (precursor of 25 and
26) was subjected to the standard mesylation conditions (MsCl, Et3N,
THF), the corresponding chloride was obtained in 35% yield. Although
this chloride could be prepared in high yield by the reaction of the
same alcohol with thionyl choride, the desired allene could not be
obtained from this chloride by treatment with Pd(0) and Et2Zn.
(18) Such ylides can be easily prepared from Ph3PdCHC(O)Me by
the reaction with LDA and appropriate alkyl halides, see: Cooke, M.
P., J r. J . Org. Chem. 1973, 38, 4082.
(19) Synthesis of some intermediates for 36-38, 40, and 41 has been
already reported in the literature. For R-bromination of chalcone 35,
see: Blatt, A. H. Org. Synth. Coll. Vol. 1, J ohn Wiley & Sons: New
York, 1944; p 205. (b) Lutz, R. E.; Hinkley, D. F.; J ordan, R. H. J . Am.
Chem. Soc. 1951, 73, 4647. For synthesis of (Z)-3-Bromo-4-phenylbut-
3-en-2-ol from benzylideneacetone 39 by R-bromination and reduction,
see: (c) Murphy, J . A.; Scott, K. A.; Sinclair, R. S.; Martin, C. G.;
Kennedy, A. R.; Lewis, N. J . Chem. Soc., Perkin Trans. 1 2000, 2395.
(20) We used
2 equiv of Et2Zn considering the acidity of the
sulfonamide proton of 9.

1362 J . Org. Chem., Vol. 67, No. 4, 2002
Ohno et al.
Ta ble 2. Syn th esis of Allen es Bea r in g a P r otected
Am in o Gr ou p a
Ta ble 3. Syn th esis of Allen es Bea r in g a n Alk yl or Ar yl
Gr ou p a
a
All reactions were carried out in THF at room temperature
under argon using 10 mol % of Pd(PPh3)4 and 2 equiv of Et2Zn
b
unless otherwise stated. Isolated yields. c Reactions were con-
d
ducted at 45 °C using 4 equiv of Et2Zn. Reactions were conducted
at 60 °C using 5 equiv of Et2Zn. e Relatively low yields of the allene
a
Reactions were carried out in THF at room temperature under
49 are due to its volatility.
argon using Pd(PPh3)4 (10 mol %) and Et2Zn (2 equiv), unless
otherwise stated. Isolated yields. c 4 mol % of Pd(PPh3)4 was
b
used.
and efficient synthesis of terminal allenes bearing a
protected amino group could be realized, irrespective of
the (E)- or (Z)-geometry of the substrates.
(entry 3). As we expected, when 9a was treated with Et2-
Zn in the absence of a palladium catalyst, 9a was
recovered unchanged (entry 4). Dimethylzinc was found
to be ineffective for the present transformation (entry 5).
Although Pd(OAc)2/4PPh3 gave a satisfactory result
(entry 6), Pd(OAc)2 alone or Pd(OAc)2-4PBu3 could not
be used for the present transformation reaction (entries
7 and 8). From these results, use of Pd(PPh3)4 (10 mol
%) and Et2Zn (2 equiv) proved to be the optimized
reaction conditions.
We next examined various substrates bearing an
amino group for the palladium-catalyzed reduction. As
shown in Table 2, both the (Z)- and (E)-mesylates 9a -e
and 10a -e were converted into the corresponding R-ami-
no allenes 42a -e in good to high yields by exposure to
Pd(PPh3)4 (10 mol %) and Et2Zn (2 equiv) in THF for 20
to 60 min. It was found that neither the N-protecting
group (Mts, Ts, Boc, or Mtr) nor the alkyl group on the
carbon adjacent to the nitrogen atom (i-Pr, i-Bu, or Bn)
has significant influence on the reaction. Similarly,
â-amino allene 42f and γ-amino allenes 42g and 42h
were obtained in good yields from the corresponding
mesylates. When the reaction is carried out in a relatively
large scale, decreased loading of the palladium catalyst
is recommended: starting from 4 g of 9f, the allene 42f
was obtained in 69% yield using 4 mol % of Pd(PPh3)4
(entry 11). From these results, it is clear that a simple
Syn th esis of Va r iou s Ter m in a l a n d In ter n a l Al-
len es. To expand the synthetic utility of the reaction,
we next proceeded to the synthesis of various alkyl and
aryl allenes lacking an amino group. The results are
summarized in Table 3. Monoalkyl allenes 43 and 44
were synthesized in good yields from (Z)- or (E)-mesylates
20, 21, and 23. When using the acetate 25, the reaction
proceeded quite slowly at room temperature, and pro-
longed reaction time was required. Upon heating at 45
°C, the reaction was completed within 90 min and the
desired aryl allene 45 was obtained in 60% yield (entry
4). In contrast, when using the trichloroacetate 26, the
reaction was completed at room temperature within 30
min, and 69% of the aryl allene 45 was obtained (entry
5). Similarly, bis(mesylate)s 28 and 29 were converted
into the bis(allene) 46 (entry 6, 7).21
Our allene synthesis is also applicable to the conver-
sion of secondary alcohol derivatives into the correspond-
ing internal allenes (entry 8-13). Thus, treatment of
secondary mesylate 34 with Et2Zn in the presence of
palladium(0) yielded the corresponding internal allene
(21) For recent reports describing a useful ring-forming reaction of
bis(allene)s, see: (a) Kang, S.-K.; Baik, T.-G.; Kulak, A. N.; Ha, Y.-H.;
Lim, Y.; Park, J . J . Am. Chem. Soc. 2000, 122, 11529. (b) Kang, S.-K.;
Ha, Y.-H.; Kim, D.-H.; Lim, Y.; J ung, J . Chem. Commun. 2001, 1306.

Synthesis of Allenes from Allylic Alcohol Derivatives
J . Org. Chem., Vol. 67, No. 4, 2002 1363
Sch em e 5a
F igu r e 1.
a
Reagents: (a) (COCl)2, DMSO, CH2Cl2, then (i-Pr)2NEt; (b)
chromatography. The stereochemistry of 54 was deter-
mined by degradation into a 1,2-propanediol derivative.26
After 53 was desilylated with tetrabutylammonium
fluoride, mesylation of the resulting alcohol 55 yielded
the (S,R)-mesylate 56. Similarly, 54 was converted into
the (S,S)-mesylate 58.
Ph3PdCHC(O)Me; (c) Br2; (d) DABCO; (e) DIBAL-H; (f) TBSCl,
imidazole; (g) TBAF; (h) MsCl, Et3N, DMAP.
Sch em e 6a
As shown in Scheme 6, reaction of the (S,R)-mesylate
56 with Et2Zn in the presence of catalytic Pd(PPh3)4
afforded a mixture of known amino allenes 59 and 608b
in 86% yield (59:60 ) 53:47). Similarly, the (S,S)-
mesylate 58 also gave an almost equimolar mixture of
59 and 60 (78% yield, 59:60 ) 52:48). From these results,
it is apparent that the chirality of the substrates is not
reflected to the axial chirality of the resulting allenes.
These results can be rationalized as follows (Figure
1): oxidative addition of 61 to palladium(0) will afford
π-allylpalladium(II) intermediate 62 with inversion of
configuration. While syn-1,2-elimination of palladium(II)
from 64 would give (R)-65, elimination from 67 would
give (S)-65. Since an almost 1:1 mixture of 59 and 60
was obtained from either 56 or 58 (Scheme 6), we
speculate that both 64 and 67 are competent intermedi-
ates in the reaction. The generated palladium(II) species
would be converted into palladium(0) by the action of Et2-
Zn, which is well accepted in the literature.27 Although
Et2Zn is not essential when 1 equiv of Pd(PPh3)4 was
employed (entry 3, Table 1), another mechanism via
transmetalation of the π-allylpalladium(II) intermediate
with diethylzinc cannot be ruled out.28
4722 in 77% yield (entry 8). In analogy with the synthesis
of terminal aryl allene 45 (entries 4 and 5), the acetate
36 was less reactive than the trichloroacetates 37 (com-
pare entries 9 and 10), and the reaction of the acetate
36 was completed in 2 h at 60 °C using 5 equiv of Et2Zn,
to afford 66% of diphenylallene 4823 (entry 9). The yields
of the allene 4922,24 were relatively low (53 and 55%;
entries 12 and 13), presumably due to the volatility of
49. From these observations, it is obvious that our allene
synthesis is useful for the synthesis of allenes bearing
aminoalkyl, alkyl, and aryl group(s) including terminal,
internal, and bis(allene)s. In all cases, no acetylenic
compounds were detected.
Ster eoch em ica l Cou r se of th e Rea ction of Sec-
on d a r y Mesyla tes w ith P a lla d iu m (0) a n d Dieth yl-
zin c. Finally, the influence of the stereochemistry of the
mesyloxy group, on the axial chirality of the resulting
allenes, was investigated. For ease of stereochemical
assignment, we planned to synthesize the mesylates 56
and 58 (Scheme 5), which would be precursors of known
allenes. The amino aldehyde, derived from N-protected
(S)-valinol 50,25 was allowed to react with Ph3PdCHC-
(O)Me to afford enone 51. Bromination of 51 followed by
dehydrobromination gave 52, which was reduced with
DIBAL-H to give a mixture of allylic alcohols. Since
separation of the diastereomers was quite difficult at this
stage, this mixture was directly silylated to give silyl
ethers 53 and 54, which were readily separated by flash
Con clu sion
In conclusion, we have established a reliable synthetic
method of allenes including amino allenes by palladium-
(26) Reductive debromination of 54 with Bu3SnH in the presence
of AIBN gave 74. Ozonolysis of 74 followed by reduction with NaBH4
yielded (S)-75, the optical rotation of which was in good agreement
with the authentic sample identically prepared from methyl (S)-lactate.
For synthesis of (R)-75 from methyl (R)-lactate, see: Pilli, R. A.; Victor,
M. M.; de Meijere, A. J . Org. Chem. 2000, 65, 5910.
(22) Elsevier, C. J .; Vermeer, P. J . Org. Chem. 1989, 54, 3726.
(23) (a) Elsevier, C. J .; Vermeer, P. J . Org. Chem. 1985, 50, 3042.
(b) Witt, O.; Mauser, H.; Friedl, T.; Wilhelm, D.; Clark, T. J . Org. Chem.
1998, 63, 959.
(24) (a) Caporusso, A. M.; Polizzi, C.; Lardicci, L. J . Org. Chem.
1987, 52, 3920. (b) Stemple, J . Z.; Peters, D. G. J . Org. Chem. 1989,
54, 5318.
(25) Ibuka, T.; Mimura, N.; Aoyama, H.; Akaji, M.; Ohno, H.; Miwa,
Y.; Taga, T.; Nakai, K.; Tamamura, H.; Fujii, N.; Yamamoto, Y. J . Org.
Chem. 1997, 62, 999.
(27) For a recent review, see: Knochel, P.; Almene Perea, J . J .;
J ones, P. Tetrahedron 1998, 54, 8275.

1364 J . Org. Chem., Vol. 67, No. 4, 2002
Ohno et al.
Compound 13: colorless crystals; mp 81-84 °C (n-hexane-
CHCl3 ) 1:3); 1H NMR (270 MHz) δ 2.44 (s, 3H), 2.52 (dt, J )
7.0, 6.5 Hz, 2H), 3.14 (dt, J ) 6.5, 6.5 Hz, 2H), 3.82 (s, 3H),
4.63 (br s, 1H), 7.22 (t, J ) 7.0 Hz, 1H), 7.30-7.33 (m, 2H),
7.73-7.76 (m, 2H). Anal. Calcd for C13H16BrNO4S: C, 43.11;
H, 4.45; N, 3.87. Found: C, 42.93; H, 4.45; N, 3.60.
(0)-catalyzed reduction of 2-bromo-2-propen-1-ol deriva-
tives, using diethylzinc. The reaction of the mesylates
usually gives good to high yields of the corresponding
allenes. For the synthesis of aryl allenes, however,
trichloroacetates should be used because of difficulty in
preparing the corresponding mesylates. Since both the
(Z)- and (E)-substrates were efficiently converted into the
corresponding allenes, it is unnecessary to separate these
isomers for preparative use. It was found that the center
chirality of the substrates is not reflected to the axial
chirality of the resulting allenes. Utilizing this synthetic
method, various allenes bearing aminoalkyl, alkyl, and
aryl group(s) including terminal, internal, and bis-
(allene)s can be prepared from the corresponding alde-
hydes or enones.
Compound 14: colorless oil: 1H NMR (270 MHz) δ 2.43 (s,
3H), 2.65 (dt, J ) 7.8, 6.2 Hz, 2H), 3.09 (dt, J ) 6.2, 6.2 Hz,
2H), 3.81 (s, 3H), 4.94 (m, 1H), 6.56 (t, J ) 7.8 Hz, 1H), 7.30-
7.33 (m, 2H), 7.72-7.76 (m, 2H); MS (FAB) m/z 364 (MH+,
81Br), 362 (MH+, 79Br), 242, 208, 155 (base peak), 139, 91;
HRMS (FAB) calcd C13H17BrNO4S (MH+, 79Br) 362.0062, found
362.0058.
Gen er a l P r oced u r e for th e Syn th esis of Allylic Alco-
h ols: Syn th esis of (Z)-2-Br om o-5-[N-(4-m eth ylp h en yl-
su lfon yl)a m in o]p en t-2-en -1-ol (15). To a stirred solution of
the ester 13 (2.5 g, 6.91 mmol) in a mixed solvent of CHCl3
(20 mL) and toluene (5 mL) under argon was added dropwise
DIBAL-H (1.0 M solution in toluene; 24.2 mL, 24.2 mmol) at
-78 °C, and the mixture was stirred for 2 h at this tempera-
ture. The mixture was quenched with a saturated NH4Cl
solution, and the mixture was made acidic with saturated citric
acid. The whole was extracted with EtOAc, and the extract
was washed with water, 5% NaHCO3, and water and dried
over MgSO4. Usual workup followed by flash chromatography
over silica gel with n-hexane-EtOAc (2:1) gave 15 (2.19 g, 95%
yield) as a colorless oil: 1H NMR (270 MHz) δ 2.38 (dt, J )
7.0, 6.5 Hz, 2H), 2.43 (s, 3H), 2.73 (m, 1H), 3.05 (dt, J ) 6.5,
6.5 Hz, 2H), 4.16-4.23 (m, 2H), 5.17 (m, 1H), 6.00 (t, J ) 7.0
Hz, 1H), 7.30-7.33 (m, 2H), 7.74-7.77 (m, 2H); MS (FAB) m/z
336 (MH+, 81Br), 334 (MH+, 79Br), 184 (base peak), 155, 139,
91; HRMS (FAB) calcd C12H17BrNO3S (MH+, 79Br) 334.0113,
found 334.0117.
Gen er a l P r oced u r e for th e Syn th esis of Allylic Mesy-
la tes: Syn th esis of (Z)-2-Br om o-5-[N-(4-m eth ylp h en yl-
su lfon yl)a m in o]p en t-2-en -1-yl Meth ylsu lfon a te (9f). To a
stirred mixture of the alcohol 15 (1.0 g, 2.99 mmol) and Et3N
(2.07 mL, 15.0 mmol) in THF (10 mL) was added MsCl (0.81
mL, 10.5 mmol) at -78 °C. The stirring was continued for 2 h
with warming to 0 °C, followed by quenching with 5% NaHCO3
(3 mL). The whole was extracted with Et2O-EtOAc (1:1), and
the extract was washed with 5% citric acid, water, 5%
NaHCO3, and brine and dried over MgSO4. Usual workup
followed by flash chromatography over silica gel with n-hex-
ane-EtOAc (1:1) gave 9f (1.23 g, 99% yield) as a colorless oil:
1H NMR (270 MHz) δ 2.42 (dt, J ) 7.0, 6.8 Hz, 2H), 2.44 (s,
3H), 3.08 (dt, J ) 7.0, 6.8 Hz, 2H), 3.09 (s, 3H), 4.67 (m, 1H),
4.81 (s, 2H), 6.16 (t, J ) 7.0 Hz, 1H), 7.32 (m, 2H), 7.74 (m,
2H); MS (FAB) m/z 414 (MH+, 81Br), 412 (MH+, 79Br), 316, 184
(base peak), 155, 139, 91; HRMS (FAB) calcd C13H19BrNO5S2
(MH+, 79Br) 411.9888, found 411.9871.
Gen er a l P r oced u r e for th e Syn th esis of Allylic Ac-
eta tes: Syn th esis of (Z)-3-(1,3-Ben zod ioxol-5-yl)-2-br o-
m op r op -2-en -1-yl Aceta te (25). To a stirred mixture of (2Z)-
3-(1,3-benzodioxol-5-yl)-2-bromoprop-2-en-1-ol (compound S30
in the Supporting Information; 100 mg, 0.389 mmol) and
pyridine (0.31 mL, 3.89 mmol) in THF (3 mL) was added acetic
anhydride (0.18 mL, 1.95 mmol) at -78 °C. Then, 4-(dimethyl-
amino)pyridine (4.8 mg, 0.039 mmol) was added at 0 °C, and
the mixture was stirred at this temperature for 1.5 h. The
mixture was quenched with saturated NaHCO3, and the whole
was extracted with Et2O. The extract was washed with water,
1 N HCl, water, and brine and dried over MgSO4. Usual
workup followed by column chromatography over silica gel
with n-hexane-EtOAc (5:2) gave 25 (114 mg, 98% yield) as a
colorless oil: IR (KBr) cm-1: 1740, 1221; 1H NMR (300 MHz)
δ 2.15 (s, 3H), 4.88 (s, 2H), 5.99 (s, 2H), 6.80 (d, J ) 8.1 Hz,
1H), 6.96 (s, 1H), 7.05 (dd, J ) 8.1, 1.5 Hz, 1H), 7.33 (d, J )
1.5 Hz, 1H); 13C NMR (75 MHz) δ 20.9, 70.2, 101.3, 108.1,
108.7, 117.2, 124.1, 128.4, 131.0, 147.4, 147.7, 170.3; MS (FAB)
m/z (%) 323 (MNa+, 81Br, 4), 321 (MNa+, 79Br, 3), 154 (100);
HRMS (FAB) calcd C12H11BrNaO4 (MNa+, 79Br): 320.9738.
Found 320.9735.
Exp er im en ta l Section
Gen er a l Meth od s. Melting points are uncorrected. 1H
NMR spectra were recorded in CDCl3. Chemical shifts are
reported in parts per million downfield from internal Me4Si (s
) singlet, d ) doublet, dd ) double doublet, ddd ) doublet of
double doublet, t ) triplet, q ) quartet, m ) multiplet). Optical
rotations were measured in CHCl3. For flash chromatography,
silica gel 60 H (silica gel for thin-layer chromatography, Merck)
or silica gel 60 (finer than 230 mesh, Merck) was employed.
The known compounds 9a -e,3 50,25 and 7526 were synthe-
sized according to the literature.
3-[N-(4-Meth ylp h en ylsu lfon yl)a m in o]p r op a n -1-ol (12).
To a stirred mixture of the alcohol 11 (10.2 mL, 0.13 mol) and
Et3N (36 mL, 0.26 mol) in CHCl3 (20 mL) was added a solution
of TsCl (27.3 g, 0.14 mol) in CHCl3 (30 mL) at 0 °C. The stirring
was continued for 17 h at this temperature, followed by
quenching with 5% NaHCO3 (25 mL). The whole was extracted
with EtOAc, and the extract was washed with 5% citric acid,
water, 5% NaHCO3, and brine and dried over MgSO4. Usual
workup followed by column chromatography over silica gel
with EtOAc gave 12 (30.5 g, 99% yield) as a colorless oil: 1H
NMR (270 MHz) δ 1.71 (quintet, J ) 6.2 Hz, 2H), 2.00 (t, J )
4.9 Hz, 1H), 2.43 (s, 3H), 3.10 (dt, J ) 6.2, 6.2 Hz, 2H), 3.73
(td, J ) 6.2, 4.9 Hz, 2H), 5.14 (t, J ) 6.2 Hz, 1H), 7.30-7.33
(m, 2H), 7.74-7.77 (m, 2H); MS (FAB) m/z 230 (MH+, base
peak), 212, 155, 139, 91, 74; HRMS (FAB) calcd C10H16NO3S
(MH+) 230.0851, found 230.0838.
Gen er a l P r oced u r e for th e Syn th esis of 2-Br om o-2-
en oa tes: Syn th esis of Meth yl (Z)-2-Br om o-5-[N-(4-m e-
th ylp h en ylsu lfon yl)a m in o]p en t-2-en oa te (13) a n d Its (E)-
Isom er (14). To a stirred solution of oxalyl chloride (3.13 mL,
32.7 mmol) in CH2Cl2 (15 mL) at -78 °C under argon was
added dropwise a solution of DMSO (7.73 mL, 109 mmol) in
CH2Cl2 (5 mL). After 30 min, a solution of the alcohol 12 (5.0
g, 21.8 mmol) in CH2Cl2 (20 mL) was added to the above stirred
reagent at -78 °C, and the mixture was stirred for 50 min.
Diisopropylethylamine (26.6 mL, 153 mmol) was added to the
above mixture at -78 °C, and the mixture was stirred for 30
min with warming to 0 °C. The mixture was made acidic with
saturated citric acid, and the whole was extracted with a mixed
solvent of Et2O-EtOAc (1:1). The extract was washed with
water, 5% NaHCO3, and brine, and dried over MgSO4. Con-
centration under reduced pressure gave a crude aldehyde,
which was dissolved in CHCl3 (15 mL). A solution of Ph3Pd
C(Br)CO2Me (9.9 g, 24.0 mmol) in CHCl3 (15 mL) was added
to the above stirred solution, and the mixture was stirred for
19 h at 0 °C. Concentration under reduced pressure gave a
residual oil, which was purified by flash chromatography over
silica gel with n-hexane-EtOAc (4:1) to give, in order of
elution, the (E)-enoate 14 (777 mg, 10% yield) and (Z)-enoate
13 (3.96 g, 50% yield).
(28) For recent examples of such transmetalation, see: (a) Tamaru,
Y.; Tanaka, A.; Yasui, K.; Goto, S.; Tanaka, S. Angew. Chem., Int. Ed.
1995, 34, 787. (b) Ollivier, J .; Girard, N.; Salau¨n, J . Synlett, 1999, 1539.
(c) Sakamoto, T.; Takahashi, K.; Yamazaki, T.; Kitazume, T. J . Org.
Chem. 1999, 64, 9467.
Gen er al P r ocedu r e for th e Syn th esis of Allylic Tr ich lo-
r oa ceta tes: Syn th esis of (2Z)-3-(1,3-Ben zod ioxol-5-yl)-2-

Synthesis of Allenes from Allylic Alcohol Derivatives
J . Org. Chem., Vol. 67, No. 4, 2002 1365
br om op r op -2-en -1-yl 2,2,2-Tr ich lor oa ceta te (26). To a
stirred mixture of (2Z)-3-(1,3-benzodioxol-5-yl)-2-bromoprop-
2-en-1-ol (compound S30 in the Supporting Information; 70
mg, 0.272 mmol) and Et3N (0.38 mL, 2.72 mmol) in THF (2
mL) was added trichloroacetyl chloride (0.15 mL, 1.36 mmol)
at 0 °C, and the mixture was stirred at this temperature for
30 min. The mixture was quenched with saturated NaHCO3,
and the whole was extracted with Et2O. The extract was
washed with water, saturated NH4Cl, water, and brine and
dried over MgSO4. Usual workup followed by column chroma-
tography over silica gel with n-hexane-EtOAc (10:1) gave 26
(82 mg, 75% yield) as a colorless oil. This compound is
relatively unstable: 1H NMR (300 MHz) δ 5.14 (s, 2H), 6.00
(s, 2H), 6.82 (s, J ) 7.8 Hz, 1H), 7.07 (s, 1H), 7.09 (dd, J )
7.8, 1.5 Hz, 1H), 7.38 (d, J ) 1.5 Hz, 1H).
(E)-P en ta d ec-6-en -5-on e (31). To a stirred solution of
nonyl aldehyde 30 (4.27 g, 30.0 mmol) in CHCl3 (50 mL) was
added Ph3PdCHC(O)n-Bu (16.2 g, 45.0 mmol) at 0 °C. After
the mixture was stirred for 7 h, the mixture was concentrated
under reduced pressure to leave a residual oil, which was
purified by column chromatography over silica gel with n-hex-
ane-EtOAc (30:1) to give 31 (4.13 g, 61% yield) as a colorless
oil: IR (KBr) cm-1: 1678; 1H NMR (300 MHz) δ 0.86-0.94
(m, 6H), 1.28-1.37 (m, 12H), 1.40-1.65 (m, 4H), 2.17-2.22
(m, 2H), 2.53 (t, J ) 7.5 Hz, 2H), 6.09 (d, J ) 15.6 Hz, 1H),
6.83 (dt, J ) 15.6, 6.9 Hz, 1H); 13C NMR (75 MHz) δ 13.7,
13.9, 22.3, 22.5, 26.3, 28.0, 29.1 (2C), 29.2, 31.7, 32.3, 39.7,
130.2, 147.1, 200.7; MS (FAB) m/z (%) 225 (MH+, 79Br, 100);
HRMS (FAB) calcd C15H29O (MH+, 79Br) 225.2218; found
225.2220.
followed by flash chromatography over silica gel with n-hex-
ane-EtOAc (10:1) gave 42a (38 mg, 86% yield): colorless
crystals; mp 61 °C (n-hexane); [R]30 -3.44 (c 0.524, CHCl3);
D
1H NMR (270 MHz) δ 0.84 (d, J ) 6.8 Hz, 3H), 0.88 (d, J ) 7.0
Hz, 3H), 1.75-1.87 (m, 1H), 2.30 (s, 3H), 2.63 (s, 6H), 3.56-
3.66 (m, 1H), 4.57 (d, J ) 8.6 Hz, 1H), 4.63 (dd, J ) 6.8, 2.7
Hz, 2H), 4.93 (dt, J ) 6.8, 6.8 Hz, 1H), 6.94 (s, 2H); 13C NMR
(67.8 MHz) δ 18.2, 18.3, 21.1, 23.4 (2C), 33.4, 57.6, 78.1, 90.1,
132.1 (2C), 135.0, 139.1 (2C), 142.2, 207.4. Anal. Calcd for
C
16H23NO2S: C, 65.49; H, 7.90; N, 4.77. Found: C, 65.20; H,
7.91; N, 4.67.
(4S)-6-Met h yl-4-[N-(4-m et h ylp h en ylsu lfon yl)a m in o]-
h ep t a -1,2-d ien e (42b) (Ta ble 2, en t r y 3). The mesylate
9b (45.4 mg, 0.1 mmol) was converted into 42b (24 mg, 86%
yield) by treatment with Et2Zn-Pd(0) at room temperature
for 40 min: colorless oil; [R]27D -42.5 (c 0.221, CHCl3); 1H NMR
(270 MHz) δ 0.84 (d, J ) 6.2 Hz, 3H), 0.86 (d, J ) 6.2 Hz,
3H), 1.25-1.45 (m, 2H), 1.64-1.79 (m, 1H), 2.43 (s, 3H), 3.79-
3.92 (m, 1H), 4.46 (d, J ) 8.9 Hz, 1H), 4.60 (ddd, J ) 10.8,
6.2, 2.7 Hz, 1H), 4.67 (ddd, J ) 10.8, 7.0, 2.7 Hz, 1H), 4.93
(ddd, J ) 7.0, 6.8, 6.2 Hz, 1H), 7.27-7.30 (m, 2H), 7.73-7.76
(m, 2H); 13C NMR (67.8 MHz) δ 21.7, 22.2, 22.7, 24.6, 45.6,
50.9, 78.3, 92.7, 127.5 (2C), 129.7 (2C), 138.3, 143.4, 207.0;
MS (FAB) m/z 280 (MH+), 240 (base peak), 222, 174, 155, 109,
91; HRMS (FAB) calcd C15H22NO2S (MH+) 280.1371; found:
280.1377.
(4S)-4-[N-(ter t-Bu toxyca r bon yl)a m in o]-5-p h en ylp en ta -
1,2-d ien e (42c) (Ta ble 2, en tr y 5). The mesylate 9c (65.1
mg, 0.15 mmol) was converted into 42c (32 mg, 82% yield) by
treatment with Et2Zn-Pd(0) at room temperature for 1 h:
Gen er a l P r oced u r e for th e Br om in a tion of En on es:
Syn th esis of (Z)-6-Br om op en ta d ec-6-en -5-on e (32). To a
stirred solution of the enone 31 (100 mg, 0.45 mmol) in CH2-
Cl2 (2 mL) was added dropwise bromine (40 µL, 0.81 mmol) at
-78 °C. After the mixture was stirred for 30 min at 0 °C,
1-hexene (0.07 mL, 0.54 mmol) was added to the mixture, and
the mixture was stirred for 30 min at room temperature. The
mixture was cooled to 0 °C, and Et3N (0.23 mL, 1.65 mmol) in
CH2Cl2 was added dropwise to the mixture with stirring. After
the mixture was stirred for 90 min at 0 °C, saturated NH4Cl
was added. The whole was extracted with Et2O, and the
extract was washed with saturated Na2S2O3, saturated NH4-
Cl, and brine and dried over MgSO4. Usual workup followed
by column chromatography over silica gel with n-hexane-
EtOAc (40:1) gave 32 (85 mg, 63% yield) as a colorless oil: IR
colorless needles; mp 48 °C (n-hexane); [R]26 +20.0 (c 0.274,
D
CHCl3); 1H NMR (270 MHz) δ 1.42 (s, 9H), 2.85 (dd, J ) 13.5,
7.0 Hz, 1H), 2.88-2.97 (m, 1H), 4.42 (br s, 1H), 4.57 (br s, 1H),
4.84 (dd, J ) 6.5, 3.2 Hz, 1H), 5.21 (dt, J ) 6.5, 6.5 Hz, 1H),
7.20-7.33 (m, 5H); 13C NMR (75 MHz) δ 28.3 (3C), 41.6, 49.5,
78.5, 79.4, 92.3, 126.4, 128.3 (2C), 129.6 (2C), 137.5, 155.1,
206.8. Anal. Calcd for C16H21NO2: C, 74.10; H, 8.16; N, 5.40.
Found: C, 74.02; H, 8.12; N, 5.34.
(4S)-5-P h en yl-4-[N-(2,4,6-tr im eth ylph en ylsu lfon yl)am i-
n o]p en ta -1,2-d ien e (42d ) (Ta ble 2, en tr y 7). The mesylate
9d (103 mg, 0.2 mmol) was converted into 42d (58 mg, 85%
yield) by treatment with Et2Zn-Pd(0) at room temperature
for 1 h: colorless crystals; mp 51 °C (n-hexane-Et2O ) 3:1);
1
[R]24 -15.2 (c 0.316, CHCl3); H NMR (270 MHz) δ 2.28 (s,
D
3H), 2.52 (s, 6H), 2.76-2.91 (m, 2H), 3.91-4.02 (m, 1H), 4.56-
4.68 (m, 1H), 4.70 (dd, J ) 6.8, 3.0 Hz, 2H), 5.09 (dt, J ) 6.8,
6.8 Hz, 1H), 6.87 (s, 2H), 7.03-7.08 (m, 2H), 7.17-7.24 (m,
3H); 13C NMR (67.8 MHz) δ 21.1, 23.2 (2C), 42.4, 53.1, 78.7,
92.1, 126.9, 128.7 (2C), 129.6 (2C), 132.1 (2C), 134.2, 136.7,
139.2 (2C), 142.2, 207.0. Anal. Calcd for C20H23NO2S: C, 70.35;
H, 6.79; N, 4.10. Found: C, 70.23; H, 6.80; N, 3.95.
1
(KBr) cm-1: 1691; H NMR (300 MHz) δ 0.86-0.98 (m, 6H),
1.28-1.43 (m, 12H), 1.52-1.67 (m, 4H), 2.39 (td, J ) 7.5, 7.2
Hz, 2H), 2.77 (t, J ) 7.5 Hz, 2H), 7.14 (t, J ) 7.2 Hz, 1H); 13
C
NMR (75 MHz) δ 13.8, 14.1, 22.3, 22.6, 26.7, 27.6, 29.1, 29.3
(2C), 31.8, 32.5, 38.4, 127.3, 144.8, 194.4; MS (FAB) m/z (%)
305 (MH+, 81Br, 50), 303 (MH+, 79Br, 60), 225 (100); HRMS
(FAB) calcd C15H28BrO 303.1324; found 303.1319.
(4S)-5-P h en yl-4-[N-(4-m eth oxy-2,3,6-tr im eth ylp h en yl-
su lfon yl)a m in o]p en ta -1,2-d ien e (42e) (Ta ble 2, en tr y 9).
The mesylate 9e (109 mg, 0.2 mmol) was converted into 42e
(62 mg, 83% yield) by treatment with Et2Zn-Pd(0) at room
temperature for 1 h: colorless oil; [R]24D -25.1 (c 0.693, CHCl3);
1H NMR (270 MHz) δ 2.07 (s, 3H), 2.33 (s, 3H), 2.63 (s, 3H),
2.81 (dd, J ) 13.8, 7.3 Hz, 1H), 2.86 (dd, J ) 13.8, 6.5 Hz,1H),
3.84 (s, 3H), 3.88-3.99 (m, 1H), 4.57 (d, J ) 7.0 Hz, 1H), 4.73
(dd, J ) 6.8, 3.0 Hz, 2H), 5.14 (dt, J ) 6.8, 6.8 Hz, 1H), 6.53
(s, 1H), 7.00-7.07 (m, 2H), 7.16-7.22 (m, 3H); 13C NMR (67.8
MHz) δ 12.2, 18.0, 24.7, 42.3, 53.1, 55.7, 78.7, 92.4, 112.1,
125.3, 126.9, 128.6 (2C), 129.2, 129.6 (2C), 136.8, 139.0, 139.1,
159.4, 207.1; MS (FAB) m/z 372 (MH+), 280, 230 (base peak),
213, 149, 143, 119, 91; HRMS (FAB) calcd C21H26NO3S (MH+)
372.1633; found 372.1642.
5-[N-(4-Meth ylp h en ylsu lfon yl)a m in o]p en ta -1,2-d ien e
(42f) (Ta ble 2, en tr y 11). The mesylate 9f (4.0 g, 9.71 mmol)
was converted into the allene 42f (1.58 g, 69% yield) by
treatment with Pd(PPh3)4 (448 mg, 0.388 mmol; 4 mol %) and
Et2Zn (1.0 M solution in hexane; 17.6 mL, 17.6 mmol) in THF
(40 mL) at room temperature for 30 min: colorless oil; 1H NMR
(270 MHz) δ 2.15 (dtt, J ) 6.8, 6.8, 3.0 Hz, 2H), 2.43 (s, 3H),
3.05 (dt, J ) 6.8, 6.8 Hz, 2H), 4.58-4.65 (m, 1H), 4.69 (dt, J )
6.8, 3.0 Hz, 2H), 4.99 (tt, J ) 6.8, 6.8 Hz, 1H), 7.31 (m, 2H),
(Z)-6-Br om op en ta d ec-6-en -5-ol (33). By a procedure iden-
tical with that described for the synthesis of 15, the enone 32
(850 mg, 2.8 mmol) was converted into the alcohol 33 (476 mg,
1
56% yield): colorless oil; IR (KBr) cm-1: 3354; H NMR (300
MHz) δ 0.86-0.94 (m, 6H), 1.20-1.43 (m, 16H), 1.61-1.70 (m,
2H), 1.92 (d, J ) 6.3 Hz, 1H), 2.20 (td, J ) 7.2, 6.9 Hz, 2H),
4.04 (td, J ) 6.3, 6.3 Hz, 1H), 5.95 (t, J ) 6.9 Hz, 1H); 13C
NMR (75 MHz) δ 14.0, 14.1, 22.4, 22.6, 27.5, 28.3, 29.2 (2C),
29.4, 30.7, 31.8, 35.3, 76.7, 130.5, 131.4; MS (FAB) m/z (%)
305 (MH+, 81Br, 6), 303 (MH+, 79Br, 6), 137 (100); HRMS (FAB)
calcd C15H29BrNaO (MNa+, 79Br) 327.1299; found 327.1304.
Gen er a l P r oced u r e for th e Syn th esis of Allen es fr om
Activa ted Allylic Alcoh ols by a Et 2Zn /P d (0) System .
Syn th esis of (4S)-5-Meth yl-4-[N-(2,4,6-tr im eth ylp h en yl-
su lfon yl)a m in o]h exa -1,2-d ien e (42a ) fr om th e Mesyla te
(9a ) (Ta ble 2, en tr y 1). To a stirred solution of the mesylate
9a (70.3 mg, 0.15 mmol) and Pd(PPh3)4 (17.3 mg, 10 mol %,
0.015 mmol) in dry THF (1 mL) under argon was added Et2-
Zn (1.1 M in toluene; 0.273 mL, 0.3 mmol) at room tempera-
ture. The mixture was stirred for 1 h at this temperature
followed by quenching with saturated aqueous NH4Cl (1 mL).
The whole was extracted with Et2O, and the extract was
washed with water and dried over MgSO4. Usual workup

1366 J . Org. Chem., Vol. 67, No. 4, 2002
Ohno et al.
7.75 (m, 2H); 13C NMR (67.8 MHz) δ 21.7, 28.4, 42.4, 70.1,
86.6, 127.2 (2C), 129.9 (2C), 137.1, 143.6, 208.9; MS (FAB) m/z
238 (MH+, base peak), 237, 184, 155, 139, 86, 83, 82; HRMS
(FAB) calcd C12H16NO2S (MH+) 238.0902; found 238.0908.
(6S)-7-Meth yl-6-[N-(2,4,6-tr im eth ylph en ylsu lfon yl)am i-
n o]octa -1,2-d ien e (42g) (Ta ble 2, en tr y 13). The mesylate
9g (25 mg, 0.05 mmol) was converted into 42g (11 mg, 68%
yield) and 2-(1-bromovinyl)-5-isopropyl-N-(2,4,6-trimethylphe-
nylsulfonyl)pyrrolidine (3 mg, 15% yield) by treatment with
Et2Zn-Pd(0) at room temperature for 45 min: colorless
28.5 (2C), 29.27 (2C), 29.32 (2C), 29.6 (2C), 74.7 (2C), 90.3 (2C),
208.7 (2C); MS (CI) m/z 191 (MH+), 189, 135, 121, 109, 95 (base
peak), 81; HRMS (CI) calcd C14H23 (MH+) 191.1799; found:
191.1805.
P en ta d eca -5,6-d ien e (47) (Ta ble 3, en tr y 8). To a stirred
mixture of the alcohol 33 (50.0 mg, 0.164 mmol) and Et3N (0.11
mL, 0.820 mmol) in THF (3 mL) were added MsCl (0.025 mL,
0.328 mmol) and 4-(dimethylamino)pyridine (20 mg, 0.164
mmol) at -78 °C. The stirring was continued for 12 h at 40
°C, followed by quenching with saturated NaHCO3. The whole
was extracted with Et2O, and the extract was washed with
water, 1 N HCl, water, and brine and dried over MgSO4.
Concentration under reduced pressure gave a crude mesylate
34 (51.5 mg, 82% yield), which was used without further
purification due to its instability toward silica gel. According
to the general procedure, the crude mesylate 34 (50 mg, 0.130
mmol) was converted into 47 (26.1 mg, 77% yield) by treatment
with Et2Zn-Pd(0) at room temperature for 15 min: colorless
oil; 1H NMR (300 MHz) δ 0.88 (t, J ) 7.2 Hz, 3H), 0.90 (t, J )
7.2 Hz, 3H), 1.25-1.46 (m, 16H), 1.93-2.02 (m, 4H), 5.03-
5.09 (m, 2H); 13C NMR (75 MHz) δ 13.9, 14.1, 22.2, 22.7, 28.7,
29.0, 29.1, 29.2, 29.3, 29.4, 31.4, 31.9, 90.8, 90.9, 203.8; all the
data for 47 were in good agreement with the literature.22
1,3-Dip h en ylp r op a -1,2-d ien e (48) (Ta ble 3, en tr y 10).
The trichloroacetate 37 (26 mg, 0.058 mmol) was converted
into 48 (9.1 mg, 83% yield) by treatment with Et2Zn-Pd(0) at
room temperature for 30 min: colorless oil; 1H NMR (300 MHz)
δ 6.50 (s, 2H), 7.10-7.28 (m, 10H); 13C NMR (75 MHz) δ 98.4
(2C), 127.0 (4C), 127.3 (2C), 128.7 (4C), 133.6 (2C), 207.8: this
compound appeared to be unstable when exposed to air and
light; all the data for 48 were in good agreement with the
literature.23
crystals; mp 53 °C (n-hexane); [R]24 -2.66 (c 0.601, CHCl3);
D
1H NMR (270 MHz) δ 0.72 (d, J ) 6.8 Hz, 3H), 0.79 (d, J ) 6.8
Hz, 3H), 1.30-1.57 (m, 2H), 1.61-2.02 (m, 3H), 2.30 (s, 3H),
2.64 (s, 6H), 3.14 (ddt, J ) 8.9, 8.9, 4.3 Hz, 1H), 4.35 (d, J )
8.9 Hz, 1H), 4.64 (dt, J ) 6.5, 3.2 Hz, 2H), 4.94 (tt, J ) 6.5,
6.5 Hz, 1H), 6.94 (s, 2H); 13C NMR (67.8 MHz) δ 17.8, 18.4,
21.1, 23.4 (2C), 24.4, 31.2, 31.5, 58.6, 75.6, 89.4, 132.1 (2C),
135.5, 138.7 (2C), 142.0, 208.5; MS (CI) m/z 322 (MH+, base
peak), 254, 139, 123; HRMS (CI) calcd C18H28NO2S (MH+)
322.1840; found 322.1831. (5S)-2-(1-Br om ovin yl)-5-isop r o-
p yl-N-(2,4,6-tr im eth ylp h en ylsu lfon yl)p yr r olid in e: color-
1
less oil; H NMR (270 MHz) δ 0.69 (d, J ) 6.8 Hz, 3H), 0.82
(d, J ) 6.8 Hz, 3H), 1.95 (m, 4H), 2.30 (s, 3H), 2.67 (s, 6H),
3.65 (td, J ) 6.5, 3.8 Hz, 1H), 4.43 (t, J ) 7.6 Hz, 1H), 5.35 (d,
J ) 1.4 Hz, 1H), 5.76 (d, J ) 1.4 Hz, 1H), 6.93 (s, 2H); MS
(CI) m/z 402 (MH+, 81Br; base peak), 400 (MH+, 79Br), 356, 322,
321, 218, 183; HRMS (CI) calcd C18H27BrNO2S (MH+, 79Br)
400.0946; found 400.0950.
5-[(4R)-N-(ter t-Bu t oxyca r b on yl)-2,2-d im et h yl-1,3-ox-
a zolid in -4-yl]p en ta -1,2-d ien e (42h ) (Ta ble 2, en tr y 14).
The mesylate 9h (40 mg, 0.090 mmol) was converted into 42h
(16.8 mg, 69% yield) by treatment with Et2Zn-Pd(0) at room
temperature for 1 h: colorless oil; [R]21D -19.7 (c 0.811, CHCl3);
1H NMR (270 MHz) δ 1.48 (m, 9H), 1.50-2.05 (m, 10H), 3.73-
3.96 (m, 3H), 4.68 (m, 2H), 5.07-5.15 (m, 1H); 13C NMR (75
MHz, 323 K) δ 25.4 (2C), 27.4, 28.8 (3C), 33.2, 57.4, 67.3, 75.2,
80.0, 89.5, 93.8, 152.3, 209.0; MS (FAB) m/z 268 (MH+), 252,
4-P h en ylbu ta -2,3-d ien e (49) (Ta ble 3, en tr y 12). The
trichloroacetate 40 (100 mg, 0.268 mmol) was converted into
48 (18 mg, 53% yield) by treatment with Et2Zn-Pd(0) at room
1
temperature for 15 min: colorless oil; H NMR (300 MHz) δ
1.78 (dd, J ) 6.9, 3.0 Hz, 3H), 5.53 (qd, J ) 6.9, 6.6 Hz, 1H),
6.09 (dq, J ) 6.6, 3.0 Hz, 1H), 7.14-7.32 (m, 5H); 13C NMR
(75 MHz) δ 14.1, 89.6, 93.9, 126.6 (3C), 128.5 (2C), 135.0, 206.1;
all the data for 49 were in good agreement with the litera-
ture.22,24
212, 168, 154, 57 (base peak), 55; HRMS (FAB) calcd C15H26
-
NO3 (MH+) 268.1913; found 268.1936.
5-P h en ylp en ta -1,2-d ien e (43) (Ta ble 3, en tr y 1). The
mesylate 20 (160 mg, 0.50 mmol) was converted into 43 (56
mg, 78% yield) by treatment with Et2Zn-Pd(0) at room
temperature for 1 h: colorless oil; 1H NMR (270 MHz) δ 2.26-
2.37 (m, 2H), 2.73 (t, J ) 8.1 Hz, 2H), 4.67 (dt, J ) 6.8, 3.5
Hz, 2H), 5.15 (tt, J ) 13.5, 6.8 Hz, 1H), 7.16-7.31 (m, 5H);
13C NMR (67.8 MHz) δ 30.2, 35.6, 75.4, 89.6, 126.1, 128.5 (2C),
128.7 (2C), 142.0, 208.8; MS (CI) m/z 145 (MH+, base
peak), 91, 61; HRMS (CI) calcd C11H13(MH+) 145.1017; found
145.1019.
(5S,3E)-6-Meth yl-5-[N-(2,4,6-tr im eth ylp h en ylsu lfon yl)-
a m in o]h ep t-3-en -2-on e (51). To a stirred solution of oxalyl
chloride (3.74 mL, 39.0 mmol) in CH2Cl2 (45 mL) at -78 °C
under argon was added dropwise a solution of DMSO (10.6
mL, 150 mmol) in CH2Cl2 (15 mL). After 30 min, a solution of
the alcohol 50 (8.55 g, 30.0 mmol) in CH2Cl2 (15 mL) was added
to the above stirred reagent at -78 °C, and the mixture was
stirred for 1 h. Diisopropylethylamine (36.6 mL, 210 mmol)
was added to the above mixture at -78 °C, and the mixture
was stirred for 30 min with warming to 0 °C. The mixture was
made acidic with 1 N HCl, and the whole was extracted with
Et2O. The extract was washed with water and brine, and dried
over MgSO4. Concentration under reduced pressure gave a
crude aldehyde. To a stirred solution of the aldehyde in CHCl3
(50 mL) was added Ph3PdCHC(O)Me (12.4 g, 39.0 mmol), and
the mixture was stirred at 0 °C overnight. Concentration under
reduced pressure gave a residual oil, which was purified by
column chromatography over silica gel with n-hexane-EtOAc
(11:4) to give 51 (7.43 g, 77% yield): colorless crystals; mp 91
5-(3,4-Dim eth oxyp h en yl)p en ta -1,2-d ien e (44) (Ta ble 3,
en tr y 3). The mesylate 23 (200 mg, 0.53 mmol) was converted
into 44 (74 mg, 69% yield) by treatment with Et2Zn-Pd(0) at
room temperature for 2 h: colorless oil; 1H NMR (270 MHz) δ
2.24-2.35 (m, 2H), 2.68 (t, J ) 8.4 Hz, 2H), 3.86 (s, 3H), 3.87
(s, 3H), 4.68 (dt, J ) 6.5, 3.2 Hz, 2H), 5.15 (tt, J ) 6.5, 6.5 Hz,
1H), 6.72-6.81 (m, 3H); 13C NMR (67.8 MHz) δ 30.4, 35.2, 56.0,
56.1, 75.3, 89.6, 111.3, 112.0, 120.4, 134.6, 147.4, 148.9, 208.7;
MS (CI) m/z 205 (MH+, base peak), 204, 151; HRMS (CI) calcd
C
13H17O2 (MH+) 205.1228; found 205.1233.
(2Z)-3-(1,3-Ben zodioxol-5-yl)pr opa-1,2-dien e (45) (Table
3, en tr y 5). The trichloroacetate 26 (80 mg, 0.199 mmol) was
converted into 45 (22 mg, 69%) by treatment with Et2Zn-Pd-
(0) at room temperature for 30 min: colorless oil; IR (KBr)
°C (n-hexane-EtOAc); [R]28 -36.4 (c 1.03, CHCl3); IR (KBr)
D
cm-1: 3284, 1678, 1325; 1H NMR (270 MHz) δ 0.84 (d, J ) 7.0
Hz, 3H), 0.92 (d, J ) 7.0 Hz, 3H), 1.72-1.88 (m, 1H), 2.02 (s,
3H), 2.27 (s, 3H), 2.62 (s, 6H), 3.62-3.70 (m, 1H), 4.93 (d, J )
7.8 Hz, 1H), 5.83 (dd, J ) 16.2, 1.1 Hz, 1H), 6.31 (dd, J ) 16.2,
7.2 Hz, 1H), 6.92 (s, 2H); 13C NMR (67.5 MHz) δ 18.4, 18.5,
20.9, 23.1 (2C), 27.2, 32.7, 60.5, 131.4, 131.8 (2C), 134.4, 138.7
(2C), 142.2, 143.4, 197.1. Anal. Calcd for C17H25NO3S: C, 63.13;
H, 7.79; N, 4.33. Found: C, 62.97; H, 7.66; N, 4.28.
1
cm-1: 1942, 1240; H NMR (300 MHz) δ 5.12 (d, J ) 6.9 Hz,
2H), 5.93 (s, 2H), 6.09 (t, J ) 6.9 Hz, 1H), 6.70-6.76 (m, 2H),
6.83 (s, 1H); 13C NMR (75 MHz) δ 79.0, 93.8, 101.0, 106.6,
108.3, 120.3, 127.9, 146.6, 148.0, 209.3; MS (EI) m/z (%) 160
(M+, 100); HRMS (EI) calcd C10H8O2 (M+) 160.0524; found
160.0586.
Tet r a d eca -1,2,12,13-t et r a en e (46) (Ta b le 3, en t r y 6).
The mesylate 28 (200 mg, 0.37 mmol) was converted into 46
(54 mg, 77% yield) by treatment with Et2Zn-Pd(0) at room
temperature for 1.5 h: colorless oil; 1H NMR (270 MHz) δ
1.28-1.47 (m, 12H), 1.94-2.04 (m, 4H), 4.65 (dt, J ) 6.8, 3.0
Hz, 4H), 5.09 (tt, J ) 6.8, 6.8 Hz, 2H); 13C NMR (67.8 MHz) δ
(5S,3Z)-3-Br om o-6-m eth yl-5-[N-(2,4,6-tr im eth ylp h en yl-
su lfon yl)a m in o]h ep t-3-en -2-on e (52). By a procedure iden-
tical with that described for the synthesis of 32 except that
DABCO (3.36 g, 221 mmol) was used instead of Et3N for
dehydrobromination, 51 (5.50 g, 17.0 mmol) was converted into
the alcohol 52 (3.28 g, 75% yield): colorless crystals; mp 158

Synthesis of Allenes from Allylic Alcohol Derivatives
J . Org. Chem., Vol. 67, No. 4, 2002 1367
°C (n-hexane-CHCl3); [R]24 +37.2 (c 1.03, CHCl3); IR (KBr)
of 9f, the alcohol 55 (40 mg, 0.099 mmol) was converted into
the mesylate 56 (42 mg, 87% yield): colorless oil; [R]24D +68.4
(c 0.83, CHCl3); IR (KBr) cm-1: 3334, 1356, 1157; 1H NMR
(300 MHz) δ 0.93 (d, J ) 6.9 Hz, 3H), 0.95 (d, J ) 7.2 Hz, 3H),
1.28 (d, J ) 6.3 Hz, 3H), 1.82-1.93 (m, 1H), 2.29 (s, 3H), 2.63
(s, 6H), 2.97 (s, 3H), 3.96 (ddd, J ) 9.0, 8.7, 5.7 Hz, 1H), 4.93-
4.99 (m, 2H), 5.88 (d, J ) 9.0 Hz, 1H), 6.93 (s, 2H); 13C NMR
(75 MHz) δ 17.9, 18.4, 20.2, 20.8, 23.0 (2C), 32.8, 39.1, 58.9,
80.6, 126.5, 132.0 (2C), 133.3, 134.1, 139.1 (2C), 142.2; MS
(FAB) m/z (%) 484 (MH+, 81Br, 1), 482 (MH+, 79Br, 1), 136 (100);
HRMS (FAB) calcd C18H29BrNO5S2 (MH+, 79Br) 482.0671;
found 482.0658.
(5S,a S)-6-Meth yl-5-[N-(2,4,6-tr im eth ylp h en ylsu lfon yl)-
a m in o]h ep t -2,3-d ien e (59) a n d It s (5S,a R)-Isom er (60).
According to the general procedure for the synthesis of allenes,
the mesylate 56 (40 mg, 0.083 mmol) was converted into a
mixture of the allenes 59 and 60 (22 mg, 86% yield; 59:60 )
53:47) by treatment with Pd(PPh3)4 (12.0 mg, 0.010 mmol) and
Et2Zn (1.02 M in hexane; 0.20 mL, 0.204 mmol) at room
temperature for 30 min. 1H NMR spectra of this diastereomeric
mixture was in good agreement with those of the authentic
samples.8b
D
cm-1: 3296, 1693, 1323; 1H NMR (270 MHz) δ 0.92 (d, J ) 7.0
Hz, 3H), 0.97 (d, J ) 7.0 Hz, 3H), 1.88-2.01 (m, 1H), 2.21 (s,
3H), 2.27 (s, 3H), 2.64 (s, 6H), 4.08 (ddd, J ) 8.9, 7.6, 5.7 Hz,
1H), 5.16 (d, J ) 7.6 Hz, 1H), 6.67 (d, J ) 8.9 Hz, 1H), 6.92 (s,
2H); 13C NMR (67.5 MHz) δ 18.1, 18.8, 20.9, 23.1 (2C), 26.1,
32.6, 60.2, 127.1, 131.9 (2C), 133.7, 139.2 (2C), 142.4, 143.1,
190.9. Anal. Calcd for C17H24BrNO3S: C, 50.75; H, 6.01; N,
3.48. Found: C, 50.82; H, 5.96; N, 3.47.
(2R,5S,3Z)-3-Br om o-O-ter t-bu tyld im eth ylsilyl-6-m eth -
yl-5-[N-(2,4,6-tr im eth ylp h en ylsu lfon yl)a m in o]h ep t-3-en -
2-ol (53) a n d It s (2S,5S,3Z)-Isom er (54). By a procedure
identical with that described for the synthesis of 15, the enone
52 (300 mg, 0.75 mmol) was converted into an inseparable
mixture of diastereomeric alcohols (247 mg, 82% yield). To a
stirred solution of this diastereomixture of the alcohols (1.70
g, 4.2 mmol) in a mixed solvent of CHCl3 (20 mL) and DMF
(20 mL) were successively added imidazole (1.15 g, 16.8 mmol)
and tert-butyldimethylsilyl chloride (1.89 g, 12.6 mmol) at 0
°C, and the mixture was stirred for 3 h at room temperature.
Water was added to the mixture, and the whole was extracted
with Et2O. The extract was washed with 1 N HCl, water, and
brine and dried over MgSO4. Usual workup followed by flash
chromatography over silica gel with n-hexane-EtOAc (20:1)
gave, in order of elution, 54 (0.73 g, 34%) and 53 (0.94 g, 44%).
(2S,5S,3E)-O-ter t-Bu t yld im et h ylsilyl-6-m et h yl-5-[N-
(2,4,6-tr im eth ylph en ylsu lfon yl)am in o]h ept-3-en -2-ol (74).
To a stirred solution of 54 (200 mg, 0.386 mmol) in benzene (5
mL) were successively added n-Bu3SnH (0.62 mL, 2.32 mmol)
and AIBN (19 mg, 0.116 mmol) at room temperature, and the
mixture was heated under reflux for 16 h. Aqueous 10% KF
was added to the mixture, and the resulting precipitate was
filtered and washed with Et2O. The filtrate was concentrated
under reduced pressure to leave an oily residue, which was
purified by column chromatography over silica gel with n-hex-
ane-EtOAc (5:2) to give 74 (86.2 mg, 52%): colorless solid;
mp 44-47 °C; IR (KBr) cm-1: 3292, 1323; 1H NMR (270 MHz)
δ -0.02 (s, 3H), 0.00 (s, 3H), 0.82-0.89 (m, 15H), 0.94 (d, J )
6.2 Hz, 3H), 1.71-1.81 (m, 1H), 2.28 (s, 3H), 2.63 (s, 6H), 3.52-
3.59 (m, 1H), 4.05-4.14 (m, 1H), 4.49 (d, J ) 7.6 Hz, 1H),
5.28-5.31 (m, 2H), 6.91 (s, 2H); 13C NMR (67.5 MHz) δ -4.8,
-4.7, 18.0, 18.2, 18.5, 20.9, 23.2 (2C), 23.9, 25.8 (3C), 33.1,
60.6, 67.6, 124.7, 131.8 (3C), 137.3, 138.5 (2C), 141.6; MS (FAB)
Compound 53: colorless crystals; mp 102 °C (n-hexane);
1
[R]24 +46.3 (c 1.03, CHCl3); IR (KBr) cm-1: 3273, 1323; H
D
NMR (300 MHz) δ -0.02 (s, 3H), 0.00 (s, 3H), 0.85 (s, 9H),
0.88 (d, J ) 6.9 Hz, 3H), 0.89 (d, J ) 6.9 Hz, 3H), 1.08 (d, J )
6.3 Hz, 3H), 1.80-1.91 (m, 1H), 2.26 (s, 3H), 2.62 (s, 6H), 3.97
(ddd, J ) 9.0, 7.5, 5.1 Hz, 1H), 4.06 (q, J ) 6.3 Hz, 1H), 4.60
(d, J ) 7.5 Hz, 1H), 5.69 (d, J ) 9.0 Hz, 1H), 6.90 (s, 2H); 13
C
NMR (75 MHz) δ -5.0, -4.9, 18.0, 18.1, 18.2, 20.9, 23.1 (2C),
23.3, 25.7 (3C), 53.1, 58.9, 72.7, 125.7, 131.9 (2C), 134.3, 134.7,
139.0 (2C), 142.0. Anal. Calcd for C23H40BrNO3SSi: C, 53.27;
H, 7.77; N, 2.70. Found: C, 53.52; H, 7.68; N, 2.70.
Compound 54: colorless crystals; mp 59 °C (n-hexane); [R]25
D
+36.4 (c 1.03, CHCl3); IR (KBr) cm-1: 3302, 1323; H NMR
1
(300 MHz) δ -0.03 (s, 3H), 0.00 (s, 3H), 0.85 (s, 9H), 0.91 (d,
J ) 6.6 Hz, 6H), 1.00 (d, J ) 6.3 Hz, 3H), 1.81-1.92 (m, 1H),
2.26 (s, 3H), 2.63 (s, 6H), 4.02 (ddd, J ) 9.0, 8.1, 5.4 Hz, 1H),
4.09 (qd, J ) 6.3, 1.2 Hz, 1H), 4.65 (d, J ) 8.1 Hz, 1H), 5.76
(dd, J ) 9.0, 1.2 Hz, 1H), 6.90 (s, 2H); 13C NMR (75 MHz) δ
-5.2, -5.1, 18.0 (2C), 18.1, 20.8, 22.7, 23.1 (2C), 25.6 (3C), 33.2,
59.1, 72.2, 124.2, 132.0 (2C), 133.2, 134.6, 138.9 (2C), 141.8;
MS (FAB) m/z (%) 542 (MNa+, 81Br, 100), 540 (MNa+, 79Br,
88); HRMS (FAB) calcd C23H40BrNNaO3SSi (MNa+, 79Br)
540.1579; found 540.1602.
m/z (%) 462 (MNa+, 60), 73 (100); HRMS (FAB) calcd C23H41
-
NNaO3SSi (MNa+) 462.2474; found 462.2459.
(2S)-2-(ter t-Bu t yld im et h ylsilyloxy)p r op a n -1-ol (75).
Ozone was bubbled through a solution of 74 (40.0 mg, 0.091
mmol) in CH2Cl2 (3 mL) until blue color persisted (ca. 30 min).
A solution of NaBH4 (25.8 mg, 0.683 mmol) in a mixed solvent
of EtOH-H2O (1:1) was added to the mixture, and the mixture
was stirred for 1.5 h. Concentration under reduced pressure
gave an oily residue. Aqueous 1 N HCl was added, and the
whole was immediately extracted with Et2O. The extract was
washed with brine and dried over MgSO4. Usual workup
followed by column chromatography over silica gel with
n-hexane-EtOAc (7:2) gave 75 (1.6 mg, 9%). All the spectro-
scopic data were in good agreement with the authentic sample
of 75, which was identically prepared from methyl (S)-lactate.26
(2R,5S,3Z)-3-Br om o-6-m eth yl-5-[N-(2,4,6-tr im eth ylp h e-
n ylsu lfon yl)a m in o]h ep t-3-en -2-ol (55). To a stirred solution
of 53 (200 mg, 0.386 mmol) in THF (2 mL) was added
tetrabutylammonium fluoride (1.0 M in THF; 2.7 mL, 2.7
mmol), and the mixture was stirred for 4 h with warming to
room temperature. The mixture was made acidic with 1 N HCl,
and the whole was extracted with Et2O. The extract was
washed with water, saturated NaHCO3, and brine and dried
over MgSO4. Usual workup followed by column chromatogra-
phy over silica gel with n-hexane-EtOAc (5:3) gave 55 (146
mg, 94% yield): colorless crystals; mp 105 °C (n-hexane-
Ack n ow led gm en t. This article is dedicated to the
memory of Prof. Toshiro Ibuka, deceased on J anuary
20, 2000. This work was supported by a Grant-in-Aid
for Encouragement of Young Scientists from the Min-
istry of Education, Science, Sports and Culture of J apan.
S.O. is grateful to Research Fellowships of the J apan
Society for the Promotion of Science for Young Scien-
tists.
EtOAc); [R]27 +92.7 (c 0.28, CHCl3); IR (KBr) cm-1: 3471,
D
1
3313, 1319; H NMR (300 MHz) δ 0.88 (d, J ) 6.9 Hz, 3H),
0.92 (d, J ) 6.9 Hz, 3H), 1.17 (d, J ) 6.0 Hz, 3H), 1.76-1.87
(m, 1H), 1.88 (d, J ) 4.5 Hz, 1H), 2.30 (s, 3H), 2.65 (s, 6H),
3.96-4.13 (m, 2H), 4.94 (d, J ) 7.8 Hz, 1H), 5.65 (d, J ) 8.7
Hz, 1H), 6.95 (s, 2H); 13C NMR (75 MHz) δ 18.1, 18.3, 20.8,
21.7, 23.1 (2C), 32.9, 59.4, 72.3, 125.9, 131.8 (2C), 133.9, 134.8,
139.4 (2C), 142.2; MS (FAB) m/z (%) 406 (MH+, 81Br, 4), 404
(MH+, 79Br, 6), 119 (100); HRMS (FAB) calcd C17H27BrNO3S
(MH+, 79Br) 404.0895; found 404.0899.
Su p p or tin g In for m a tion Ava ila ble: Synthetic proce-
dures and characterization for 9c, 9g, 9h , 10a -f, 16, 20, 21,
23, 28, 29, 36-38, 40, 41, 57, and 58; 1H NMR spectra for all
new compounds. This material is available free of charge via
the Internet at http://pubs.acs.org.
(2R,5S,3Z)-3-Br om o-6-m eth yl-5-[N-(2,4,6-tr im eth ylp h e-
n ylsu lfon yl)a m in o]h ep t-3-en -2-yl Meth ylsu lfon a te (56).
By a procedure identical with that described for the synthesis
J O016320Y