Base-catalyzed endo-mode cyclization of allenes: Easy preparation of five- to nine-membered oxacycles

Article abstract of DOI:10.1021/jo0488614

A reliable and efficient procedure for constructing five- to eight-membered oxacycles has been developed. Allenes with both a phosphoryl group and a suitable δ-hydroxyalkyl side chain at the C₁-position underwent an endo mode ring-closing react

Full text of DOI:10.1021/jo0488614

Ba se-Ca ta lyzed En d o-Mod e Cycliza tion of Allen es: Ea sy
P r ep a r a tion of F ive- to Nin e-Mem ber ed Oxa cycles
Chisato Mukai,* Masaru Ohta, Haruhisa Yamashita, and Shinji Kitagaki
Division of Pharmaceutical Sciences, Graduate School of Natural Science and Technology, Kanazawa
University, Kakuma-machi, Kanazawa 920-1192, J apan
cmukai@kenroku.kanazawa-u.ac.jp
Received J uly 6, 2004
A reliable and efficient procedure for constructing five- to eight-membered oxacycles has been
developed. Allenes with both a phosphoryl group and a suitable δ-hydroxyalkyl side chain at the
C1-position underwent an endo mode ring-closing reaction to give five- to seven-membered oxacycles.
Changing the phosphoryl group to a phosphono functionality facilitated the preparation of eight-
membered congeners. Introduction of a cis double bond to the alkyl side chain of the starting allenes
made possible the easy formation of medium-sized oxacycles, such as the dihydrooxocin and
tetrahydrooxonin frameworks, regardless of the electron-withdrawing group (POPh2, PO(OEt)2,
SOPh, and SO2Ph) at the C1-position.
SCHEME 1
In tr od u ction
Various kinds of oxacycles have been shown to be the
major component of many biologically important natural
products.1 In a previous paper,2 we reported a novel and
efficient method for the preparation of five- to seven-
membered oxacycles 4 (n ) 1-3) from propargyl alcohol
derivatives 1 (n ) 1-3) (Scheme 1). This procedure
involves the known [2,3]-sigmatropic rearrangement of
the propargyl alcohol with benzenesulfenyl chloride (Ph-
SCl),3 followed by the novel base-catalyzed endo-mode
ring closure of the resulting allenyl sulfoxides 2 (n )
1-3).4 However, the ring-closing reaction of 2 (n ) 4)
under the standard basic conditions, leading to the
construction of eight-membered oxacycles 4 (n ) 4), was
unsuccessful. To overcome this drawback, the sulfonyl
functionality, which was anticipated to increase the
reactivity of the allenyl moiety as a formal Michael
acceptor, was used as an electron-withdrawing group for
this endo-mode ring-closing reaction. Thus, the allenyl
sulfone derivatives 3 (n ) 1-4), prepared by oxidation
of the allenyl sulfoxides 2 (n ) 1-4), were subjected to
basic conditions resulting in the formation of the five- to
eight-membered oxacycles 5 (n ) 1-4) in high yields.5
A similar protocol using phosphorus reagents6 instead
of PhSCl would provide oxacycles with a phosphoryl or
a phosphono functionality, which should be very useful
for further manipulations if the endo-mode ring-closing
reaction proceeded as anticipated.7,8 In addition, several
natural products possess a monocyclic eight- or nine-
membered oxacycle as a core framework with an internal
double bond.1 Therefore, it would be interesting to
investigate the synthesis of medium-sized oxacycles with
an internal double bond by applying the newly developed
endo-mode ring-closing reaction of allenes. Thus, our
endeavors were directed toward (i) the examination of
the ring-closing reaction of allenylphosphine oxides as
well as allenylphosphonate derivatives and (ii) the prepa-
ration of eight- and nine-membered oxacycles with an
internal double bond (dihydrooxocin and tetrahydrooxo-
nin, respectively).
* To whom correspondence should be addressed. Tel: +81-76-234-
4411. Fax: +81-76-234-4410.
(1) (a) Moore, R. E. In Marine Natural Products: Chemical and
Biological Perspectives; Scheuer, P. J ., Ed.; Academic Press: New York,
1978; Vol. 1, pp 43-124. (b) Faulkner, D. J . Nat. Prod. Rep. 1986, 3,
1-33. (c) Yasumoto, T.; Murata, M. Chem. Rev. 1993, 93, 1897-1909.
(d) Faulkner, D. J . Nat. Prod. Rep. 1996, 13, 75-125.
(2) Mukai, C.; Yamashita, H.; Hanaoka, M. Org. Lett. 2001, 3, 3385-
3387.
(5) Dai described an exo-mode cyclization of the allenyl sulfone
derivatives resulting in a formation of the five-membered oxacycles:
Dai, W.-M.; Lee, M. Y. H. Tetrahedron 1998, 54, 12497-12512.
(6) (a) Nicolaou, K. C.; Maligres, P.; Shin, J ,; de Leon, E.; Rideout,
D. J . Am. Chem. Soc. 1990, 112, 7825-7826. (b) Curtin, M. L.;
Okamura, W. H. J . Org. Chem. 1990, 55, 5278-5287.
(7) A similar endo-mode ring-closing reaction of trisubstituted
allenylphosphine oxides, leading to the dihydrofuran skeleton, has been
reported: Pravia, K.; White, R.; Fodda, R.; Maynard, D. F. J . Org.
Chem. 1996, 61, 6031-6032.
(3) Horner, L.; Binder, V. Liebigs Ann. Chem. 1972, 757, 33-68.
(4) Parsons reported an exo-mode ring-closing reaction of allenyl
sulfoxide derivatives; see: (a) Pairaudeau, G.; Parsons, P. J .; Under-
wood, J . M. J . Chem. Soc., Chem. Commun. 1987, 1718-1720. (b) Gray,
M.; Parsons, P. J .; Neary, A. P. Synlett 1992, 597-598. (c) Gray, M.;
Parsons, P. J .; Neary, A. P. Synlett 1993, 281-282. (d) Parsons, P. J .;
Stefinovic, M. Synlett 1993, 931-932. (e) Edwards, N.; Macritchie, J .
A.; Parsons, P. J .; Drew, M. G. B.; J ahans, A. W. Tetrahedron 1997,
53, 12651-12660.
(8) Brel reported an exo-mode cyclization of the allenylphosphonate
derivatives leading to a furan framework: Brel, V. K. Synthesis 2001,
1539-1545.
10.1021/jo0488614 CCC: $27.50 © 2004 American Chemical Society
Published on Web 09/04/2004
J . Org. Chem. 2004, 69, 6867-6873
6867

Mukai et al.
TABLE 1. Rin g Closu r e of 6a
TABLE 2. Rin g Closu r e of 8a
entry
n
product
yield (%)
product
yield (%)
entry
n
product
yield (%)
product
yield (%)
1
2
3
4
1
2
3
4
6a
6b
6c
6d
82
71
70
74
7a
7b
7c
b
81
89
78
1
2
3
4
1
2
3
4
8a
8b
8c
8d
81
77
83
76
9a
9b
9c
9d
98
71
94
81d
a
a
Reaction conditions: (a) Ph2PCl, Et3N, THF, -78 °C; (b) PPTS,
Reaction conditions: (a) (EtO)2PCl, Et3N, CHCl3, reflux; (b)
PPTS, MeOH, rt; (c) tBuOK, tBuOH, 30 °C; (d) the reaction mixture
was heated at 60 °C. When the reaction was carried out at rt, 9d
was obtained in 75% yield.
t
b
MeOH, rt; (c) tBuOK, BuOH, 30 °C. The reaction mixture was
heated at 60 °C, and 2-octyne-1,8-diol was obtained in 63% yield.
Resu lts a n d Discu ssion
(20 min) to give 9d in 81% yield (entry 4). Interestingly,
consecutive retro-[2,3]-sigmatropic rearrangement and
hydrolysis, which occurred with the allenylphosphine
oxide 6d , was not observed even at 60 °C. These results
indicate that the endo-mode ring-closing reaction of the
allenylphosphonates 8 could be used to prepare five- to
eight-membered oxacycles.
The known propargyl alcohol 12 was treated with
chlorodiphenylphosphine (Ph2PCl) in THF at -78 °C in
the presence of Et3N to give the corresponding alle-
nylphosphine oxides with a siloxy group, which were
subsequently exposed to PPTS in MeOH at room tem-
t
perature to give 6 (Table 1). Treatment of 6a with BuOK
To summarize the present and previous results,2 the
behavior of allenyl sulfoxides 2 under endo-mode ring-
closing conditions is quite similar to that of allenylphos-
phine oxides 6, resulting in the formation of five- to
seven-membered oxacycles. These procedures were not
suitable for the construction of medium-sized oxacycles.
In contrast to these results, both the starting allenyl
sulfone 3 and the allenylphosphonates 8 were easily
transformed into five- to eight-membered oxacycles.
The next phase of this program involved the applica-
tion of the endo-mode ring-closing reaction to the con-
struction of medium-sized oxacycles with an additional
double bond, such as the dihydrooxocin and tetrahy-
drooxonin frameworks. The starting allenes 12 were
prepared as follows. Hydrogenation of compound 1b with
nickel boride (Ni2B)10 gave the allyl alcohol derivative
which was subsequently treated with TBDPSCl and
PPTS to afford 1011 in 81% overall yield. Oxidation of 10
was followed by dibromoolefination and treatment with
base to leave the acetylide,12 which was quenched by
paraformaldehyde to furnish 11 in 73% yield. Upon
exposure to PhSCl at -78 °C, 11 underwent the forma-
tion of sulfenic ester and [2,3]-sigmatropic rearrangement
to give, after desilylation, 12a in 85% yield. A similar
protocol with Ph2PCl and (EtO)2PCl instead of PhSCl
provided 12c (83%) and 12d (82%), respectively. In the
preparation of the sulfonyl derivative 12b, the resulting
sulfoxide, derived from the reaction of 11 with PhSCl,
t
in BuOH at 30 °C for 10 min (the previously optimized
conditions for allenyl sulfoxides 22) effected endo-mode
ring closure to produce the dihydrofuran derivative 7a
in 81% yield (entry 1). The dihydropyran and tetrahy-
drooxepin frameworks 7b and 7c were also constructed
under similar conditions in acceptable yields (89% and
78%, respectively) (entries 2 and 3). However, exposure
of 6d (n ) 4) to standard basic conditions led to complete
recovery of the starting material. Heating the reaction
mixture at 60 °C furnished 2-octyne-1,8-diol2 in 63%
yield, which was presumably formed through the retro
[2,3]-sigmatropic rearrangement of 6d , followed by hy-
drolysis.9 Thus, the endo-mode ring-closing reaction of
allenylphosphine oxides 6 could be used to prepare five-
to seven-membered oxacycles, but not medium-sized
oxacycles.
We next investigated the ring-closing reaction of phos-
phonate derivatives 8. According to the procedure de-
scribed for the conversion of 1 to 6, propargyl alcohol 1a
was treated with chlorodiethoxyphosphine [(EtO)2PCl] in
THF at room temperature. However, no reaction took
place and 1a was completely recovered intact. After
several reaction conditions were screened, CHCl3 was
found to be a suitable solvent for this transformation.
Thus, a solution of 1a and (EtO)2PCl in CHCl3 was
refluxed for 1 h to give, after desilylation, 8a in 81% yield.
Similarly, 8b-d were prepared in acceptable yields
t
(Table 2). Exposure of 8a to BuOK at 30 °C for 10 min
13
was oxidized with (NH4)6Mo7O24/H2O2 and then desily-
produced the ring-closed product 9a in 98% yield (entry
1). The six- and seven-membered oxacycles 9b and 9c
were also formed through an endo-mode process from the
corresponding allenylphosphonates 8b and 8c (entries 2
and 3). Furthermore, the endo-mode ring-closing reaction
of 8d proceeded at 30 °C for 6 h to give the eight-
membered oxacycle 9d in 75% yield. The reaction time
(6 h) was significantly shortened with heating at 60 °C
lated to give 12b in 79% yield.
With the desired four allyl alcohol derivatives 12 in
hand, the ring-closing reaction was then carried out.
According to the standard basic conditions, 12a was
(10) Brown, C. A.; Ahuja, V. K. J . Org. Chem. 1973, 38, 2226-2230.
(11) Hayashi, N.; Noguchi, H.; Tsuboi, S. Tetrahedron 2000, 56,
7123-7137.
(12) Corey, E. J .; Fuchs, P. L. Tetrahedron Lett. 1972, 3769-3772.
(13) Schultz, H. S.; Freyermuth, H. B.; Buc, S. R. J . Org. Chem.
1963, 28, 1140-1142.
(9) A similar result was observed when the corresponding allenyl
sulfoxide 2 (n ) 4) was exposed to BuOK in tBuOH at 60 °C.
t
6868 J . Org. Chem., Vol. 69, No. 20, 2004

Base-Catalyzed Endo-Mode Cyclization of Allenes
SCHEME 2 a
SCHEME 3 a
a
Reaction conditions: (a) Ni(OAc)2, H2, NaBH4, H2N(CH2)2NH2,
NaOH, EtOH, rt; (b) TBDPSCl, imid, DMF, 0 °C to rt; (c) PPTS,
MeOH-THF (1:1), rt, (81%); (d) SO3‚Py, DMSO, Et3N, CH2Cl2, 0
°C to rt; (e) PPh3, CBr4, CH2Cl2, -20 °C; (f) nBuLi, (HCHO)n, THF,
-78 °C to rt, (73%); (g) PhSCl, Et3N, THF, -78 °C; (h) 10% HCl,
MeOH, rt; (i) H2O2, (NH4)6Mo7O24‚4H2O, EtOH, 0 °C; (j) Ph2PCl,
Et3N, THF, -78 °C; (k) (EtO)2PCl, Et3N, CHCl3, reflux; (l) tBuOK,
tBuOH, 30 °C.
a
Reaction conditions: (a) PPh3, I2, imid, 0 °C to rt, (quant); (b)
THF-DMPU, LiCtCCH2OTBDMS, -78 °C to rt; (c) PPTS,
MeOH-THF (1:1), rt, (61%); (d) PhSCl, Et3N, THF, -78 °C; (e)
H2O2, (NH4)6Mo7O24‚4H2O, EtOH, 0 °C; (f) 10% HCl, MeOH, rt;
t
t
(g) (EtO)2PCl, Et3N, CHCl3, reflux; (h) BuOK, BuOH, 30 °C; (i)
tBuOK, BuOH, 60 °C.
t
t
t
treated with BuOK in BuOH at 30 °C to give the 5,6-
dihydro-2H-oxocin 13a in 61% yield. Similar treatment
of 12c produced 13c in 85% yield. These results are in
contrast to those observed in the ring-closing reaction of
sulfoxides 2 and phosphine oxides 6, in which the eight-
membered products were not detected. The sulfonyl and
phosphonate derivatives 12b and 12d provided the
corresponding dihydrooxocin derivatives 13b and 13d in
high yields, as expected. Thus, the introduction of a cis
double bond to the starting allenes facilitated the forma-
tion of an eight-membered oxacyclic ring system via the
endo-mode ring closure.
ring-closing reaction and the thermal [3,3]-sigmatropic
rearrangement to give 17a 15 in 76% yield.
To prevent an unfavorable [3,3]-sigmatropic rearrange-
ment of the resulting 4,5,6,9-tetrahydrooxonin skeleton,
we focused on preparing 2,3,6,7-tetratahydrooxonins. The
Wittig reaction of the aldehyde 1917 with the alkyliden-
etriphenylphosphorane,18 derived from 20, was followed
by desilylation to give 21 in 83% yield. Introduction of a
hydroxymethyl group at the triple bond terminus was
n
realized by exposure of 21 to BuLi and paraformalde-
hyde to give 22 in 93% yield. According to the procedure
described for the preparation of allenes 12 from 11 in
Scheme 2, compound 22 was subjected to [2,3]-sigmat-
ropic rearrangement with a proper reagent to produce,
after deprotection, the corresponding allenes 23 in good
Based on the observations in Scheme 2, we expected
that we could readily obtain the 4,5,6,9-tetrahydrooxonin
skeleton (nine-membered oxacycle). Thus, the starting
allenyl sulfone 16a and allenylphosphonate 16b with an
allyl alcohol moiety were prepared by conventional means
t
yields. The standard basic conditions (tBuOK in BuOH
at 30 °C) effected the rapid endo-mode ring closure of the
sulfoxide derivative 23a to furnish 2,3,6,7-tetrahydro-9-
methyl-8-phenylsulfinyloxonin (24a ) in 71% yield as a
single isomer. Similarly, treatment of 23c and 23d with
tBuOK produced the corresponding nine-membered ox-
acyclic frameworks 24c and 24d , respectively, in accept-
able yields (Scheme 4). In the case of the sulfonyl
derivative 24b, the endo-mode ring-closing reaction
proceeded as expected to furnish the ring-closed products
in 66% yield as a mixture of 24b and its isomer 24b′ with
an exo-methylene moiety in a ratio of ca. 2:1.19 This result
was different from those observed in the ring-closing
t
t
(Scheme 3). Treatment of 16b with BuOK in BuOH at
30 °C gradually produced the new product,14 but the
reaction rate was too slow for the starting material to
disappear completely. When the reaction mixture was
heated at 60 °C, the starting material completely disap-
peared and the unexpected cyclopentane derivative 17b15
was obtained in 77% yield instead of the expected
tetrahydrooxonin 18 (R ) PO(OEt)2). Molecular model
considerations of compound 18 provided clues to better
understand the production of the cyclopentane skeleton.
The formation of 17b from 16b could be interpreted in
terms of the initial formation of the 4,5,6,9-tetrahy-
drooxonin 18 (R ) PO(OEt)2) via the endo-mode ring-
closing reaction, which would spontaneously undergo
thermal [3,3]-sigmatropic rearrangement16 (see con-
former 18′), resulting in the exclusive formation of the
(16) For [3,3]-sigmatropic rearrangement of the acyclic vinyl ether
derivatives, which have an allyl moiety with an electron-withdrawing
group, see: (a) Cookson, R. C.; Gopalan, R. J . Chem. Soc., Chem.
Commun. 1978, 608. (b) Denmark, S. E.; Harmata, M. A. J . Am. Chem.
Soc. 1982, 104, 4972-4974. (c) Denmark, S. E.; Marlin, J . E. J . Org.
Chem. 1991, 56, 1003-1013.
t
cyclopentane framework. Upon exposure to BuOK in
tBuOH at 30 °C, 16a underwent a similar consecutive
(17) Staab, H. A.; Meissner, U. E.; Weinacht, W.; Gensler, A. Chem.
Ber. 1979, 112, 3895-3906.
(18) Schow, S. R.; McMorris, T. C. J . Org. Chem. 1979, 44, 3760-
(14) The newly formed product was identified as 17b.
(15) The stereochemistry of compound 17 was undetermined. On
the basis of molecular model considerations, we tentatively assumed
that the relative stereochemistry between the acetyl and vinyl groups
was cis.
3765.
(19) Both isomers 24b and 24b′ could be isolated by chromatogra-
phy. Compounds 24b and 24b′ were independently exposed to the ring-
closing conditions to give a similar mixture of 24b and 24b′ in a ratio
of ca. 2:1.
J . Org. Chem, Vol. 69, No. 20, 2004 6869

Mukai et al.
SCHEME 4 a
8.5 Hz), 129.2 (J C-P ) 12.2 Hz), 95.6 (J C-P ) 100.1 Hz), 77.1
(J C-P ) 13.4 Hz), 61.8 (J C-P ) 3.7 Hz), 32.9 (J C-P ) 4.9 Hz);
MS m/z 284 (M+, 33); HRMS calcd for C17H17O2P 284.0966,
found 284.0957. Anal. Calcd for C17H17O2P: C, 71.82; H, 6.03.
Found: C, 71.52; H, 6.05.
Gen er a l P r oced u r e for Rin g Closu r e of Allen ylp h os-
t
p h in e Oxid es 6. To a solution of 6 (2.00 × 10-1 mmol) in -
t
BuOH (2.0 mL) was added BuOK (3.00 × 10-1 mmol) at 30
°C. After being stirred for 10 min, the reaction mixture was
diluted with water and extracted with AcOEt. The extract was
washed with water and brine, dried, and concentrated to
dryness. Chromatography of the residue with AcOEt afforded
the corresponding oxacycles 7. Chemical yields are sum-
marized in Table 1.
3-(Diph en ylph osph in yl)-2-m eth yl-4,5-dih ydr ofu r an (7a):
colorless needles; mp 101-102 °C (Et2O); IR 1628 cm-1 1H
;
NMR δ 7.74-7.40 (10H, m), 4.38 (2H, t, J ) 9.6 Hz), 2.73-
2.60 (2H, m), 1.97-1.92 (3H, m); 13C NMR δ 168.6 (J C-P
)
19.5 Hz), 133.3 (J C-P ) 108.7 Hz), 131.5 (J C-P ) 2.5 Hz), 131.3
(J C-P ) 9.8 Hz), 128.4 (J C-P ) 12.2 Hz), 96.1 (J C-P ) 123.3
Hz), 69.8 (J C-P ) 11.0 Hz), 33.2 (J C-P ) 9.7 Hz), 13.8; MS m/z
284 (M+, 100); HRMS calcd for C17H17O2P 284.0966, found
284.0961. Anal. Calcd for C17H17O2P: C, 71.82; H, 6.03.
Found: C, 71.50; H, 5.97.
a
Reaction conditions: (a) KHMDS, THF, -78 °C; (b) K2CO3,
MeOH, rt, (83%); (c) nBuLi, (HCHO)n, THF, -78 °C to rt, (93%);
(d) PhSCl, Et3N, THF, -78 °C; (e) p-TsOH, MeOH, rt; (f) H2O2,
(NH4)6Mo7O24‚4H2O, EtOH, 0 °C; (g) Ph2PCl, Et3N, THF, -78 °C;
(h) (EtO)2PCl, Et3N, CHCl3, reflux; (i) BuOK, BuOH, 30 or 60
°C.
t
t
5-(Dip h en ylp h osp h in yl)-6-m eth yl-3,4-d ih yd r o-2H-p y-
r a n (7b): colorless oil; IR 1614 cm-1 1H NMR δ 7.72-7.44
;
(10H, m), 4.08-4.05 (2H, m), 2.03 (3H, d, J ) 1.3 Hz), 1.83-
1.76 (4H, m); 13C NMR δ 164.7 (J C-P ) 18.3 Hz), 133.8 (J C-P
) 105.0 Hz), 131.6 (J C-P ) 9.8 Hz), 131.4 (J C-P ) 2.4 Hz), 128.4
reaction of 23a ,c,d , in which ring-closed products 24a ,c,d
possessing an endo-olefin moiety were isolated as a sole
isolable product. Thus, a new procedure for constructing
the 2,3,6,7-tetrahydrooxonin skeleton was developed via
the endo-mode ring-closing reaction of allenes.
(J C-P ) 11.0 Hz), 96.7 (J C-P ) 112.3 Hz), 66.3, 24.3 (J C-P
)
9.7 Hz), 22.1 (J C-P ) 8.5 Hz), 20.6 (J C-P ) 3.7 Hz); MS m/z
298 (M+, 92); HRMS calcd for C18H19O2P 298.1123, found
298.1123. Anal. Calcd for C18H19O2P‚1/2H2O: C, 70.35; H, 6.56.
Found: C, 70.38; H, 6.73.
In summary, we have developed a reliable and efficient
procedure for constructing various types of oxacycles via
an endo-mode ring-closing reaction. Allenyl sulfoxide and
allenylphosphine oxide derivatives gave five- to seven-
membered oxacycles. On the other hand, allenyl sulfone
and allenylphosphonate congeners produced the corre-
sponding five- to eight-membered oxacycles. In addition,
the introduction of a cis double bond to the alkyl side
chain of the starting allenes made possible the easy
formation of medium-sized oxacycles with an additional
double bond, such as the dihydrooxocin and tetrahy-
drooxonin frameworks, regardless of the electron-with-
drawing group at the C1-position of the starting allenes.
The application of this simple and efficient method to the
synthesis of bioactive compounds is now in progress.
3-(Diph en ylph osph in yl)-2-m eth yl-4,5,6,7-tetr ah ydr oox-
ep in (7c): colorless needles; mp 101-102 °C (Et2O); IR 1607
cm-1; 1H NMR δ 7.80-7.40 (10H, m), 4.15 (2H, t, J ) 5.9 Hz),
2.14-2.00 (5H, m), 1.90-1.78 (2H, m), 1.64-1.50 (2H, m); 13
C
NMR δ 171.8 (J C-P ) 19.6 Hz), 133.8 (J C-P ) 105.0 Hz), 131.6
(J C-P ) 9.8 Hz), 131.4, 128.5 (J C-P ) 12.2 Hz), 107.7 (J C-P
)
103.7 Hz), 71.5, 29.6, 29.3 (J C-P ) 9.8 Hz), 24.5 (J C-P ) 7.3
Hz), 21.8; MS m/z 312 (M+, 83); HRMS calcd for C19H21O2P
312.1279, found 312.1271. Anal. Calcd for C19H21O2P: C, 73.06;
H, 6.78. Found: C, 73.12; H, 6.89.
3-(Diet h oxyp h osp h in yl)-3,4-p en t a d ien -1-ol (8a ). To a
solution of 1a (49.8 mg, 2.32 × 10-1 mmol) and Et3N (0.10 mL,
0.72 mmol) in CHCl3 (2.0 mL) was gradually added a solution
of diethyl chlorophosphite (90%, 121 mg, 0.70 mmol) in CHCl3
(1.0 mL) at room temperature. The reaction mixture was
refluxed for 1 h and then diluted with water and extracted
with AcOEt. The extract was washed with water and brine,
dried, and concentrated to dryness. To a solution of the crude
product in MeOH (2.0 mL) was added PPTS (5.8 mg, 2.3 ×
10-2 mmol) at room temperature, and the mixture was stirred
overnight. MeOH was evaporated off, and the residue was
taken up in AcOEt, washed with brine, dried, and concentrated
to dryness. Chromatography of the residue with AcOEt gave
Exp er im en ta l Section
3-(Dip h en ylp h osp h in yl)-3,4-p en ta d ien -1-ol (6a ). To a
solution of 5-(tert-butyldimethylsiloxy)-2-pentyn-1-ol (1a ) (215
mg, 1.00 mmol) and Et3N (0.42 mL, 3.1 mmol) in THF (10 mL)
was gradually added a solution of chlorodiphenylphosphine
(663 mg, 3.00 mmol) in THF (1.0 mL) at -78 °C. After being
stirred for 30 min at the same temperature, the reaction was
quenched by addition of water, and the resulting mixture was
extracted with AcOEt. The extract was washed with water and
brine, dried, and concentrated to dryness. To a solution of the
crude product in MeOH (10 mL) was added PPTS (25 mg, 0.10
mmol) at room temperature, and the mixture was stirred
overnight. MeOH was evaporated off, and the residue was
taken up in AcOEt, which was washed with water and brine,
dried, and concentrated to dryness. Chromatography of the
residue with AcOEt gave 6a (235 mg, 82%) as colorless
needles: mp 107.5-108 °C (hexane-AcOEt); IR 3337, 1965,
1935 cm-1; 1H NMR δ 7.79-7.70 (4H, m), 7.58-7.42 (6H, m),
4.68 (2H, dt, J ) 11.2, 2.3 Hz), 3.80 (2H, t, J ) 5.3 Hz), 2.59-
2.48 (2H, m); 13C NMR (acetone-d6) δ 211.6 (J C-P ) 7.3 Hz),
8a (41.2 mg, 81%) as a colorless oil: IR 3398, 1965, 1936 cm-1
;
1H NMR (C6D6) δ 4.62 (2H, dt, J ) 13.2, 2.6 Hz), 4.50 (1H,
brs), 4.06-3.83 (6H, m), 2.66-2.47 (2H, m), 1.06 (6H, t, J )
6.9 Hz); 13C NMR (C6D6) δ 212.2 (J C-P ) 6.1 Hz), 91.3 (J C-P
)
188.0 Hz), 76.1 (J C-P ) 15.9 Hz), 62.6 (J C-P ) 6.1 Hz), 61.3
(J C-P ) 6.1 Hz), 32.7 (J C-P ) 6.1 Hz), 16.3 (J C-P ) 6.1 Hz);
MS m/z 220 (M+, 3.2); HRMS calcd for C9H17O4P 220.0865,
found 220.0857. Anal. Calcd for C9H17O4P‚1/2H2O: C, 47.16;
H, 7.92. Found: C, 47.20; H, 7.98.
Rin g Closu r e of Allen ylp h osp h on a tes 8. According to
the procedure described for ring closure of 6, compounds 8 was
exposed to the standard ring-closing conditions. Chemical
yields of oxacycles 9 are summarized in Table 2.
7-(Diet h oxyp h osp h in yl)-8-m et h yl-3,4,5,6-t et r a h yd r o-
1
133.0 (J C-P ) 104.9 Hz), 132.7 (J C-P ) 2.4 Hz), 132.4 (J C-P
)
2H-oxocin (9d ): colorless oil; IR (neat) 1634 cm-1; H NMR
6870 J . Org. Chem., Vol. 69, No. 20, 2004

Base-Catalyzed Endo-Mode Cyclization of Allenes
(C6D6) δ 4.06-3.82 (4H, m), 3.60 (2H, t, J ) 5.3 Hz), 2.69-
2.51 (2H, m), 2.34 (3H, d, J ) 1.3 Hz), 1.69-1.56 (2H, m),
1.50-1.20 (4H, m), 1.07 (6H, t, J ) 7.1 Hz); 13C NMR (C6D6)
δ 165.3 (J C-P ) 29.3 Hz), 115.8 (J C-P ) 181.9 Hz), 70.9 (J C-P
(2H, m), 2.22-2.05 (4H, m), 1.63 (1H, t, J ) 6.3 Hz), 1.06 (9H,
s); 13C NMR δ 135.5, 133.7, 130.6, 129.6 128.6, 127.6, 85.6,
78.8, 60.3, 51.3, 26.8, 26.6, 19.1, 18.9; FABMS m/z 379 (M+
+
1, 8.5). Anal. Calcd for C24H30O2Si: C, 76.14; H, 7.99. Found:
C, 75.98; H, 8.12.
) 2.4 Hz), 60.9 (J C-P ) 4.9 Hz), 30.1, 28.6, 27.5, 26.4 (J C-P
)
7.4 Hz), 16.9, 16.4 (J C-P ) 6.1 Hz); MS m/z 262 (M+, 32); HRMS
calcd for C12H23O4P 262.1334, found 262.1340. Anal. Calcd for
(Z)-6-(P h en ylsu lfin yl)-2,6,7-octa tr ien -1-ol (12a ). To a
solution of 11 (105 mg, 2.77 × 10-1 mmol) and Et3N (0.12 mL,
0.86 mmol) in THF (2.8 mL) was gradually added a solution
of benzenesulfenyl chloride (60.7 mg, 4.19 × 10-1 mmol) in
THF (1.0 mL) at -78 °C. After the mixture was stirred for 2
h, the reaction was quenched by addition of water, and the
mixture was extracted with AcOEt. The extract was washed
with water and brine, dried, and concentrated to dryness. The
residual oil was passed through a short pad of silica gel with
CH2Cl2 to afford the crude sulfoxide. Aqueous HCl (10%, 1.0
mL) was added to a solution of the crude sulfoxide in MeOH
(3.0 mL) at room temperature. After being stirred for 1 h, the
reaction mixture was diluted with water and extracted with
AcOEt. The extract was washed with water and brine, dried,
and concentrated to dryness. Chromatography of the residue
with hexane-AcOEt (2:1) gave 12a (58.8 mg, 85%) as a
colorless oil: IR 3429, 1969, 1944 cm-1; 1H NMR δ 7.66-7.40
(5H, m), 5.64-5.49 (1H, m), 5.43-5.17 (3H, m), 4.14-3.97 (2H,
m), 2.34-1.84 (4H, m); 13C NMR δ 205.8, 143.3, 130.9, 130.6,
129.9, 129.1, 124.5, 112.2, 82.4, 58.3, 25.4, 23.0; MS m/z 248
(M+, 3.6); HRMS calcd for C14H16O2S 248.0871, found 248.0872.
C
12H23O4P: C, 54.95; H, 8.84. Found: C, 54.82; H, 8.93.
(Z)-6-(ter t-Bu t yld ip h en ylsiloxy)-4-p en t en -1-ol (10).11
NaBH4 (167 mg, 4.41 mmol) was added to a solution of EtOH
(4.0 mL) containing 2 N aqueous NaOH (0.2 mL) at room
temperature. After being stirred for 10 min, the mixture was
filtered through a Celite pad. The filtrate (0.26 mL) was then
added dropwise to a suspension of Ni(OAc)2‚4H2O (55.6 mg,
2.23 × 10-1 mmol) in EtOH (5.0 mL) with vigorous stirring
under a hydrogen atmosphere. A solution of ethylenediamine
(0.04 mL) and 1b (189 mg, 8.27 × 10-1 mmol) in EtOH (2.0
mL) was added to a solution of Ni2B, thus formed, in EtOH.
After being stirred for 1 h, the mixture was diluted with water
and extracted with AcOEt. The extract was washed with water
and brine, dried, and concentrated to dryness. The residue was
passed through a short pad of silica gel with hexane-AcOEt
(4:1) to afford the crude alkene (178 mg). To a solution of the
crude alkene (165 mg) and imidazole (117 mg, 1.72 mmol) in
DMF (1.0 mL) was added TBDPSCl (236 mg, 8.58 × 10-1
mmol) at 0 °C, and the mixture was warmed to room temper-
ature. The mixture was stirred for 2 h at ambient temperature,
diluted with water, and extracted with Et2O. The extract was
washed with water and brine, dried, and concentrated to
dryness. To a solution of the crude product in MeOH-THF
(1:1, 7.0 mL) was added PPTS (18 mg, 7.2 × 10-2 mmol) at
room temperature, and the mixture was stirred overnight. The
solvent was evaporated off, and the resulting residue was
taken up in AcOEt, which was washed with water and brine,
dried, and concentrated to dryness. Chromatography of the
residue with hexane-AcOEt (4:1) gave 10 (227 mg, 81%) as a
colorless oil: 1H NMR δ 7.74-7.65 (4H, m), 7.48-7.35 (6H,
m), 5.64 (1H, dtt, J ) 10.9, 6.3, 1.3 Hz), 5.51-5.38 (1H, m),
4.26 (2H, dd, J ) 6.3, 0.7 Hz), 3.57 (2H, t, J ) 6.3 Hz), 2.01
(Z)-6-(P h en ylsu lfon yl)-2,6,7-oct a t r ien -1-ol (12b ). Ac-
cording to the procedure for the preparation of 12a , 11 (105
mg, 2.77 × 10-1 mmol) was converted the corresponding
sulfoxide with a siloxy group. (NH4)6Mo7O24‚4H2O (620 mg,
5.00 × 10-1 mmol) and 30% H2O2 (1.4 mL) were combined at
0 °C and stirred for 15 min. This newly adjusted bright yellow
solution was added dropwise to a solution of the crude
sulfoxide in EtOH (2.5 mL) at 0 °C. After being stirred for 2
h, the reaction mixture was diluted with water and extracted
with Et2O. The extract was washed with brine, dried, and
concentrated to dryness. Aqueous HCl (10%, 1.0 mL) was
added to a solution of the crude product in MeOH (2.0 mL) at
room temperature. After being stirred for 2.5 h, the reaction
mixture was diluted with water and extracted with AcOEt,
which was washed with water and brine, dried, and concen-
trated to dryness. Chromatography of the residue with CH2-
Cl2-AcOEt (8:1) gave 12b (57.8 mg, 79%) as a colorless oil:
(2H, qd, J ) 7.3, 1.3 Hz), 1.62-1.48 (3H, m), 1.05 (9H, s); 13
C
NMR δ 135.6, 133.7, 130.7, 129.6 129.5, 127.6, 61.9, 60.0, 32.0,
26.8, 23.6, 19.1.
(Z)-8-(ter t-Bu tyld ip h en ylsiloxy)-6-octen -2-yn -1-ol (11).
To a solution of 10 (1.12 g, 3.16 mmol), DMSO (2.8 mL), and
Et3N (2.2 mL, 16 mmol) in CH2Cl2 (16 mL) was added SO3‚Py
(2.25 g, 14.1 mmol) at 0 °C. The mixture was warmed to room
temperature and stirred for 3 h. The reaction was quenched
by addition of saturated aqueous NH4Cl, and the mixture was
extracted with AcOEt. The extract was washed with water and
brine, dried, and concentrated to leave the crude aldehyde. To
a solution of PPh3 (3.30 g, 12.6 mmol) in CH2Cl2 (9.0 mL) was
added CBr4 (2.09 g, 6.30 mmol) at 0 °C, and the reaction
mixture was stirred for 5 min. A solution of the crude aldehyde
in CH2Cl2 (3.0 mL) was then added to a solution of the ylide
at -20 °C. The mixture was stirred overnight, diluted satu-
rated aqueous NaHCO3, and extracted with CH2Cl2. The
extract was washed with water and brine, dried, and concen-
trated to dryness. The residue was passed through a short pad
of silica gel with hexane-AcOEt (20:1) to afford the crude
dibromo derivative. To a solution of the dibromo derivative in
IR 3611, 3533, 1969, 1940 cm-1 1H NMR δ 7.93-7.78 (2H,
;
m), 7.67-7.45 (3H, m), 5.69-5.25 (4H, m) 4.11 (2H, dd, J )
6.9, 0.7 Hz) 2.40-2.10 (4H, m); 13C NMR δ 207.9, 139.9, 133.5,
130.2, 130.0, 129.1, 128.1, 112.4, 84.6, 58.3, 26.7, 25.4; MS m/z
264 (M+, 1.0); HRMS calcd for C14H16O3S 264.0820, found
264.0815.
Rin g Closu r e of Allen e Der iva tives 12. According to the
procedure described for ring closure of 6, compounds 12 was
exposed to the standard ring-closing conditions. Chemical
yields of oxacycles 13 are summarized in Scheme 2.
8-Me t h yl-7-(p h e n ylsu lfin yl)-5,6-d ih yd r o-2H -oxocin
1
(13a ): colorless oil; IR 1620 cm-1; H NMR δ 7.57-7.35 (5H,
m), 5.78-5.50 (2H, m), 4.79 (1H, dd, J ) 13.5, 7.6 Hz), 4.56
(1H, dd, J ) 13.5, 6.9 Hz), 2.69-2.21 (6H, m), 1.83-1.57 (1H,
m); 13C NMR δ 158.8, 144.0, 136.9, 130.0, 128.7, 124.5, 122.6,
120.4, 65.3, 30.1, 20.6, 19.1; MS m/z 248 (M+, 14); HRMS calcd
for C14H16O2S 248.0871, found 248.0873.
n
THF (16 mL) was added BuLi (1.39 M in hexane, 5.7 mL, 7.9
8-Me t h yl-7-(p h e n ylsu lfon yl)-5,6-d ih yd r o-2H -oxocin
mmol) at -78 °C. The reaction mixture was stirred for 30 min,
and paraformaldehyde (280 mg, 9.40 mmol) was added to the
resulting solution of the acetylide. The mixture was warmed
to room temperature and stirred overnight. The reaction was
quenched by addition of saturated aqueous NH4Cl, and the
mixture was extracted with AcOEt. The extract was washed
with water and brine, dried, and concentrated to dryness.
Chromatography of the residue with hexane-AcOEt (6:1) gave
11 (869 mg, 73%) as a colorless oil: IR 3609 cm-1; 1H NMR δ
7.73-7.68 (4H, m), 7.48-7.36 (6H, m), 5.74-5.64 (1H, m),
5.51-5.41 (1H, m), 4.28 (2H, dd, J ) 6.3, 1.0 Hz), 4.20-4.17
1
(13b): colorless oil; IR 1607 cm-1; H NMR δ 7.87-7.73 (2H,
m), 7.61-7.42 (3H, m), 5.92 (1H, dt, J ) 10.9, 5.6 Hz), 5.55
(1H, dtt, J ) 10.9, 6.6, 1.3 Hz), 4.69 (2H, d, J ) 6.6 Hz), 2.61-
2.46 (2H, m), 2.77 (2H, t, J ) 6.3 Hz), 2.20 (3H, s); 13C NMR
δ 163.8, 142.7, 136.1, 132.5, 128.9, 126.8, 122.6, 120.8, 67.4,
29.1, 26.9, 19.8; MS m/z 264 (M+, 32); HRMS calcd for
C
C
14H16O3S 264.0820, found 264.0817. Anal. Calcd for
14H16O3S: C, 63.61; H, 6.10. Found: C, 63.34; H, 6.11.
(Z)-1-(ter t-Bu tyld ip h en ylsiloxy)-6-iod o-2-h exen e (14).
To a solution of 10 (366 mg, 1.03 mmol) in CH2Cl2 (10 mL)
J . Org. Chem, Vol. 69, No. 20, 2004 6871

Mukai et al.
were added PPh3 (325 mg, 1.24 mmol) and imidazole (84.3 mg,
1.24 mmol). I2 (310 mg, 1.24 mmol) was then added to the
reaction mixture at 0 °C, and the mixture was warmed to room
temperature. After being stirred for 1 h, the reaction mixture
was diluted with saturated aqueous Na2S2O3 and extracted
with CH2Cl2. The extract was washed with water and brine,
dried, and concentrated to dryness. Chromatography of the
residue with hexane-AcOEt (10:1) gave 14 (479 mg, quant)
as a colorless oil: 1H NMR δ 7.74-7.66 (4H, m), 7.48-7.34
(6H, m), 5.67 (1H, dtt, J ) 11.2, 6.3, 1.7 Hz), 5.35 (1H, dtt, J
) 11.2, 7.3, 1.3 Hz), 4.28 (2H, dd, J ) 6.3, 1.3 Hz), 3.07 (2H,
t, J ) 6.9 Hz), 2.03-1.90 (2H, m), 1.85-1.71 (2H, m), 1.05 (9H,
s); 13C NMR δ 135.6, 133.7, 130.7, 129.6, 128.5, 127.6, 60.2,
33.2, 28.3, 26.8, 19.1, 6.1; FABMS m/z 464 (M+, 1.1); HRMS
calcd for C22H29IOSi 464.1032, found 464.1039. Anal. Calcd
for C22H29IOSi: C, 56.89; H, 6.29. Found: C, 56.51; H, 6.30.
through a short pad of silica gel with hexane-AcOEt (20:1) to
give the crude enyne. K2CO3 (690 mg, 5.00 mmol) was added
to a solution of the crude enyne in MeOH (13 mL) at room
temperature. The mixture was stirred for 3 h, and K2CO3 was
filtered off. The filtrate was diluted with saturated NH4Cl and
extracted with AcOEt. The extract was washed with water and
brine, dried, and concentrated to dryness. Chromatography of
the residue with hexane-AcOEt (20:1) gave 21 (434 mg, 83%)
as a colorless oil: IR 3308 cm-1 1H NMR δ 5.59-5.43 (2H,
;
m), 4.62-4.56 (1H, m), 3.92-3.68 (2H, m), 3.55-3.35 (2H, m),
2.42-2.17 (6H, m), 1.95 (1H, t, J ) 2.6 Hz), 1.90-1.43 (6H,
m); 13C NMR δ 129.3, 127.2, 98.5, 83.8, 68.3, 66.7, 62.0, 30.5,
27.9, 26.3, 25.3, 19.4, 18.6; FABMS m/z 208 (M+, 1.5); HRMS
calcd for C13H20O2 208.1463, found 208.1461. Anal. Calcd for
C
13H20O2: C, 74.96; H, 9.68. Found: C, 74.62; H, 9.75.
(Z)-9-[(Tetr a h yd r o-2H-p yr a n -2-yl)oxy]-6-octen -2-yn -1-
ol (22). To a solution of 21 (434 mg, 2.08 mmol) in THF (10
mL) was added BuLi (1.44 M in hexane, 1.70 mL, 2.45 mmol)
(Z)-9-(ter t-Bu tyld ip h en ylsiloxy)-7-n on en -2-yn -1-ol (15).
nBuLi (1.39 M in hexane, 1.20 mL, 1.67 mmol) was added to a
solution of 3-(tert-butyldimethylsiloxy)propyne (325 mg, 1.91
mmol) in THF-DMPU (6:1, 2.8 mL) at -78 °C, and the
reaction mixture was stirred for 1 h. A solution of 14 (592 mg,
1.27 mmol) in THF-DMPU (1.0 mL) was then added to the
solution of acetylide, and the mixture was warmed to room
temperature. After being stirred overnight, the reaction mix-
ture was diluted with water and extracted with AcOEt. The
extract was washed with water and brine, dried, and concen-
trated to dryness. PPTS (32 mg, 0.13 mmol) was added to a
solution of the crude product in MeOH-THF (1:1, 13 mL) at
room temperature, and the mixture was stirred overnight.
MeOH-THF was evaporated off, and the residue was taken
up in AcOEt, which was washed with water and brine, dried,
and concentrated to dryness. Chromatography of the residue
with hexane-AcOEt (4:1) gave 15 (306 mg, 61%) as a colorless
n
at -78 °C. The reaction mixture was stirred for 2 h, and then
paraformaldehyde (188 mg, 6.24 mmol) was added. The
mixture was warmed to room temperature and stirred for 15
h. The reaction mixture was diluted with saturated aqueous
NH4Cl and extracted with AcOEt. The extract was washed
with water and brine, dried, and concentrated to dryness.
Chromatography of the residue with hexane-AcOEt (8:1) gave
1
22 (463 mg, 93%) as a colorless oil: IR 3609, 3422 cm-1; H
NMR δ 5.57-5.42 (2H, m), 4.64-4.57 (1H, m), 4.22 (2H, s)
3.93-3.68 (2H, m), 3.56-3.38 (2H, m), 2.43-2.03 (7H, m),
1.90-1.42 (6H, m); 13C NMR δ 129.5, 127.0, 98.5, 85.1, 78.8,
66.9, 62.0, 50.7, 30.4, 27.7, 26.3, 25.2, 19.2, 18.8; FABMS m/z
238 (M+, 3.4); HRMS calcd for C14H22O3 238.1569, found
238.1566.
2-Meth yl-3-(p h en ylsu lfin yl)-4,5,8,9-tetr a h yd r ooxon in
(24a ). According to the procedure described for ring closure
of 16b, the ring-closing reaction of 23a was performed. The
title compound was obtained in 71% yield as a colorless oil:
IR 1638 cm-1; 1H NMR δ 7.53-7.36 (5H, m), 5.53 (1H, dt, J )
10.6, 8.3 Hz), 5.33-5.18 (1H, m), 3.99 (2H, dd, J ) 5.9, 4.3
Hz), 2.39-1.92 (9H, m); 13C NMR δ 159.0, 143.4, 133.8, 130.0,
128.8, 127.3, 125.5, 124.3, 68.2, 27.2, 25.9, 21.0, 15.7; MS m/z
262 (M+, 2.0); HRMS calcd for C15H18O2S 262.1028, found
262.1032. Anal. Calcd for C15H18O2S: C, 68.67; H, 6.92.
Found: C, 68.30; H, 7.07.
1
oil: IR 3609 cm-1; H NMR δ 7.73-7.64 (4H, m), 7.47-7.34
(6H, m), 5.64 (1H, dtt, J ) 11.2, 6.3, 1.3 Hz), 5.37 (1H, dtt, J
) 11.2, 7.3, 1.7 Hz), 4.30-4.22 (2H, m), 4.14 (2H, t, J ) 2.0
Hz), 2.13 (2H, tt, J ) 7.3, 2.0 Hz), 2.03-1.91 (2H, m), 1.48
(2H, quin, J ) 7.3 Hz), 1.04 (9H, s); 13C NMR δ 135.5, 133.8,
130.1, 129.7, 129.6, 127.6, 85.9, 78.6, 60.2, 51.2, 28.2, 26.8, 26.5,
19.1, 18.0; FABMS m/z 393 (M+ + 1, 4.5); HRMS calcd for
C25H32O2Si 392.2172, found 392.2143. Anal. Calcd for C25H32O2-
Si: C, 76.48; H, 8.22. Found: C, 76.21; H, 8.53.
1-[(1R*,2S*)-1-(Diet h oxyp h osp h in yl)-2-et h en ylcyclo-
p en tyl]eth a n -1-on e (17b). To a solution of 16b (29.9 mg, 1.09
2-Me t h yl-3-(p h e n ylsu lfon yl)-4,5,8,9-t e t r a h yd r ooxo-
n in (24b) a n d 2-Meth ylen e-3-(p h en ylsu lfon yl)-2,3,4,5,8,9-
h exa h yd r ooxon in (24b′). According to the procedure de-
scribed for ring closure of 16b, the ring-closing reaction of 23b
was performed. Title compounds were obtained as a separable
t
t
× 10-1 mmol) in BuOH (5.5 mL) was added BuOK (18.3 mg,
1.63 × 10-1 mmol) at 30 °C. After being stirred for 20 min at
60 °C, the reaction mixture was cooled to room temperature,
diluted with water, and extracted with AcOEt. The extract was
washed with water and brine, dried, and concentrated to
dryness. Chromatography of the residue with AcOEt gave 17b
1
mixture. 24b (44%): a colorless oil; IR 1624 cm-1; H NMR δ
7.89-7.76 (2H, m), 7.61-7.43 (3H, m), 5.59 (1H, dt, J ) 10.6,
7.6 Hz), 5.46 (1H, dt, J ) 10.6, 8.2 Hz), 4.02 (2H, t, J ) 5.3
Hz), 2.46 (2H, t, J ) 6.3 Hz), 2.40 (3H, s), 2.26 (2H, dt, J )
8.2, 6.3 Hz), 2.16 (2H, dt, J ) 7.6, 5.3 Hz); 13C NMR δ 163.4,
142.1, 133.4, 132.7, 128.9, 127.0, 126.2, 124.9, 68.6, 27.2 26.7,
26.2, 16.6; MS m/z 278 (M+, 2.4); HRMS calcd for C15H18O3S
278.0977, found 278.0981. Anal. Calcd for C15H18O3S: C, 64.72;
H, 6.52. Found: C, 64.50; H, 6.63. 24b′ (22%): colorless
(22.9 mg, 77%) as a colorless oil: IR 1701 cm-1 1H NMR δ
;
5.82-5.72 (1H, m), 5.13 (1H, dt, J ) 17.1, 1.0 Hz), 5.03 (1H,
dt, J ) 10.3, 1.0 Hz), 4.19-4.11 (4H, m), 3.20-3.10 (1H, m),
2.52-2.39 (1H, m), 2.27 (3H, s), 2.15-2.02 (1H, m), 2.02-1.93
(1H, m), 1.83-1.69 (2H, m), 1.62-1.53 (1H, m), 1.32 (6H, q, J
) 7.3 Hz); 13C NMR δ 204.7 (J C-P ) 2.4 Hz), 137.7 (J C-P ) 2.4
Hz), 116.4, 64.8 (J C-P ) 136.7 Hz), 62.6 (J C-P ) 7.3 Hz), 62.5
(J C-P ) 8.5 Hz), 49.8 (J C-P ) 2.4 Hz), 32.1 (J C-P ) 7.3 Hz),
30.7, 30.0, 23.5 (J C-P ) 4.9 Hz), 16.4 (J C-P ) 6.1 Hz); MS m/z
274 (M+, 1.7); HRMS calcd for C13H23O4P 274.1334, found
274.1333. Anal. Calcd for C13H23O4P‚1/2H2O: C, 55.11; H, 8.54.
Found: C, 54.86; H, 8.26.
1
needles; mp 108-109 °C (hexane); IR 1641 cm-1; H NMR δ
7.94-7.78 (2H, m), 7.66-7.42 (3H, m), 5.68-5.36 (2H, m), 4.74
(1H, d, J ) 2.3 Hz), 4.60 (1H, dd, J ) 2.3, 1.3 Hz), 4.00-3.83
(2H, m), 3.67 (1H, ddd, J ) 11.9, 5.9, 1.3 Hz), 2.54-1.90 (6H,
m); 13C NMR δ 152.1, 138.0, 133.5, 132.3, 129.2, 128.7, 126.6,
97.4, 70.2, 66.1, 25.7, 24.0, 22.2; MS m/z 278 (M+, 9.6); HRMS
calcd for C15H18O3S 278.0977, found 278.0966. Anal. Calcd for
(Z)-8-[(Tet r a h yd r o-2H -p yr a n -2-yl)oxy]-5-oct en -1-yn e
(21). To a solution of 2018 (3.64 g, 7.50 mmol) in THF (13 mL)
was added KHMDS (0.75 M in toluene, 9.1 mL, 6.8 mmol) at
-78 °C, and the reaction mixture was stirred for 20 min.
Aldehyde 1917 (386 mg, 2.50 mmol) in THF (2.5 mL) was then
added to a solution of the ylide, which was stirred for 15 min.
The reaction mixture was diluted with water and extracted
with AcOEt. The extract was washed with water and brine,
dried, and concentrated to dryness. The residue was passed
C
15H18O3S: C, 64.72; H, 6.52. Found: C, 64.36; H, 6.56.
3-(Diph en ylph osph in yl)-2-m eth yl-4,5,8,9-tetr ah ydr oox-
on in (24c). According to the procedure described for ring
closure of 16b, the ring-closing reaction of 23c was performed.
The title compound was obtained in 68% yield as colorless
needles: mp 129-131 °C (Et2O); IR 1614 cm-1 1H NMR δ
;
7.73-7.37 (10H, m), 5.70-5.46 (2H, m), 4.01 (2H, t, J ) 5.3
6872 J . Org. Chem., Vol. 69, No. 20, 2004

Base-Catalyzed Endo-Mode Cyclization of Allenes
Hz), 2.29-2.04 (7H, m), 1.87-1.76 (2H, m).13C NMR δ 165.1
(J C-P ) 19.6 Hz), 133.7 (J C-P ) 105.0 Hz), 133.3, 131.8 (J C-P
) 9.7 Hz), 131.4 (J C-P ) 2.5 Hz), 128.4 (J C-P ) 10.9 Hz), 126.5,
113.9 (J C-P ) 102.6 Hz), 67.7, 27.9 (J C-P ) 11.0 Hz), 27.4, 26.9
(J C-P ) 2.4 Hz), 17.2 (J C-P ) 2.5 Hz); MS m/z 338 (M+, 45);
HRMS calcd for C21H23O2P 338.1436, found 338.1433. Anal.
Calcd for C21H23O2P: C, 74.54; H, 6.85. Found: C, 74.38; H,
7.03.
(J C-P ) 7.4 Hz), 16.5, 16.3 (J C-P ) 7.3 Hz); MS m/z 274 (M+,
19); HRMS calcd for C13H23O4P 274.1334, found 274.1338.
Ack n ow led gm en t. This work was supported in part
by a Grant-in Aid for Scientific Research from the
Ministry of Education, Culture, Sports, Science and
Technology, J apan, to which we are thankful.
3-(Dieth oxyph osph in yl)-2-m eth yl-4,5,8,9-tetr ah ydr oox-
on in (24d ). According to the procedure described for ring
closure of 16b, the ring-closing reaction of 23d was performed.
The title compound was obtained in 62% yield as a colorless
Su p p or t in g In for m a t ion Ava ila b le: 1H and 13C NMR
spectra for compounds 12a ,b,d , 13a ,d , 16a ,b, 22, 23a -d , and
24d and characterization data for compounds 6b-d , 8b-d ,
9a -c, 12c,d , 13c,d , 16a ,b, 17a , and 23a -d . This material is
available free of charge via the Internet at http://pubs.acs.org.
1
oil: IR 1626 cm-1; H NMR δ 5.73-5.55 (2H, m), 4.13-3.91
(6H, m), 2.41-2.10 (9H, m), 1.30 (6H, t, J ) 6.9 Hz); 13C NMR
δ 164.8 (J C-P ) 30.5 Hz), 133.8, 126.1, 110.8 (J C-P ) 184.3
Hz), 67.5, 61.0 (J C-P ) 4.9 Hz), 27.2, 26.9 (J C-P ) 3.6 Hz), 26.4
J O0488614
J . Org. Chem, Vol. 69, No. 20, 2004 6873