Bistrimethylsilylpropargylic ether: A versatile ambident synthon to access substituted allenyne ethers and α-substituted bispropargylic alcohols

Article abstract of DOI:10.1021/jo0709753

(Chemical Equation Presented) The reactivity of 1,5-bis(trimethylsilyl) propargylic ethers 3 toward bases and electrophiles was investigated. Bispropargylic ethers 4, substituted allenyne ethers 6-8, and α-substituted bispropargylic ethers 9 were prepared

Full text of DOI:10.1021/jo0709753

Bistrimethylsilylpropargylic Ether: A Versatile
Ambident Synthon to Access Substituted
Allenyne Ethers and r-Substituted Bispropargylic
Alcohols
Maude Brossat,† Marie-Pierre Heck,*,† and
Charles Mioskowski†,‡,§
CEA-Saclay, iBiTec-S, SerVice de Chimie Bioorganique et de
Marquage, Baˆt 547, F-91191 Gif sur YVette cedex, France, and
Laboratoire de Synthe`se Bio-organique, Faculte´ de Pharmacie,
UniVersite´ Louis Pasteur, 74 route du Rhin, BP24,
67401 Illkirch, France
marie-pierre.heck@cea.fr
FIGURE 1. 1,5-Bispropargylic synthons.
ReceiVed May 15, 2007
nones,5 enynylcarbene tungsten complexes,7 tetraethynylethenes,8
and tetraethynylallenes.9 Because bispropargylic alcohol 1 is
known to be difficult to handle,10 we have prepared and studied
the corresponding 1,5-bis(trimethylsilyl)propargylic ether 3. To
our surprise, when 3 was submitted to bases and subsequent
addition of electrophiles, either substituted allenyne ethers 6-8
and/or R-substituted bispropargylic derivatives 9 and/or bispro-
pargylic ethers 4 were isolated (Figure 1).
Although many synthetic approaches to allenes11 (base-
catalyzed isomerization of propargyl derivatives,12 Mitsunobu
displacement of propargyl alcohols13), to 1,2-dien-4-ynes,14 to
substituted alkoxyallenes,15 and to silyloxyallenes16 have been
described, to date to our knowledge, no method has been
reported for the preparation of substituted allenyne ethers 6-8.
Moreover, removal of the protecting groups of 9 could give
The reactivity of 1,5-bis(trimethylsilyl)propargylic ethers 3
toward bases and electrophiles was investigated. Bispro-
pargylic ethers 4, substituted allenyne ethers 6-8, and
R-substituted bispropargylic ethers 9 were prepared in good
yields, respectively, by protodesilylation, isomerization, or
metalation/alkylation of bispropargylic protected alcohol 3.
The ambident behavior of metalated synthon 3 was discussed
and rationalized. Removal of the protecting groups of 9 easily
afforded useful R-substituted bispropargylic alcohol.
(6) Detty, M. R.; Luss, H. R. Organometallics 1992, 11, 2157-2162.
(7) Cosset, C.; Del Rio, I.; Pe´ron, V.; Windmu¨ller, B.; Le Bozec, H.
Synlett 1996, 435-436.
(8) Anthony, J.; Boldi, A. M.; Rubin, Y.; Hobi, M.; Gramlich, V.;
Knobler, C. B.; Seiler, P.; Diederich, F. HelV. Chim. Acta 1995, 78, 13-
44.
Although propargylic alcohols and propargylic ethers are
well-known as versatile building blocks in organic synthesis,
there are only a few reports concerning their bispropargylic
homologues.1 Our interest in the development of fatty acids
bearing polyalkyne functionalities led us to investigate the
chemistry of bispropargylic alcohols 1 and 2 and bispropargylic
ethers 3 (Figure 1).
To our knowledge, the rare reactivities of penta-1,4-diyn-3-
ol 12 reported in the literature are its transformation into ketone,3
metallabenzenes,4 dienynes, and vinylallenes.5 The correspond-
ing silylated 1,4-diyn-3-ol6 2 is relatively more documented:
alcohol 2 oxidized into ketone can generate chalcogenapyra-
(9) Lange, T.; van Loon, J.-D.; Tykwinski, R. R.; Schreiber, M.;
Diederich, F. Synthesis 1996, 537-550.
(10) We thank Prof. Jia (see ref 4) for his helpful and warning
comments: a violent explosion may take place during the vacuum distillation
o
of crude 1 if the bath temperature is over 90 C or if the viscosity of the
residue is too high to permit the diffusion of heat. In that case, distillation
should be stopped immediately to avoid accident.
(11) (a) Krause, N.; Hashmi, S. K. Modern Allene Chemistry; Wiley-
VCH: New York, 2004; Vol. 1. (b) Bruneau, C.; Dixneuf, P. H. In
ComprehensiVe Organic Functional Group Transformations; Katritzky, A.
R., Meth-Cohn, O., Rees, C. W., Eds.; Pergamon: New York; 1995; Vol.
2, pp 953-996. (c) Ma, S. Chem. ReV. 2005, 105, 2829-2871.
(12) (a) Pourcelot, G.; Cadiot, P. Bull. Soc. Chem. Fr. 1966, 3016-
3021. (b) Hoff, S.; Bransdma, L.; Arens, J.-F. Recl. TraV. Chim. Pays-Bas
1968, 87, 916-924. (c) Hausherr, A.; Orschel, B.; Scherer, S.; Reissig,
H.-U. Synthesis 2001, 9, 1377-1385. (d) Mereyala, H. B.; Gurraka, S. R.;
Mohan, S. K. Tetrahedron 1999, 55, 11331-11342.
(13) Myers, A. G.; Zheng, B. J. Am. Chem. Soc. 1996, 118, 4492-4493.
(14) For preparation of allenynes catalyzed by Pd, see: (a) Markl, G.;
Attenberger, P.; Kellner, J. Tetrahedron Lett. 1988, 29, 3651-3654. (b)
Mandai, M.; Nakata, T.; Murayama, H.; Yamaoki, H.; Ogawa, M.; Kawada,
M.; Tsuji, J. Tetrahedron Lett. 1990, 31, 7179-7180. (c) Alami, M.;
Linstrumelle, G. Tetrahedron Lett. 1991, 32, 6109-6112. (d) Condon-
Gueugnot, S.; Linstrumelle, G. Tetrahedron 2000, 56, 1851-1857.
(15) (a) Zimmer, R. Synthesis 1993, 165-178. (b) For reverse Brook
rearrangement, see: Tokeshi, B. K.; Tius, M. A. Synthesis 2004, 5, 786-
790. (c) Sakaguchi, K.; Fujita, M.; Suzuki, H.; Higashino, M.; Ohfune, Y.
Tetrahedron Lett. 2000, 41, 6589-6592.
† Service de Chimie Bioorganique et de Marquage.
‡ Universite´ Louis Pasteur.
§ In memory of Dr. Charles Mioskowski “Miko”, our exceptional supervisor
and friend who died on June 2nd, 2007.
(1) (a) Migliorese, K. G.; Tanaka, Y.; Miller, S. I. J. Org. Chem. 1974,
39, 739-747. (b) Auffant, A.; Diederich, F.; Boudon, C.; Gisselbrecht, J.-
P.; Gross, M. HelV. Chim. Acta 2004, 87, 3085-3105. (c) Convertino, V.;
Manini, P.; Schweizer, W. B.; Diederich, F. Org. Biomol. Chem. 2006, 4,
1206-1208.
(2) Jones, E. R. H.; Lee, H. H.; Whiting, M. C. J. Chem. Soc. 1960,
3483-3489.
(3) Wille, F.; Strasser R. Chem. Ber. 1961, 1606-1611.
(4) (a) Xia, H.; He, G.; Zhang, H.; Wen, T. B.; Sung, H. H. Y.; Williams,
I. D.; Jia, G. J. Am. Chem. Soc. 2004, 126, 6862-6863. (b) Zhang, H.;
Xia, H.; He, G.; Wen, T. B.; Gong, L.; Jia, G. Angew. Chem., Int. Ed.
2006, 45, 2920-2923.
(16) (a) Kuwajima, I.; Kato, M. Tetrahedron Lett. 1980, 21, 623-626.
(b) Kruithof, K. J. H.; Klumpp, G. W. Tetrahedron Lett. 1982, 23, 3101-
3102. (c) Reich, H. J.; Eisenhart, E. K.; Olson, R. E.; Kelly, M. J. J. Am.
Chem. Soc. 1986, 108, 7791-7800.
(5) Maurer, H.; Hopf, H. Eur. J. Org. Chem. 2005, 2702-2707.
10.1021/jo0709753 CCC: $37.00 © 2007 American Chemical Society
Published on Web 06/28/2007
5938
J. Org. Chem. 2007, 72, 5938-5941

SCHEME 1. Synthesis of Bispropargylic Ethers 3a-fa
TABLE 1. Reaction of Alkynes 3d-f, 5d with Bases or TBAF
entry substrate
conditionsa
6d
7d
8d-f
1
2
3
4
5
6
7
8
9
3d
3d
3d
3d
3d
3e
3f
t-BuOK, 0.2 equiv
t-BuOK, 0.5 equiv
t-BuOK, 1 equiv
BuLi, 1 equiv
LDA, 1 equiv, -78 °C 75% 10%
t-BuOK, 1 equiv
t-BuOK, 1 equiv
TBAF, 1 equiv
t-BuOK, 0.5 equiv
49% 18%
b
70% 8d: 20%
8d: 84%
83% 14%
8e: 65%
8f: 59%
8e: 58%
c
3e
5d
a Reaction conditions: (a) PCl, DMAP (3a-d); (b) DHP, PPh3.HBr (3e);
(c) EtMgBr, DMPMBr (3f).
36%
a All of the reactions were run in THF at 0 °C for 5 min (except for
entry 5); see Experimental Section for details. b 3d was recovered (30%
yield). c 5d was recovered (60% yield).
SCHEME 2. Protodesilylation of 3d-f
investigated the reactivity of silylated bispropargylic ether 3d
with different amounts of t-BuOK (entries 1-3). When 3d was
submitted to t-BuOK (0.2 equiv, entry 1) for 5 min, two
differently substituted propargylic allenes 6d (49% yield) and
7d (18% yield) were identified. Use of 0.5 equiv of t-BuOK
under identical conditions afforded 7d (70% yield) and totally
deprotected allenyne ether 8d (20% yield) (entry 2). As
expected, the treatment of 3d with 1 equiv of t-BuOK yielded
allenyne ether 8d as a single product (84%, entry 3). These
results led us to suppose that t-BuOK should promote the
isomerization21 of bispropargylic ether 3d into allenyne ether
6d, which after subsequent TMS cleavages should generate
allenes 7d and/or 8d.
SCHEME 3. Reaction of 3d-f with Bases or TBAF
The reaction of 3d was examined with BuLi22 or LDA (entries
4 and 5): interestingly, allene 6d was obtained in 83 and 75%
yield, respectively, and 7d in 14 and 10% yield, respectively.
Next, the reaction was extended to compounds 3e and 3f (entries
6-8). As expected, t-BuOK promoted the isomerization of 3e
and 3f and the TMS removal to afford allenyne ethers 8e and
8f in 65 and 59% yield, respectively (entries 6 and 7). Similarly,
TBAF generated the transformation of 3e into 8e (65%) (entry
8). Finally, the treatment of mono-TMS-protected alkyne 5d18b
with t-BuOK gave allenyne ether 7d (36% yield, entry 9), which
allowed us to conclude that t-BuOK should first induce the
isomerization of the triple bond into the corresponding allene.
These results revealed the ability of silylated bispropargylic
ethers 3 to provide allenyne ethers 6-8.
At this stage, we were interested in the preparation of
substituted allenyne ethers 6. Therefore, the metalation and the
subsequent trapping of bispropargylic ethers 3d-f were exam-
ined. Unexpectedly, the reaction of 3d-f with BuLi followed
by the addition of TMSCl did not afford the corresponding
trisubstituted allene 6, but the R-substituted bispropargylic ether
9a was isolated as a single product (Scheme 4). The reaction
of bispropargylic ethers 3d-f was therefore undertaken with a
variety of electrophiles. The results are summarized in Table 2.
As indicated in entry 1, the reaction of 3d with BuLi (1 equiv)
and TMSCl (1 equiv) yielded R-trimethylsilyl bispropargylic
ether 9a (39%). Similarly, the metalation of 3d followed by
the alkylation with allyliodide gave the corresponding R-allyl-
bispropargylic ether 9b (entry 2, 45% yield).23 The reaction of
3d with BuLi followed by an aqueous workup afforded the
substituted allenyne ether 6d (entry 3, 80% yield). Interestingly,
trapping of the lithiated bispropargylic ether 3d with Me3SnCl
access to R-substituted bispropargylic alcohols which could be
useful partners in acetylene chemistry to afford new polyal-
kynylated species and oligodiacetylenes.17 Herein we report our
results concerning the synthesis and the reactivity of bispro-
pargylic ethers toward bases and electrophiles.
Starting from the easily available 1,5-bis(trimethylsilyl)-
propargylic alcohol 2,6,8 trimethylsilyl ether 3a, triethylsilyl ether
3b, tert-butyldimethylsilyl ether 3c, tert-butyldiphenylsilyl ether
3d, tetrahydropyranyl ether 3e, and 1,3-dimethoxybenzyl ether
3f were prepared following classical procedures (Scheme 1).
When protected propargylic ethers 3a-c were submitted to
the protodesilylation reaction (methanolic K2CO3 or KOH), only
material loss upon treatment or degradation products were
observed. However, the TMS deprotection of 3d, 3e, and 3f
yielded the corresponding bispropargylic ethers 4d (64%), 4e
(70%), and 4f (65%) (Scheme 2). Monoprotected bispropargylic
ethers 5d-f were not obtained under these reaction conditions.18
The cleavage of the TMS protective groups of bispropargylic
ethers 3d-f was investigated with t-BuOK19 and TBAF.20
Surprisingly, the reaction did not afford the corresponding
deprotected bispropargylic ethers 4d-f or 5d-f, but yielded
the allenyne ethers 6d, 7d, and 8d (Scheme 3).
These interesting results encouraged us to explore the
formation of such allenyne ethers with a variety of basic
conditions. The results are reported in Table 1. First, we
(17) Leibrock, B.; Vostrowsky, O.; Hirsch, A. Eur. J. Org. Chem. 2001,
4401-4409.
(18) (a) Whatever conditions used (time, temperature, equivalent of base),
3d-f yielded mostly 4d-f compared to 5d-f. (b) 5d was successfully
prepared from 4d with BuLi/TMSCl (43% yield); see Supporting Informa-
tion for details.
(19) Alayrac, C. Ph.D. Thesis, University of Strasbourg, France, 1993.
(20) TBAF treatment was employed for 3e,f.
(21) Base-catalyzed isomerization of alkynes has precedent in the
literature: Hopf, H. Chem. Ber. 1971, 104, 3087-3095; see also ref 12.
(22) n-BuLi was used for all of the reactions. s-BuLi gave the same results
(products and yields).
(23) Addition of the electrophile prior to addition of BuLi (internal
quench) gave the same alkylation results.
J. Org. Chem, Vol. 72, No. 15, 2007 5939

SCHEME 4. Alkylation of 3d-f
SCHEME 6. Access to r-Substituted Bispropargylic Alcohol
11
3 and 4), whereas other electrophiles (TMSCl, MeI, allyliodide)
generate R-substituted alkynyl ethers 9a-f (Table 2, entries 1,
2, and 5-11).
The observed results can be explained according to the hard/
soft acid/base principle (HSAB):25 the bispropargylic anion B
is characterized as soft, while the allenyl anion A is classified
as hard. The regioselectivities observed with water, Me3SnCl
(hard electrophiles, Table 2, entries 3 and 4), MeI, dimethyl-
sulfate, allyliodide, and dimethoxybenzylbromide (soft electro-
philes, Table 2, entries 2 and 6-9) may be understood in terms
of HSAB theory favoring a “soft-soft” or a “hard-hard”
combination. However, to our surprise, chlorotrimethylsilane,
classified as a hard electrophile, afforded exclusively R-TMS
alkynyl ethers 9a and 9c (Table 2, entries 1, 5, 10, and 11). In
light of this result, we propose that the charge distribution and
the stability of the bispropargylic species B versus the allenic
species A are very important factors and could outweigh the
HSAB theory.26
TABLE 2. Results of the Metalation/Alkylation
entry
substrate
electrophilea
productb
1
2
3
4
5
6
7
8
9
3d
3d
3d
3d
3e
3e
3e
3e
3f
TMSCl
H2CdCHCH2I
H2O
Me3SnCl
TMSCl
H2CdCHCH2I
CH3I
(CH3)2SO4
DMPMBr
TMSCl
9a: 39%
9b: 45%
6d: 80%
6e: 55%
9c: 79%
9d: 81%
9e: 60%
9e: 55%
9f: 40%
9a: 30%
9a: 24%
10
11
6d
8d
TMSCl
Finally, we attempted to generate R-allylbispropargylic
alcohol 11 from R-allylbispropargylic ether 9d. Removal of the
THP group was achieved with PPTS in EtOH to produce alcohol
10 (89% yield), which after protodesilylation with K2CO3
yielded R-allylbispropargylic alcohol 12 (65%) (Scheme 6).
This successful preparation of alcohol 11 from 9d is an
alternative method of the known addition of a metalate species
to corresponding bispropargylic ketones27 and should allow
access to a broad range of substituted alcohols 11 that are useful
in transition-metal-catalyzed cyclizations.
a Reaction conditions: BuLi (1 equiv), electrophile (1 equiv), THF, -78
°C, 10 min. b Isolated yields 3d: P ) TBDPS, 3e: P ) THP, 3f: P )
DMPM, 9a: P ) TBDPS, E ) TMS, 9b: P ) TBDPS, E ) H2CdCH-
CH2I, 9c: P ) THP, E ) TMS, 9d: P ) THP, E ) H2CdCH-CH2I, 9e:
P ) THP, E ) Me, 9f: P ) DMPM, E ) DMPM; 6d: P ) TBDPS, E )
TMS, 6e: P ) TBDPS, E ) SnMe3.
SCHEME 5. Formation of 6d, 6e, and 9a-f
In conclusion, we have reported the reaction of 1,5-bis-
(trimethylsilyl)propargylic ethers 3 toward bases (t-BuOK, LDA,
BuLi) and TBAF, generating allenyne ethers 6-8 in good yields.
Interestingly, the lithiation of 3 followed by the trapping with
Me3SnCl afforded stannylated allene 6e. These substituted
allenes represent versatile and useful building blocks in organic
synthesis since they can be transformed into olefins, R,â-
unsaturated carbonyl compounds, and propargylation products.
Moreover, we have developed an access to R-substituted
bispropargylic alcohols 9a-f by lithiation of the bisacetylenic
synthon 3 followed by the subsequent addition of an electrophile.
This methodology is an alternative method to the reported
addition of a metalate species to a functionalized bispropargylic
ketone. Finally, this study confirms the ambident behavior of
metalated synthon 3 yielding either acetylenic compounds or
allenic compounds. Further studies concerning the application
of our methodology in organic synthesis are ongoing in our
laboratory.
yielded the stannylated allenyne ether 6e (entry 4, 55%). Then
the reaction was extended to substrates 3e and 3f and to various
electrophiles (entries 5-9). The reaction of the lithiated bispro-
pargylic ether 3e with TMSCl, allyliodide, methyliodide, or
dimethylsulfate yielded the corresponding R-substituted alkynyl
ethers 9c-e in good yields (55-81%). The alkylation of 3f with
BuLi and 1,3-dimethoxybenzylbromide afforded 9f (40% yield).
Furthermore, alkylations were directly carried out on allenes
6d and 8d (entries 10 and 11): metalation of allenes 6d and 8d
with BuLi, followed by trapping with TMSCl, produced
R-trimethylsilyl bispropargylic ether 9a as a single product in
30 and 24% yield, respectively.24 All of our attempts to extend
this reaction to aldehydes and ketones gave complex mixtures
where allenes or acetylenic products were not identified.
The results reported in Table 2 suggested that the regio-
selectivity of the alkylation is depending on the nature of the
electrophile. Presumably, the reaction of 3d-f with BuLi is
occurring via a mesomeric ambident carbanion able to react
either under its allenyllithiated form A or under its bispropar-
gyllithiated form B (Scheme 5). Addition of water or Me3SnCl
provides allenyne ether 6d and 6e, respectively (Table 2, entries
(24) These low yields are due to the instabilities of 6d and 8d.
(25) (a) Pearson, R. G.; Songstad, J. J. Am. Chem. Soc. 1967, 89, 1827-
1836. (b) Ho, T.-S. Chem. ReV. 1975, 75, 1-20.
(26) HSAB rationalization and inconsistent reactivity were previously
reported for lithiated allenes: (a) Creary, X. J. Am. Chem. Soc. 1977, 99,
7632-7639. (b) Leroux, Y.; Roman, C. Tetrahedron Lett. 1973, 28, 2585-
2586. (c) Grovenstein, E., Jr.; Chiu, K.-W.; Patil, B. B. J. Am. Chem. Soc.
1980, 102, 5848-5859. (d) Langer, P.; Do¨ring M.; Seyferth, D.; Go¨rls, H.
Chem.sEur. J. 2001, 7, 573-584.
(27) Livingston, R.; Cox, L. R.; Odermatt, S.; Diederich, F. HelV. Chim.
Acta 2002, 85, 3052-3077.
5940 J. Org. Chem., Vol. 72, No. 15, 2007

extracted with Et2O. The organic layer was separated, washed with
H2O and brine, dried over magnesium sulfate, and concentrated
under vacuum to yield 40 mg of a mixture of 7d (70%) and 8d
(20%) unseparable by flash chromatography. 7d: 1H NMR (CDCl3)
δ 7.74-7.71 (m, 4H), 7.44-7.36 (m, 6H), 5.02 (s, 2H), 1.09 (s,
9H), 0.12 (s, 9H); 13C NMR (CDCl3) δ 209.5, 135.7, 133.1, 129.6,
127.4, 112.6, 100.8, 97.8, 87.7, 26.5, 19.2, -0.13.
Experimental Section
(3-(tert-Butyldiphenylsilanyloxy)penta-1,4-diyne-1,5-diyl)bis-
trimethylsilane (3d). To a stirred solution of bistrimethylsilyl
propargylic alcohol 26,8 (100 mg, 0.44 mmol) in CH2Cl2 (7 mL)
were added tert-butyldiphenylsilyl chloride (0.12 mL, 0.48 mmol)
and DMAP (0.48 mmol), and the reaction was stirred at room
temperature for 3 h. The mixture was concentrated, diluted with
Et2O (15 mL), and washed with brine (10 mL). The organic layer
was separated, dried over anhydrous MgSO4, and concentrated
under vacuum. The crude product was purified by flash chroma-
tography on silica gel (pentane/Et2O: 98/2) to afford 3d (177 mg,
90%) as a white solid: 1H NMR (CDCl3) δ 7.78 (d, J ) 7.1 Hz,
4H), 7.46-7.40 (m, 6H), 5.11 (s, 1H), 1.11 (s, 9H), 0.18 (s, 18H);
13C NMR (CDCl3) δ 135.8, 132.8, 129.7, 127.5, 102.2, 88.9, 54.7,
26.6, 19.2, -0.5; IR (neat, cm-1) 2959, 2181, 1592, 1062, 848;
mp 71 °C; MS (TOF) m/z (M + Na+) ) 485; HRMS calcd for
C27H38OSi3Na [M + Na+] ) 485.2128, found ) 485.2111.
tert-Butyl-(1-ethynylprop-2-ynyloxy)diphenylsilane (4d). To
a stirred solution of bispropargylic ether 3d (115 mg, 0.25 mmol)
in MeOH (6 mL) was added K2CO3 (35 mg, 0.25 mmol). The
reaction mixture was stirred at room temperature for 1 h and then
was quenched with saturated ammonium chloride (10 mL) and
extracted with Et2O (3 × 10 mL). The organic layer was separated,
washed with H2O and brine, dried over anhydrous MgSO4, filtered,
and concentrated under vacuum. The crude residue was purified
by silica gel flash chromatography (pentane/CH2Cl2: 98/2) to afford
4d (48 mg, 60%) as a colorless oil: 1H NMR (CDCl3) δ 7.76 (d,
J ) 6.5 Hz, 4H), 7.48-7.39 (m, 6H), 5.08 (t, J ) 2.2 Hz, 1H),
2.49 (d, J ) 2.2 Hz, 2H), 1.11 (s, 9H); 13C NMR (CDCl3) δ 135.8,
tert-Butyl-(1-ethynylpropa-1,2-dienyloxy)diphenylsilane (8d).
To a stirred solution of bistrimethylsilyl propargylic ether 3d (200
mg, 0.44 mmol) in THF (6 mL) was added t-BuOK (53.8 mg, 0.44
mmol). The resulting brown reaction was stirred at room temper-
ature for 10 min. The solution was quenched with saturated
ammonium chloride and extracted with Et2O. The organic layer
was separated, washed with H2O and brine, dried over magnesium
sulfate, and concentrated under vacuum. The crude was purified
by flash chromatography (pentane/CH2Cl2: 98/2) to afford 8d as
an unstable yellow oil (117 mg, 84%): 1H NMR (CDCl3) δ 7.74-
7.71 (m, 4H), 7.45-7.37 (m, 6H), 4.92 (d, J ) 1.6 Hz, 2H), 3.27
(s, 1H), 1.08 (s, 9H); 13C NMR (CDCl3) δ 209.1, 135.6, 132.5,
129.7, 127.4, 111.9, 88.3, 82.3, 77.5, 26.5, 19.2; IR (neat, cm-1
3308, 2930, 1944, 1109, 701.
)
3-(tert-Butyldiphenylsilanyloxy)-1,3,5-tristrimethylsilanyl-
penta-1,4-diyne (9a). To a stirred solution of 3d (100 mg, 0.22
mmol) in THF (5 mL) at -78 °C were added dropwise n-BuLi
(0.22 mL, 1.6 M in hexane, 0.22 mmol) and then a solution of
TMSCl (26 µL, 0.22 mmol) in THF (1 mL). After stirring for 10
min at -78 °C, the reaction was quenched with saturated am-
monium chloride, warmed to rt, and extracted with Et2O. The
organic layer was separated, washed with H2O and brine, dried
over magnesium sulfate, and concentrated under vacuum. Purifica-
tion by flash chromatography (pentane) afforded 9a (46 mg, 39%)
as a colorless oil: 1H NMR (CDCl3) δ 7.75 (d, J ) 6.8 Hz, 4H),
7.40-7.30 (m, 6H), 1.09 (s, 9H), 0.26 (s, 9H), 0.01 (s, 18H); 13C
NMR (CDCl3) δ 136.7, 134.5, 129.1, 126.8, 103.9, 92.8, 61.2, 27.0,
19.3, -0.4, -4.5; IR (neat, cm-1) 2959, 2180, 1590, 1062, 845;
MS (TOF) m/z (M + Na+) ) 557.
1-Trimethylsilanyl-3-trimethylsilanylethynylhex-5-en-1-yn-3-
ol (10). To a stirred solution of 9d (177 mg, 0.51 mmol) in EtOH
(20 mL) was added PPTS (65 mg, 026 mmol). The reaction was
stirred at 60 °C until completion (for about 2.5 h) and was quenched
with H2O and diluted with Et2O. The organic layer was separated,
washed with H2O and brine, dried over magnesium sulfate, and
concentrated under vacuum. The crude was purified by flash
chromatography (pentane/Et2O: 9/1) to afford 10 as a yellow oil
(120 mg, 89%): 1H NMR (CDCl3) δ 5.99-5.92 (m, 1H), 5.26-
5.21 (m, 2H), 2.67 (d, J ) 7.2 Hz, 2H), 0.19 (s, 18H); 13C NMR
(CDCl3) δ 131.7, 119.9, 104.4, 88.5, 63.0, 48.2, -0.4; IR (neat,
cm-1) 3447, 2961, 2175, 1251, 844, 760; MS (TOF) m/z (M +
Na+) ) 287.
3-Ethynylhex-5-en-1-yn-3-ol (11). To a stirred solution of 10
(120 mg, 0.45 mmol) in MeOH (10 mL) was added K2CO3 (62
mg, 0.45 mmol). The reaction was stirred at room temperature for
1 h and was quenched with saturated ammonium chloride and
diluted with Et2O. The organic layer was separated, washed with
H2O and brine, dried over magnesium sulfate, and concentrated
under vacuum. The crude was purified by flash chromatography
(pentane/Et2O: 8/2) to afford 11 as a colorless oil (35 mg, 65%):
1H NMR (CDCl3) δ 6.03-5.93 (m, 1H), 5.29-5.25 (m, 2H), 2.71
(d, J ) 7.2 Hz, 2H), 2.60 (s, 2H); 13C NMR (CDCl3) δ 131.2,
120.5, 83.1, 72.3, 62.2, 47.7; IR (neat, cm-1) 3308, 2927, 2376,
1249, 840.
132.4, 130.0, 127.7, 80.9, 72.4, 53.5, 26.6, 19.2; IR (neat, cm-1
)
3292, 2126, 1428, 1111, 703; MS (TOF) m/z (M + K+) ) 357.
3-(tert-Butyldiphenylsilanyloxy)-1,5-bistrimethylsilanylpenta-
1,2-dien-4-yne (6d). To a stirred solution of 3d (100 mg, 0.22
mmol) in THF (5 mL) at rt was added dropwise n-BuLi (0.22 mL,
1.6 M in hexane, 0.22 mmol). After 5 min of stirring, the reaction
was quenched with saturated ammonium chloride and extracted with
Et2O. The organic layer was separated, washed with H2O and brine,
dried over magnesium sulfate, and concentrated under vacuum.
Purification of the crude by flash chromatography with pentane
afforded 6d as a brown oil (84 mg, 80%): 1H NMR (CDCl3) δ
7.75-7.73 (m, 4H), 7.42-7.37 (m, 6H), 5.48 (s, 1H), 1.09 (s, 9H),
0.11 (s, 9H), -0.06 (s, 9H); 13C NMR (CDCl3) δ 212.3, 135.8,
132.8, 129.7, 127.5, 110.2, 101.7, 100.3, 98.9, 26.6, 19.2, -0.4,
-1.5; IR (neat, cm-1) 2957, 2148, 1922, 1472, 1313, 1112, 838,
698; MS (TOF) m/z (M + Na+) ) 881; HRMS calcd for C57H74-
OSi3 ) 858.5047, found ) 858.5060.
3-(tert-Butyldiphenylsilanyloxy)-1-(trimethylstannyl)-1,5-bist-
rimethylsilanylpenta-1,2-dien-4-yne (6e). To a stirred solution of
3d (100 mg, 0.22 mmol) in THF (5 mL) at -78 °C was added
dropwise n-BuLi (0.22 mL, 1.6 M in hexane, 0.22 mmol). A
solution of trimethyltin chloride (44 mg, 0.22 mmol) in THF (0.25
mL) was then added. After stirring for 30 min at -78 °C, the
reaction was quenched with saturated ammonium chloride, warmed
to rt, and extracted with Et2O. The organic layer was separated,
washed with H2O and brine, dried over magnesium sulfate, and
concentrated under vacuum. The crude was purified by Kugelrohr
distillation to afford 6e (76 mg, 55%) as a yellow oil: 1H NMR
(CDCl3) δ 7.78-7.76 (m, 4H), 7.40-7.35 (m, 6H), 1.03 (s, 9H),
0.11 (s, 9H), 0.10 (s, 9H), -0.06 (s, 9H); 13C NMR (CDCl3) δ
209.1, 135.8, 133.4, 129.4, 127.4, 107.6, 106.5, 104.2, 101.5, 26.5,
19.3, -0.4, -7.5; IR (neat, cm-1) 2959, 2151, 1956, 1589, 1250,
1112, 845; HRMS calcd for C30H46OSi3Sn ) 626.1878, found )
626.1880.
Supporting Information Available: General information,
experimental procedures, and characterization data for compounds
3a-c, 3e,f, 4e,f, 5d, 8e,f, and 9b-f, and copies of 1H and 13C NMR
spectra for all compounds. This material is available free of charge
via the Internet at http://pubs.acs.org.
3-(tert-Butyldiphenylsilanyloxy)-5-trimethylsilanylpenta-1,2-
dien-4-yne (7d). To a stirred solution of ether 3d (50 mg, 0.11
mmol) in THF (3 mL) was added t-BuOK (7 mg, 0.06 mmol). The
resulting brown mixture was stirred at room temperature for 2 min
and was then quenched with saturated ammonium chloride and
JO0709753
J. Org. Chem, Vol. 72, No. 15, 2007 5941