Synthesis of highly functionalized propargylic alcohols: Direct addition of epoxy acetylides to aldehydes and ketones

Article abstract of DOI:10.1002/1522-2675(200210)85:10<3176::AID-HLCA3176>3.0.CO;2-7

Direct nucleophilic addition of terminal alkynes comprising an epoxy group to aldehydes and ketones is reported with BuLi or lithium diisopropylamide for the generation of the corresponding lithium acetylides. This alkynylation reaction tolerates a wide variety of different functional groups (e.g., alcohols, silyl ethers, halides, double bonds) in the carbonyl compound, as well as in the acetylenic nucleophile, and furnishes highly functionalized propargylic alcohols in good-to-excellent yields. The method is particularly useful for the regioselective introduction of an epoxide function into multiply unsaturated target molecules.

Full text of DOI:10.1002/1522-2675(200210)85:10<3176::AID-HLCA3176>3.0.CO;2-7

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Helvetica Chimica Acta Vol. 85 (2002)
Synthesis of Highly Functionalized Propargylic Alcohols: Direct Addition of
Epoxy Acetylides to Aldehydes and Ketones
by Anja Hoffmann-Rˆder and Norbert Krause*
Organic Chemistry II, Dortmund University, D-44221 Dortmund
(e-mail: norbert.krause@uni-dortmund.de)
Dedicated to Professor Dieter Seebach on the occasion of his 65th birthday
Direct nucleophilic addition of terminal alkynes comprising an epoxy group to aldehydes and ketones is
reported with BuLi or lithium diisopropylamide for the generation of the corresponding lithium acetylides. This
alkynylation reaction tolerates a wide variety of different functional groups (e.g., alcohols, silyl ethers, halides,
double bonds) in the carbonyl compound, as well as in the acetylenic nucleophile, and furnishes highly
functionalized propargylic alcohols in good-to-excellent yields. The method is particularly useful for the
regioselective introduction of an epoxide function into multiply unsaturated target molecules.
Introduction. The addition of C nucleophiles to aldehydes and ketones belongs to
the most important C,C-bond-forming processes in organic synthesis [1]. In this
respect, acetylides represent a particularly versatile class of C nucleophiles, since the
resulting propargylic alcohols are prone to undergo further transformations and, thus,
constitute important building blocks for an abundance of natural products (for some
selected examples, see [2]), pharmacologically active compounds (for some selected
examples, see [3]), and structurally interesting molecules [4]. Consequently, several
synthetic strategies for the incorporation of acetylenic entities into carbonyl
compounds have been established [5].
Complex molecules, e.g., natural products, often require in their synthesis the
assembly of highly functionalized precursors, resulting from multistep transformations.
Thus, from an economic point of view, the development of convergent synthetic
strategies, which allow an early introduction of all necessary functionalities into the
molecule, is highly rewarding. In the course of our workon the synthesis of 2,5-
dihydrofurans from propargylic oxiranes via a-hydroxyallenes [6], we became
interested in the synthesis of propargylic alcohols comprising an epoxide moiety
through direct addition of an epoxy acetylide to an aldehyde or ketone. This reaction
would be particularly useful for the regioselective introduction of an oxirane ring into
multiply unsaturated target molecules where a direct alkene epoxidation is expected to
furnish a mixture of regioisomers.
To the best of our knowledge, there is only scattered precedence for the formation
of metal acetylides bearing an epoxide ring [7], and only one example for the direct
deprotonation of an epoxy alkyne and the subsequent addition to a carbonyl compound
[8]. This is not surprising, since nucleophiles containing an electrophilic moiety are
involved, and for a successful transformation of this kind, two requirements have to be
met: i) the base used for the deprotonation of the epoxy alkyne should not undergo

Helvetica Chimica Acta Vol. 85 (2002)
3177
direct nucleophilic attackat the oxirane ring, and ii) the acetylide formed should react
with the carbonyl group and not with another epoxide. In this account, we report our
findings on the formation and addition of epoxy acetylides to aldehydes and ketones, as
well as the application to the synthesis of versatile multifunctionalized propargylic
building blocks in only one step.
Results and Discussion.
First, the addition of epoxy acetylides to carbonyl
compounds was investigated with oxirane 1a, which is easily accessible from (Z)-pent-
2-en-4-yn-1-ol [9], and cyclohexanone (2a) as test substrates (Scheme 1). To avoid
nucleophilic attackat the epoxide ring, non-nucleophilic bases like lithium diisopro-
pylamide (LDA), lithium hexamethyldisilazide (LHMDS), and its potassium counter-
part (KHMDS) were used for the acetylide formation in THF, giving the addition
product 3a in 86, 76, and 72% yield, respectively. Strikingly, even the use of the more
nucleophilic BuLi as a base resulted in the clean formation of product 3a, which was
obtained in 86% yield in THF as solvent (83% in Et2O). No side products formed by
the undesired reactions mentioned above or by enolization of the ketone were
observed.
Scheme 1
O
O
1. Base
2.
HO
O
OTBS
OTBS
1a
2a
3a
By contrast, transmetallation of the Li-acetylide of 1a with (i-PrO)3TiCl to the
corresponding Ti-acetylide [10] furnished only small amounts of the desired addition
product. Here, as in the case of Carreira×s protocol (with Zn(OTf)2/N-methylephe-
drine) [5d], complex reaction products were obtained, probably because of the Lewis
acidity of (i-PrO)3TiCl and Zn(OTf)2, respectively. Moreover, application of Knochel×s
method (with CsOH ¥ H2O) [5b] furnished, as a result of its low reactivity, only 26% of
the desired propargylic alcohol 3a.
Subsequently, we investigated the scope and limitations of the alkynylation reaction
with BuLi as a base. Thus, a variety of different aldehydes and ketones, which cover
saturated, unsaturated, and aromatic representatives, were reacted with alkyne 1a and
the corresponding free alcohol 1b (Scheme 2 and Table).
Scheme 2
O
O
1. BuLi
R1
R2 OH
R1
2.
O
OR
OR
R2
1a (R = TBS)
1b (R = H)
2
3

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Helvetica Chimica Acta Vol. 85 (2002)
Table. Nucleophilic Addition of Epoxy Alkynes 1 to Carbonyl Compounds 2
Entry
Alkyne
Carbonyl compound
R1
Product (yield [%])
R2
1
2
3
4
5
6
7
8
9
1a
1b
1a
1a
1a
1b
1b
1a
1a
1a
À(CH2)5À
À(CH2)5À
ÀMe2C(CH2)4À
ÀCHˆCH(CH2)3À
Me
cyclopropyl
C5H11CHˆCH
Ph
3a (86)
3b (91)
3c (75)
3d (78)
3e (94)
3f (31)
3g (65)
3h (57)
3i (28)
3j (83)
Me
Me
H
H
Me
H
Ph
4-BrC6H4
10
As can be seen from the Table, both aldehydes and ketones can be transformed
smoothly into the corresponding propargylic derivatives 3 in good-to-excellent yields.
In particular, cyclohexanone derivatives proved to be profitable substrates even in the
presence of an adjacent quaternary center (Entry 3). By contrast, the addition of 1a/1b
to acyclic ketones gave mixed results: whereas the reaction with acetone proceeded
uneventfully to give the expected adduct 3e in 94% yield (Entry 5), the analogous
reaction with cyclopropyl methyl ketone was not satisfactory, most probably due to the
high ring strain. As a consequence, a complex product mixture was obtained with only
31% yield of the cyclopropyl-substituted propargylic alcohol 3f (Entry 6).
Nonetheless, the addition of epoxy-substituted alkynes to aldehydes and ketones, as
outlined above, appears to be a generally applicable method. Hence, this reaction
tolerates besides simple alkyl-substituted electrophiles even those comprising further
functionalities in the molecule, e.g., CˆC bonds (even in conjugation to the CˆO
group), aromatic substituents, and halides. In this respect, the resulting propargylic
derivatives containing a reactive CˆC bond (Entries 4 and 7) are particularly
interesting, since they are not accessible via the conventional additionÀepoxidation
sequence (see below). In both cases, the addition takes place regioselectively to furnish
the 1,2-addition products only. In the case of the less reactive PhCHO (Entry 8) and
acetophenone (Entry 9), however, the reaction proceeded sluggishly, furnishing the
desired addition products in only moderate yields (in the case of acetophenone,
enolization may also contribute to the low yield). Here, as expected, introduction of an
electron-withdrawing group in para-position activated the substrate and improved the
yield (Entry 10), notably without any halogen/metal exchange. A particularly
interesting example is the reaction of the lithium acetylide formed from 1a and BuLi
with the ambident electrophile 2,3-epoxycyclohexanone (2k); again, the addition takes
place regioselectively to give the product 3k comprising two different epoxide moieties
(77% yield; Scheme 3).
Even cyclic epoxides containing a terminal triple bond, e.g., 4 [11], can be applied in
the addition to cyclohexanone (2a; Scheme 4). As before, the reaction proceeded
smoothly leading to propargylic alcohol 5 as the sole product in 81% yield. The
corresponding addition to acetaldehyde (6a) and 1,1,1-trifluoroacetone (6b) gave also
the desired alcohols 7a/b with reasonable 61 and 57% yield, respectively.

Helvetica Chimica Acta Vol. 85 (2002)
3179
Scheme 3
O
O
HO
O
1. BuLi
2.
O
OTBS
OTBS
1a
O
2k
3k (77%)
Scheme 4
O
OH
2a
O
5 (81%)
BuLi
O
OH
H3C
O
R
4
R
6
O
7a R = H (61%)
7b R = CF3 (57%)
Finally, to demonstrate the applicability of the method to the assembly of complex,
multiply unsaturated target molecules, the epoxy acetylide formed from 1a and BuLi
was added to vitamin A building blocks. Reaction with the sterically hindered aldehyde
b-cyclocitral (8) gave the addition product 9 in 68% yield, whereas the corresponding
addition to the b-C14-aldehyde 10 [12] furnished the expected adduct 11 with an
exceptionally high 97% yield (Scheme 5). The latter is an intermediate in the projected
synthesis of a vitamin A metabolite comprising a 2,5-dihydrofuran unit [13]. As
expected, epoxypropargylic alcohol 11 cannot be directly obtained by epoxidation of
the trienyne 12 (prepared in analogy to the corresponding diol [14]); treatment of the
latter with m-chloroperbenzoic acid (mCPBA) provided a complex mixture of several
oxiranes and other by-products.
Conclusions. We reported the direct addition of lithium acetylides bearing an
epoxy group to aldehydes and ketones. This alkynylation reaction not only leads to the
generation of the corresponding functionalized propargylic alcohols in good-to-
excellent yields, but is also compatible with a variety of different functional groups (e.g.,
alcohols, silyl ethers, halides, CˆC bonds) in both reaction partners. Moreover, the
reaction can be conducted in a very simple manner with LDA or BuLi as a base. The
method is particularly useful for the regioselective introduction of an epoxide
functionality into multiply unsaturated target molecules.

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Helvetica Chimica Acta Vol. 85 (2002)
Scheme 5
CHO
OH
OTBS
8
O
O
9 (68%)
BuLi
CHO
OTBS
O
1a
10
OTBS
OH
11 (97%)
mCPBA
Na2HPO4
OTBS
OH
12
Experimental Part
General. The reactions were carried out in thoroughly dried glassware under Ar. Et2O and THF were
distilled from Na/benzophenone prior to use. BuLi was titrated with diphenylacetic acid according to the
procedure of Kofron and Baclawski [15]. GC Analyses were carried out with a Carlo-Erba GC-8000 gas
chromatograph with He as carrier gas and an OV-1701 cap. column. IR Spectra: Bruker IFS66 FT-IR
spectrometer. FAB-MS: Jeol SX102A spectrometer. NMR Spectra: Bruker DRX-400 or DRX-500 spectrom-
eter, in CDCl3 or C6D6 as solvent and internal standard; abbreviations for 13C-NMR DEPT spectra: ‡ : CH3,
CH, À : CH2, x: C(quart.).
General Procedure for the Addition of Epoxy Acetylides to Aldehydes and Ketones. To a soln. of the epoxy
acetylene 1 or 4 (2.2 mmol) in ca. 25 ml of dry THF (or Et2O) under Ar, 2.2 mmol (4.4 mmol in the case of 1b) of
BuLi were added at À808. The resulting soln. was stirred for 15 min at this temp., and 2.2 mmol of the carbonyl
compound, dissolved in ca. 5 ml of THF (or Et2O), were added. The mixture was allowed to warm to r.t. and was
stirred for additional 30 min. After hydrolysis with 15 ml of a sat. NH4Cl soln., the aq. phase was washed with
Et2O (3 Â 10 ml). The combined org. layers were washed with brine, dried, and the solvent was evaporated in
vacuo. Flash column chromatography (FC) (SiO2; cyclohexane/AcOEt 10 :1) afforded the propargylic alcohol.
1-[2-(cis-3-{[(tert-Butyl)dimethylsilyloxy]methyl}-2-methyloxiran-2-yl)ethynyl]cyclohexan-1-ol (3a). From
500 mg (2.2 mmol) of 1a in 25 ml of THF, 1.4 ml (2.2 mmol) of BuLi (1.6m in hexane) and 217 mg (2.2 mmol) of
cyclohexanone in 5 ml of THF; yield: 620 mg (86%) of 3a. Slightly yellow liquid. IR (neat): 3415s, 2933s, 2858s.
1H-NMR (500 MHz, C6D6): 4.01 (dd, 2J(H,H) ˆ 11.5, 3J(H,H) ˆ 5.0, 1 H, CH2O); 3.94 (dd, 2J(H,H) ˆ 11.5,
3J(H,H) ˆ 5.5, 1 H, CH2O); 2.96 (yt, CHÀO); 1.93 (s, OH); 1.88 1.77 (m, CH2); 1.56 1.49 (m, 3 CH2); 1.41
1.27 (m, 1 H, CH2); 1.35 (s, MeCO); 1.11 1.00 (m, 1 H, CH2); 0.99 (s, t-Bu); 0.14, 0.12 (2s, Me2Si). 13C-NMR
(125 MHz, C6D6): 89.0 (x, C(1')); 81.7 (x, C(2')); 68.2 (x, C(1)); 64.4 (‡, C(3'')); 63.8 (À, CH2O); 51.7 (x, C(2''));
40.1 (À, C(2), C(6)); 26.1 (‡, Me3C); 25.4, 23.5 (2 À , C(3), C(4), C(5)); 23.4 (‡, MeÀC(2'')); 18.5 (x, Me3C),
‡
‡
À5.0, À5.2 (2 ‡ , Me2Si). FAB-MS: 347 (8, [M ‡ Na] ), 323 (14, [M À H] ), 277 (60), 249 (48), 163 (95), 133
‡
(88), 73 (100). HR-FAB-MS: calc. for C18H32O3Si (324.53): 347.2018 ([M ‡ Na] ); found: 347.2025.
1-{2-[cis-3-(Hydroxymethyl)-2-methyloxiran-2-yl]ethynyl}cyclohexan-1-ol (3b). From 500 mg (4.5 mmol)
of 1b in 30 ml of THF, 5.9 ml (8.9 mmol) of BuLi (1.5m in hexane), and 438 mg (4.5 mmol) of cyclohexanone in
5 ml of THF; yield: 855 mg (91%) of 3b. Slightly yellow oil. IR (neat): 3420s, 2933s, 2861s. 1H-NMR (500 MHz,
C6D6): 4.33 (s, OH); 4.18 (s, OH); 3.97 (m, CH2O); 3.05 (t, 3J(H,H) ˆ 5.5, HÀC(3'')); 2.02 1.93 (m, CH2);
1.71 1.58 (m, 2 CH2); 1.55 1.47 (m, CH2); 1.40 (s, Me); 1.39 1.34 (m, 1 H, CH2); 1.25 1.17 (m, 1 H, CH2).

Helvetica Chimica Acta Vol. 85 (2002)
3181
13C-NMR (125 MHz, C6D6): 89.2 (x, C(1')); 81.5 (x, C(2')); 68.4 (x, C(1)); 64.3 (‡, C(3'')); 62.5 (À, CH2O); 52.2
(x, C(2'')); 40.0 (À, C(2), C(6)); 25.5, 23.5 (2 À , C(3), C(4), C(5)); 23.4 (‡, Me). FAB-MS: 193 (20, [M À
‡
OH] ), 73 (100).
1-[2-(cis-3-{[(tert-Butyl)dimethylsilyloxy]methyl}-2-methyloxiran-2-yl)ethynyl]-2,2-dimethylcyclohexan-1-
ol (3c). From 500 mg (2.2 mmol) of 1a in 25 ml of THF, 1.5 ml (2.2 mmol) of BuLi (1.5m in hexane), and 279 mg
(2.2 mmol) of 2,2-dimethylcyclohexanone in 5 ml of THF; yield: 585 mg (75%) of 3c. Slightly yellow liquid. IR
(neat): 3471m, 2931s, 2859s. 1H-NMR (500 MHz, CDCl3): 3.91 (dd, 2J(H,H) ˆ 11.5, 3J(H,H) ˆ 4.5, 1 H, CH2O);
3.75 (dd, 2J(H,H) ˆ 11.5, 3J(H,H) ˆ 5.7, 1 H, CH2O); 3.01 (yt, HÀC(3'')); 1.92 (s, OH); 1.76 1.73 (m, CH2);
1.63 1.61 (m, 1 H, CH2); 1.53 (s, MeÀC(2'')); 1.43 1.36 (m, 2 CH2); 1.05 (s, MeÀC(2)); 0.98 (s, MeÀC(2));
0.89 (s, t-Bu); 0.07, 0.07 (2s, Me2Si). 13C-NMR (125 MHz, CDCl3): 87.8 (x, C(1')); 82.1 (x, C(2')); 73.8 (x, C(1));
64.6, 64.5 (2 ‡ , C(3'')); 63.4 (À, CH2O); 51.6 (x, C(2'')); 37.9, 37.9 (2x, C(2)); 36.2 (À, C(3)); 35.6, 35.5 (2 À ,
C(6)); 25.8 (‡, Me3C); 25.4 (‡, MeÀC(3)); 23.4 (‡, MeÀC(2'')); 22.6, 21.0 (2 À , C(4), C(5)); 18.3 (x, Me3C);
‡
‡
À5.2, À 5.3 (2 ‡ , Me2Si). FAB-MS: 375 (19, [M ‡ Na] ), 351 (16, [M À H] ), 295 (45), 277 (32), 203 (46), 191
‡
(95), 161 (63), 105 (36), 73 (100). HR-FAB-MS: calc. for C20H36O3Si (352.59): 375.2331 ([M ‡ Na] ); found:
375.2360.
1-[2-(cis-3-{[(tert-Butyl)dimethylsilyloxy]methyl}-2-methyloxiran-2-yl)ethynyl]cyclohex-2-en-1-ol (3d).
From 500 mg (2.2 mmol) of 1a in 25 ml of Et2O, 1.5 ml (2.2 mmol) of BuLi (1.5m in hexane), and 212 mg
(2.2 mmol) of cyclohex-2-enone in 5 ml of Et2O; yield: 556 mg (78%) of 3d. Slightly yellow liquid. IR (neat):
1
3424m, 3030w, 2931s, 2858s, 1649m. H-NMR (400 MHz, CDCl3): 5.80 (dt, 3J(H,H) ˆ 10.0, 3.5, HÀC(3)); 5.68
(d, 3J(H,H) ˆ 10.0, HÀC(2)); 3.86, 3.86 (2dd, 2J(H,H) ˆ 11.8, 3J(H,H) ˆ 5.0, 1 H), 3.75 (dd, 2J(H,H) ˆ 11.8,
3J(H,H) ˆ 5.3, 1 H, CH2O); 3.01, 3.01 (2yt, HÀC(3'')); 2.23 (s, OH); 2.00 1.94 (m, 3 H, CH2(4), CH2(5),
CH2(6)); 1.90 1.83 (m, 1 H, CH2(4), CH2(5), CH2(6)); 1.75 1.72 (m, 2 H, CH2(4), CH2(5), CH2(6)); 1.53
(s, MeÀC(2'')); 0.89 (s, t-Bu); 0.08, 0.07 (2s, Me2Si). 13C-NMR (100 MHz, CDCl3): 130.0, 130.0, 129.9, 129.9 (4 ‡
, C(2), C(3)); 88.0 (x, C(1')); 80.7 (x, C(2')); 65.1 (x, C(1)); 64.5, 64.4 (2 ‡ , C(3'')); 63.0, 63.0 (2 À , CH2O); 51.8
(x, C(2'')); 37.7, 37.6 (2 À , C(6)); 25.8 (‡, Me3C); 24.5, 19.0, 19.0 (3 À , C(4), C(5)); 23.2 (‡, MeÀC(2'')); 18.3 (x,
‡
Me3C), À5.2, À5.3 (2 ‡ , Me2Si). FAB-MS: 321 (4, [M À H] ), 305 (45), 277 (15), 247 (10), 173 (12), 161 (30),
‡
131 (63), 73 (100). HR-FAB-MS: calc. for C18H30O3Si (322.52): 321.1882 ([M À H] ); found: 321.1878.
4-(cis-3-{[(tert-Butyl)dimethylsilyloxy]methyl}-2-methyloxiran-2-yl)-2-methylbut-3-yn-2-ol (3e). From
2.00 g (8.8 mmol) of 1a in 50 ml of THF, 3.9 ml (8.8 mmol) of BuLi (2.3m in hexane), and 513 mg (8.8 mmol)
of acetone; yield: 2.36 g (94%) of 3e. Slightly yellow liquid. IR (neat): 3403m, 2931s, 2858s. 1H-NMR (500 MHz,
CDCl3): 3.85 (dd, 2J(H,H) ˆ 11.7, 3J(H,H) ˆ 5.2, 1 H, CH2); 3.76 (dd, 2J(H,H) ˆ 11.7, 3J(H,H) ˆ 5.2, 1 H, CH2);
3.00 (t, 3J(H,H) ˆ 5.2, HÀC(3')); 2.18 (s, OH); 1.52 (s, MeÀC(2')); 1.48 (s, MeÀC(2)); 0.89 (s, t-Bu); 0.08, 0.08
(2s, Me2Si). 13C-NMR (125 MHz, CDCl3): 89.3 (x, C(3)); 79.2 (x, C(4)); 65.0 (x, C(2)); 64.4 (À, CH2); 62.9 (‡,
C(3')); 51.8 (x, C(2')); 31.2, 31.2 (2 ‡ , MeÀC(2)); 25.8 (‡, Me3C); 23.2 (‡, MeÀC(2')); 18.3 (x, Me3C); À5.2,
‡
À5.3 (2 ‡ , Me2Si). FAB-MS: 283 (6, [M À H] ), 267 (32), 237 (25), 209 (22), 123 (30), 73 (100). HR-FAB-MS:
‡
calc. for C15H28O3Si (284.47): 284.1808 (M ); found: 284.1802.
1-[cis-3-(Hydroxymethyl)-2-methyloxiran-2-yl]dec-4-en-1-yn-3-ol (3g). From 500 mg (4.5 mmol) of 1b in
25 ml of THF, 5.9 ml (8.9 mmol) of BuLi (1.5m in hexane), and 563 mg (4.5 mmol) of (E)-oct-2-enal in 5 ml of
1
THF; yield: 692 mg (65%) of 3g. Yellow liquid. IR (neat): 3362m, 2929s, 2857s, 1653m. H-NMR (400 MHz,
CDCl3): 5.81 (m, HÀC(5)); 5.54, 5.54 (2dd, 3J(H,H) ˆ 15.3, 6.3, HÀC(4)); 4.81, 4.80 (2m, HÀC(3)); 3.82
(d, 3J(H,H) ˆ 5.5, CH2OH); 3.65 (s, OH); 3.10 (t, 3J(H,H) ˆ 5.5, HÀC(3')); 2.02 (q, 3J(H,H) ˆ 7.2, CH2(6));
1.55 (s, MeÀC(2')); 1.38 1.35 (m, CH2(7)); 1.29 1.25 (m, CH2(8), CH2(9)); 0.86 (t, 3J(H,H) ˆ 7.2, Me(10)).
13C-NMR (100 MHz, CDCl3): 134.4, 134.4 (2 ‡ , C(4)); 128.1 (‡, C(5)); 84.4, 84.4 (2x, C(2)); 82.4, 82.4 (2x,
C(1)); 63.9, 63.8 (2 ‡ , C(3')); 62.5, 62.5 (2 ‡ , C(3)); 61.8 (À, CH2OH); 52.0 (x, C(2')); 31.9, 31.3, 28.4 (3 À ,
‡
C(6), C(7), C(8)); 26.8 (‡, MeÀC(2')); 22.4 (À, C(9)); 14.0 (‡, C(10)). FAB-MS: 375 (19, [M ‡ Na] ), 351
‡
(16, [M À H] ), 295 (45), 277 (32), 203 (46), 191 (95), 161 (63), 105 (36), 73 (100). HR-FAB-MS: calc. for
‡
C14H22O3 (238.33): 261.1466 ([M ‡ Na] ); found: 261.1477.
3-(cis-3-{[(tert-Butyl)dimethylsilyloxy]methyl}-2-methyloxiran-2-yl)-1-phenylprop-2-yn-1-ol (3h). From
500 mg (2.2 mmol) of 1a in 25 ml of THF, 1.5 ml (2.2 mmol) of BuLi (1.5m in hexane), and 235 mg (2.2 mmol)
of PhCHO in 5 ml of THF; yield: 418 mg (57%) of 3h. Yellow liquid. IR (neat): 3403m, 3032w, 2929s, 2857s,
1
1472m, 1456m. H-NMR (500 MHz, C6D6): 7.51 (m, 2 arom. H); 7.23 (m, 3 arom. H); 5.33 (s, HÀC(1)); 4.04
3.95 (m, CH2); 3.03 (yt, HÀC(3')); 2.28 (s, OH); 1.40 (s, MeÀC(2')); 1.05 (s, t-Bu); 0.17, 0.17, 0.15, 0.15 (4s,
Me2Si). 13C-NMR (125 MHz, C6D6): 141.1 (x, arom. C); 128.7, 128.4, 126.8, 126.8 (4 ‡ , arom. C); 85.2 (x, C(2) or
C(3)); 84.0, 84.0 (2x, C(2) or C(3)); 64.6, 64.5, 64.5 (3 ‡ , C(1), C(3')); 63.6 (À, CH2); 51.7 (x, C(2')); 26.1
‡
(‡, Me3C); 23.1 (‡, MeÀC(2')); 18.4 (x, Me3C), À5.1, À 5.2 (2 ‡ , Me2Si). FAB-MS: 355 (6, [M ‡ Na] ), 331

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‡
(8, [M À H] ), 315 (35), 285 (28), 245 (22), 141 (100). HR-FAB-MS: calc. for C19H28O3Si (332.51): 331.1729
‡
([M À H] ); found: 331.1704.
1-(4-Bromophenyl)-3-(cis-3-{[(tert-butyl)dimethylsilyloxy]methyl}-2-methyloxiran-2-yl)prop-2-yn-1-ol
(3j). From 500 mg (2.2 mmol) of 1a in 25 ml of Et2O, 1.5 ml (2.2 mmol) of BuLi (1.5m in hexane), and 409 mg
(2.2 mmol) of 4-bromobenzaldehyde in 5 ml of Et2O; yield: 754 mg (83%) of 3j. Yellow liquid. IR (neat): 3402s,
2930s, 2857s, 1486s, 1472s. 1H-NMR (400 MHz, CDCl3): 7.74 (d, 3J(H,H) ˆ 8.3, HÀC(3), HÀC(5) of 4-
BrC6H4); 7.35 (d, 3J(H,H) ˆ 8.3, HÀC(2), HÀC(6) of 4-BrC6H4); 5.40 (s, HÀC(1)); 3.84, 3.83 (2dd, 2J(H,H) ˆ
11.8, 3J(H,H) ˆ 5.0, 1 H, CH2); 3.74 (dd, 2J(H,H) ˆ 11.8, HÀC(1), 3J(H,H) ˆ 5.2, 1 H, CH2); 3.04 (yt,
HÀC(3')); 2.83 (s, OH); 1.56 (s, MeÀC(2')); 0.88 (s, t-Bu); 0.05, 0.04 (2s, Me2Si).13C-NMR (100 MHz, CDCl3):
139.1 (x, arom. C(1)); 131.7, 131.4 (2 ‡ , arom. C(3), C(5)); 128.2, 128.1, 127.6 (3 ‡ , arom. C(2), C(6)); 122.4 (x,
arom. C(4)); 84.0, 83.9 (2x, C(2), C(3)); 64.5, 64.5, 63.6, 63.6 (4 ‡ , C(1), C(3')); 63.0 (À, CH2); 51.7 (x, C(2'));
25.8 (‡, Me3C); 23.0 (‡, MeÀC(2')); 18.2 (x, Me3C); À 5.3, À5.3 (2 ‡ , Me2Si). FAB-MS: 411/409 (2, [M À
‡
H] ), 355/353 (8), 325/323 (6), 251/249 (7), 221/219 (9), 185/183 (14), 136 (13), 73 (100). HR-FAB-MS: calc. for
‡
C19H27BrO3Si (411.41): 411.0814 ([M À H] ); found: 411.0815.
2-[2-(cis-3-{[(tert-Butyl)dimethylsilyloxy]methyl}-2-methyloxiran-2-yl)ethynyl]-7-oxabicyclo[4.1.0]-
heptan-2-ol (3k). From 500 mg (2.2 mmol) of 1a in 25 ml of THF, 1.3 ml (2.2 mmol) of BuLi (1.7m in
hexane), and 248 mg (2.2 mmol) of 2,3-epoxycyclohexanone in 5 ml of THF; yield: 578 mg (77%) of 3k.
1
Yellow oil. IR (neat): 3415s, 2933s, 2858s. H-NMR (500 MHz, CDCl3): 3.89 3.85 (m, 1 H, CH2O); 3.77
3.73 (m, 1 H, CH2O); 3.32 3.26 (m, HÀC(1), HÀC(6)); 3.02 (m, HÀC(3'')); 2.78, 2.76 (2s, OH); 1.85 1.80
(m, CH2(3)); 1.70 1.63 (m, CH2(4)); 1.54 (s, MeÀC(2')); 1.52 1.48 (m, CH2(5)); 0.88 (s, t-Bu); 0.07, 0.06
(2s, Me2Si). 13C-NMR (100 MHz, CDCl3): 84.9, 84.8 (2x, C(2')); 82.8 (x, C(1')); 67.4 (x, C(2)); 64.4, 64.3 (2 ‡
, C(3'')); 63.0 (À, CH2O); 58.0 (‡, C(1)); 55.5 (‡, C(6)); 51.6 (x, C(2'')); 34.0, 33.9 (2 À , C(3)); 25.8 (‡,
Me3C); 23.1 (‡, MeÀC(2'')); 22.1 (À, C(5)); 18.3 (À, C(4)); 18.3 (x, Me3C); À5.2, À5.3 (2 ‡ , Me2Si). FAB-
‡
‡
MS: 361 (15, [M ‡ Na] ), 337 (3, [M À H] ), 321 (20), 291 (10), 281 (6), 177 (12), 147 (16), 115 (13), 90
(45), 73 (100).
1-[2-(7-Oxabicyclo[4.1.0]hept-1-yl)ethynyl]cyclohexan-1-ol (5). From 296 mg (2.4 mmol) of 4 in 25 ml of
THF, 1.6 ml (2.4 mmol) of BuLi (1.5m in hexane), and 238 mg (2.4 mmol) of cyclohexanone in 5 ml of THF;
yield: 429 mg (81%) of 5. Yellow liquid. IR (neat): 3403s, 2935s, 2858s. 1H-NMR (500 MHz, CDCl3): 3.30 (yt,
HÀC(6'')); 2.19 (s, OH); 2.15 2.10 (m, 1 H, HÀC(2'')/HÀC(5'')); 2.00 1.94 (m, 1 H, HÀC(2'')/HÀC(5''));
1.90 1.86 (m, 4 H, HÀC(2''), HÀC(5''), HÀC(2), HÀC(6)); 1.67 1.64 (m, HÀC(2), HÀC(6)); 1.54 1.48
(m, CH2(3), CH2(4), CH2(5)); 1.47 1.29 (m, 2 H, HÀC(3'')/HÀC(4'')); 1.23 1.20 (m, 2 H, HÀC(3'')/
HÀC(4'')). 13C-NMR (125 MHz, CDCl3): 85.7, 84.6 (2x, C(1'), C(2')); 68.5 (x, C(1)); 60.0 (‡, C(6'')); 50.2
(x, C(1'')); 39.7 (À, C(2), C(6)); 29.8 (À, C(2'')/C(5'')); 25.1, 24.1 (2 À , C(3), C(4), C(5)); 23.2, 19.4, 18.8
‡
(3 À , C(2'')/C(5''), C(3''), C(4'')). FAB-MS: 203 (100, [M À OH] ).
4-(7-Oxabicyclo[4.1.0]hept-1-yl)but-3-yn-2-ol (7a). From 670 mg (5.5 mmol) of 4 in 25 ml of THF, 3.7 ml
(5.5 mmol) of BuLi (1.5m in hexane), and 242 mg (5.5 mmol) of MeCHO in 5 ml of THF; yield: 555 mg (61%)
of 7a. Yellow liquid. IR (neat): 3403s, 2983s, 2940s, 2864s. 1H-NMR (500 MHz, CDCl3): 4.50 (q, 3J(H, H) ˆ 6.7,
HÀC(2)); 3.30 (s, HÀC(6')); 2.52 (s, OH); 2.12 2.07 (m, 1 H, HÀC(2')/HÀC(5')); 1.98 1.86 (m, 3 H,
HÀC(2')/HÀC(5')); 1.41 1.20 (m, CH2(3''), CH2(4'')); 1.40 (d, 3J(H,H) ˆ 6.7, Me(1)). 13C-NMR (100 MHz,
CDCl3): 84.1, 84.0 (2x, C(3), C(4)); 60.0 (‡, C(6')); 58.1 (‡, C(2)); 50.2 (x, C(1')); 29.5 (À, C(2')/C(5')); 24.0
‡
(‡, C(1)); 24.0, 19.3, 18.7 (3 À , C(2')/C(5'), C(3'), C(4')). FAB-MS: 166 (27, M ), 149 (100). HR-FAB-MS: calc.
‡
for C10H14O2 (166.22): 166.0994 (M ); found: 166.0975.
1,1,1-Trifluoro-2-methyl-4-(7-oxabicyclo[4.1.0]hept-1-yl)but-3-yn-2-ol (7b). From 305 mg (2.5 mmol) of 4
in 25 ml of THF, 1.7 ml (2.5 mmol) of BuLi (1.5m in hexane), and 280 mg (2.5 mmol) of 1,1,1-trifluoroacetone in
5 ml of THF; yield: 335 mg (57%) of 7b. Yellow liquid. IR (neat): 3404s, 2935s, 2858s. 1H-NMR (400 MHz,
CDCl3): 3.39 (s, OH); 3.35 (t, 3J(H,H) ˆ 2.0, HÀC(2')); 2.16 2.09 (m, 1 H, HÀC(2')/HÀC(5')); 2.01 1.89
(m, 3 H, HÀC(2')/HÀC(5')); 1.60 (q, 4J(H,F) ˆ 2.8, Me); 1.41 1.20 (m, CH2(3'), CH2(4')). 13C-NMR
(100 MHz, CDCl3): 123.8 (xq, 1J(C,F) ˆ 285, CF3); 86.5 (x, C(4)); 78.0 (x, C(3)); 68.4 (xq, 2J(C,F) ˆ 33,
C(2)); 60.0 (‡, C(6')); 49.9 (x, C(1')); 29.1 (À, C(2')/C(5')); 23.9, 19.2, 18.6 (3 À , C(2')/C(5'), C(3'), C(4')); 22.9
‡
‡
(‡, C(1)). FAB-MS: 234 (80, M ), 217 (100). HR-FAB-MS: calc. for C11H13F3O2 (234.22): 234.0867 (M );
found: 234.0868.
3-(cis-3-{[(tert-Butyl)dimethylsilyloxy]methyl}-2-methyloxiran-2-yl)-1-(2,6,6-trimethylcyclohex-1-enyl)-
prop-2-yn-1-ol (9). From 500 mg (2.2 mmol) of 1a in 25 ml of THF, 1.5 ml (2.2 mmol) of BuLi (1.5m in hexane),
and 336 mg (2.2 mmol) of b-cyclocitral (8) in 5 ml of THF; yield: 569 mg (68%) of 9. Yellow liquid. IR (neat):
3439m, 2955s, 2930s, 2859s. 1H-NMR (400 MHz, C6D6): 4.98, 4.97 (2s, HÀC(1)); 3.95 (dd, 2J(H,H) ˆ 11.5,
3J(H,H) ˆ 4.5, 1 H, CH2O); 3.91, 3.90 (2dd, 2J(H,H) ˆ 11.5, 3J(H,H) ˆ 5.5, 1 H, CH2O); 2.94 (yt, HÀC(3'));

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1.98 (s, MeÀC(2')); 1.84 1.79 (m, CH2(3'')); 1.53 (s, OH), 1.47 1.40 (m, CH2(4'')); 1.38 1.31 (m, CH2(5''));
1.34, 1.34 (2s, MeÀC(4'')); 1.03, 1.01 (2s, 2 MeÀC(6'')); 0.98 (s, t-Bu); 0.13, 0.12 (2s, Me2Si). 13C-NMR (100 MHz,
C6D6): 138.2 (x, C(1'')); 133.9 (x, C(2'')); 86.8, 86.7 (2x, C(3)); 81.5 (x, C(2)); 64.7, 64.6 (2 ‡ , C(3')); 63.9, 63.5
(2 À , CH2O); 59.7 (‡, C(1)); 51.7 (x, C(2')); 39.8 (À, C(3')); 34.8 (x, C(6'')); 33.7 (À, C(3'')); 27.9 (‡,
MeÀC(6'')); 26.1 (‡, Me3C); 23.3 (‡, MeÀC(2')); 23.0 (‡, MeÀC(2'')); 18.9 (À, C(4'')); 18.5 (x, Me3C); À5.1,
‡
5.2 (2 ‡ , Me2Si). FAB-MS: 377 (2, [M À H] ), 361 (10), 287 (6), 229 (7), 187 (15), 151 (12), 123 (22), 73 (100).
‡
HR-FAB-MS: calc. for C22H38O3Si (378.63): 378.2590 (M ); found: 378.2604.
1-(cis-3-{[(tert-Butyl)dimethylsilyloxy]methyl}-2-methyloxiran-2-yl)-4-methyl-6-(2,6,6-trimethylcyclohex-
1-enyl)hex-4-en-1-yn-3-ol (11). From 500 mg (2.2 mmol) of 1a in 25 ml of THF, 1.5 ml (2.2 mmol) of BuLi (1.5m
in hexane), and 456 mg (2.2 mmol) of b-C14-aldehyde 10 [12] in 5 ml of THF; yield: 928 mg (97%) of 11. Yellow
liquid. IR (neat): 3420m, 2955s, 2928s, 2859s. 1H-NMR (400 MHz, CDCl3): 5.39 (t, 3J(H,H) ˆ 6.5, HÀC(5)); 4.73
(s, HÀC(3)); 3.87 (2dd, 2J(H,H) ˆ 11.8, 3J(H,H) ˆ 4.5, 1 H, CH2O); 3.75 (dd, 2J(H,H) ˆ 11.8, 3J(H,H) ˆ 5.3,
1 H, CH2O); 3.01 (t, 3J(H,H) ˆ 5.0, HÀC(3')); 2.72 (d, 3J(H,H) ˆ 6.5, CH2(6)); 1.97 (s, OH); 1.90 (t, 3J(H,H) ˆ
6.2, CH2(3'')); 1.77, 1.77 (2s, MeÀC(2'')); 1.55 1.52 (m, CH2(4'')); 1.54 (s, MeÀC(2')); 1.51 (s, MeÀC(4)); 1.42
1.39 (m, CH2(5'')); 0.95, 0.95 (2s, 2 MeÀC(6'')); 0.90 (s, t-Bu); 0.08, 0.08 (2s, Me2Si). 13C-NMR (100 MHz,
CDCl3): 135.7 (x, C(1'')); 132.0 (x, C(2'')); 129.7 (‡, C(5)); 128.3 (x, C(4)); 84.2, 84.1 (2x, C(1)); 82.7, 82.7 (2x,
C(2)); 68.1 (‡, C(3)); 64.5, 64.5 (2 ‡ , C(3')); 63.1 (À, CH2O); 51.7 (x, C(2')); 39.6 (À, C(5'')); 34.8 (x, C(6''));
32.8 (À, C(3'')); 28.2 (‡, MeÀC(6'')); 27.0 (À, C(6)); 25.8 (‡, Me3C); 23.2 (‡, MeÀC(2')); 19.7 (‡,
MeÀC(2'')); 19.4 (À, C(4'')); 18.2 (x, Me3C); 12.0 (‡, MeÀC(4)); À5.2, À5.3 (2 ‡ , Me2Si). FAB-MS: 455 (3,
‡
‡
[M ‡ Na] ), 431 (2, [M À H] ), 415 (8), 283 (6), 241 (12), 137 (40), 73 (100). HR-FAB-MS: calc. for C26H44O3Si
‡
(432.72): 455.2957 ([M ‡ Na] ); found: 455.2975.
This workwas supported by the Deutsche Forschungsgemeinschaft, the European Community (COST D12/
0022/99), and the Fonds der Chemischen Industrie. We thankDr. J¸rgen Fenske (F. Hoffmann-La Roche AG,
CH-Basel) for gifts of chemicals, as well as Anne Biernat and Carl Deutsch for laboratory assistance.
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Received June 6, 2002