Addition of hetero allenyl copper reagents to aldehydes: Scope and behavior

Article abstract of DOI:10.1021/jo062344z

Cyanocuprates derived from propargylic amines or ethers react with aldehydes to give regioselectively the corresponding anti-homopropargylic alcohols with a high level of diastereoselectivity. Such selectivity could be obtained independently of the nature

Full text of DOI:10.1021/jo062344z

Addition of Hetero Allenyl Copper Reagents to Aldehydes:
Scope and Behavior
Emmanuel Vrancken,*,† Nacira Alouane,† He´le`ne Ge´rard,‡ and Pierre Mangeney*,†
Institut Fe´de´ratif de Recherche FR 2769, UMR 7611, UniVersite´ Pierre et Marie Curie, 4 Place Jussieu,
F-75252, Paris Cedex, France, and Laboratoire de Chimie The´orique, UMR CNRS 7616,
UniVersite´ Pierre et Marie Curie, 4 Place Jussieu, F-75252, Paris Cedex, France
Vrancken@ccr.jussieu.fr
ReceiVed NoVember 14, 2006
Cyanocuprates derived from propargylic amines or ethers react with aldehydes to give regioselectively
the corresponding anti-homopropargylic alcohols with a high level of diastereoselectivity. Such selectivity
could be obtained independently of the nature of the heteroatom (amine or ethers) or the acetylenic
substituents. Excellent selectivities can be reached regardless of the aldehydes used, remarkably also
with vinylic or acetylenic ones. A reactivity scale for the cuprates bearing different acetylenic substituents
was established to be: SiMe3 >Ph> Et. The rate of the addition reaction to aldehydes was also found
to be slowed down in the presence of HMPA underlining the crucial role of the Li counterion. DFT
calculations have shown that the relationship between the rate and the acetylenic substituent is not
connected to a possible metallotropic equilibrium but to the stability of the reactive allenic species compared
to the less-stable propargylic isomer.
Introduction
diastereoselectivity, depending on the nature of the allenyl
moiety substituent. Excellent and general results have been
reported by Marshall for the use of isolated alkyl-substituted
allenyl tin derivatives.9 This two-step strategy was successfully
applied to R-amino10 and R-alkoxyallenylstannanes.11,12 Nev-
ertheless, due to the high functional density of homopropargylic
Reactions of allenyl metals with aldehydes to give the
corresponding homopropargylic alcohols have been studied
extensively.1 Various derivatives such as allenyl lithium,2
magnesium,3 aluminum,4 zinc,5 boron,6 cerium,7 or titanium8
have been successively tested with poor to high regio- and
(5) (a) Zweifel, G.; Hahn, G. J. Org. Chem. 1984, 49, 4565-4567. (b)
Poisson, J.-F.; Normant, J. F. J. Org. Chem. 2000, 65, 6553-6560. (c)
Chemla, F.; Ferreira, F.; Hebbe, V.; Stercklen, E. Eur. J. Org. Chem. 2002,
1385-1391. (d) Gung, B. W.; Xue, X.; Knatz, N.; Marshall, J. A.
Organometallics 2003, 22, 3158-3163. (e) Bernaud, F.; Vrancken, E.;
Mangeney, P. Synlett 2004, 1080-1082. (f) Marshall, J. A.; Ellis, K.
Tetrahedron Lett. 2004, 45, 1351-1353. (g) Marshall, J. A.; Mulheran,
J. J. Org. Lett. 2005, 7, 1593-1596. (h) Chemla, F.; Ferreira, F. Synlett
2006, 2613-2616.
† Institut Fe´de´ratif de Recherche FR 2769.
‡ Laboratoire de Chimie The´orique.
(1) (a) Yamamoto, H. In ComprehensiVe Organic Synthesis; Trost,
B. M., Fleming, I., Heathcock, C. H., Eds.; Pergamon Press: Oxford, 1991;
Vol. 2, pp 81-98. Marshall, J. A. Chem. ReV. 2000, 100, 3163-3165. (b)
Marshall, J. A.; Gung, B. W.; Grachan, M. L. In Modern Allene Chemistry;
Krause, N., Hashmi, S. K., Eds.; Willey-VCH: Weinheim, 2004; Vol. 1,
Chapter 9, pp 493-592.
(2) Mercier, F.; Epsztein, R.; Holand, S. Bull. Soc. Chim. Fr. 1972, 690-
696. Corey, E. J.; Ru¨cker, C. Tetrahedron Lett. 1982, 23, 719-722. Bour,
C.; Suffert, J. Eur. J. Org. Chem. 2006, 1390-1395.
(6) (a) Wang, K. K.; Nikam, S. S.; Ho, C. D. J. Org. Chem. 1983, 48,
5376-5377. (b) Ikeda, N.; Arai, I.; Yamamoto, H. J. Am. Chem. Soc. 1986,
108, 483-486.
(3) (a) Mercier, F.; Le Goff, N.; Epzstein, R. C. R. Hebd. Seances Acad.
Sci., Ser. C. 1974, 279, 525-528. (b) Mercier, F.; Epzstein, R. J. Organomet.
Chem. 1976, 108, 165-173. (c) Lambert, C.; Schleyer, P. v. R. Angew.
Chem., Int. Ed. Engl. 1994, 33, 1129-1140. (d) Lambert, C.; Schleyer,
P. v. R.; Wu¨rtwein, E.-U. J. Org. Chem. 1993, 58, 6377-6389. (e)
Shinokubo, H.; Miki, H.; Yokoo, T.; Oshima, K.; Utimoto, K. Tetrahedron
1995, 51, 11681-11692.
(7) Groth, U.; Kesenheimer, C.; Neidho¨fer, J. Synlett 2006, 1859-1862.
(8) Anies, C.; Lallemand, J.-Y.; Pancrazi, A. Tetrahedron Lett. 1996,
37, 5519-5522 and references therein.
(9) (a) Marshall, J. A. Chem. ReV. 1996, 96, 31-47. (b) Marshall, J. A.;
Palovich, M. R. J. Org. Chem. 1997, 62, 6001-6005. (c) Marshall, J. A.;
Ellis, K. C. Org. Lett. 2003, 5, 1729-1732 and references therein.
(10) (a) Ranslow, P. B. D.; Hegedus, L. S.; de los Rios, C. J. Org. Chem.
2004, 69, 105-111. (b) Amachtowicz, M.; Hegedus, L. S. J. Org. Chem.
2004, 69, 2229-2234.
(4) Pearson, N. R.; Hahn, G.; Zweifel, G. J. Org. Chem. 1982, 47, 3364-
3366.
10.1021/jo062344z CCC: $37.00 © 2007 American Chemical Society
Published on Web 01/26/2007
1770
J. Org. Chem. 2007, 72, 1770-1779

Addition of Hetero Allenyl Copper Reagents to Aldehydes
TABLE 1. Additions of the Copper Derivative of 1 to RCHO
FIGURE 1. Propargylic ethers 3-8.
TABLE 2. Influence of Experimental Conditions and of Oxygen
Substituent
yield
entry
R
product
anti/syna
(%)b
1
2
3
4
5
n-hexyl
c-hexyl
phenyl
propenyl
heptynyl
2a
2b
2c
2d
2e
>95:5
>95:5
>95:5
95:5
82
81
79
83
74
93:7
propargylic
ether
yield
product anti/syna (%)b
a Determined by H NMR of the crude product. Isolated yield.
1
b
entry
solvent
additive
none
none
none
12-crown-4
DBU
DMPU
HMPA
HMPA
HMPA
HMPA
1
2
3
4
5
6
7
8
9
3
3
3
3
3
3
3
4
5
6
THF
Et2O
THF
THF
THF
THF
THF
THF
THF
THF
9a
9a
9a
9a
9a
87:13
36:65
95:5c
-
96:4
95:5
97:3
96:4
94:6
95:5
68
56
65
0
70
71
65
69
75
78
alcohols, the development of a general and practical access to
this important class of compounds is still challenging. Recently,
we reported that the copper derivative of the silylated propar-
gylic amine 1 reacts cleanly with aldehydes to give regioselec-
tively the corresponding R-amino-homopropargylic alcohols
2a-e with high anti selectivity (Table 1).13 This way, a safe,
one-pot access to this class of alcohols was open. Furthermore,
this methodology was proved to be efficient even with an
enantiopure propargylic oxazolidinone.14
9a
9a
10a
11a
12a
10
a Determined by 1H NMR of the crude product. bIsolated yield.
cTransmetalation with CuCN in place of CuCN-2LiBr, diluted conditions.
The excellent regio- and diastereoselectivity of this reaction
is surprising. Indeed, such behavior is generally attributed to a
cyclic Yamamoto-Chodkiewicz transition state as the result
of the complexation of the aldehyde by a Lewis acid allenic
metallic species. According to such a transition state, it is
difficult to explain why a poorly Lewis acidic cyanocuprate is
more anti selective than the much more acidic zinc reagent.
Despite a tremendous amount of literature on organocopper
chemistry, little is known about copper reagents derived from
propargylic substrates15 and their reactivity toward aldehydes
is totally omitted. As their real structure (allenic, propargylic,
σ/π-allenic?) is unknown, all attempts of mechanistic rational-
ization remain uncertain. We have decided to investigate in
detail this reaction by studying the influence of several
parameters, namely, the nature of the heteroatom (N or O) in
the propargylic position, the nature of the acetylenic substituent,
the solvent, and the presence of additives.
Results
We first investigated the influence of the heteroatom by using
propargylic ethers instead of amines. The starting ether deriva-
tives 3-8 (Figure 1) are prepared with good yields by classical
reactions starting from the commercially available propargyl
alcohol (see Experimental Section).
The study on ethers was initiated using the t-Bu O-substituted
derivative 3 as the model substrate. Its treatment at -90 °C
with s-BuLi or t-BuLi in THF and subsequent transmetalation
with the soluble CuCN-2LiBr complex followed by the addition
of CyCHO at the same temperature gave regioselectively the
homopropargylic alcohol 9a with an 87:13 anti/syn selectivity
(Table 2, entry 1), a slightly lower ratio than what is obtained
with an amine derivative13 (Table 1).
The possible influence of reaction parameters was then
checked, and the results are summarized in Table 2 (entries
1-6).
(11) Savall, B. M.; Powel, N. A.; Roush, W. R. Org. Lett. 2001, 3, 3057-
3060.
(12) Scheidt, K. A.; Bannister, T. D.; Tasaka, A.; Wendt, M. D.; Savall,
B. M.; Fegley, G. J.; Roush, W. R. J. Am. Chem. Soc. 2002, 124, 6981-
6990.
(13) Bernaud, F.; Vrancken, E.; Mangeney, P. Org. Lett. 2003, 5, 2567-
2569.
The H-Li exchange, impossible with the amine 1 in Et2O
as solvent, occurs easily when propargylic ethers are used. In
this solvent, reversal selectivity is observed, the syn isomer being
the major one (Table 2, entry 2). In THF, a dilution two times
and a decrease of the amount of lithium salts (transmetalation
with CuCN instead of CuCN-2LiBr) result in a significant
improvement of the anti/syn ratio (Table 2, entries 1 and 3).
These observations led us to examine the effect of lithium-
chelating additives such as DBU, DMPU, and HMPA (Table
2, entries 5-7). A beneficial influence of these additives on
the diastereoselectivity (anti/syn up to 97:3) is observed.
Noteworthy is that no reaction occurs when 12-crown-4 is added
to the reaction mixture (Table 2, entry 4). The optimized
conditions (HMPA as the additive) were applied with success
to the methoxy ether 4 (Table 2, entry 8). Similarly, under these
(14) Alouane, N.; Bernaud, F.; Marrot, J.; Vrancken, E.; Mangeney, P.
Org. Lett. 2005, 7, 5797-5800.
(15) For the use of propargyl-allenyl copper(I) reagents, see: (a) Ganem,
B. Tetrahedron Lett. 1974, 4467-4470. (b) Commec¸ron, A.; Normant, J.;
Villieras, J. J. Organomet. Chem. 1975, 93, 415-421. (c) Michelot, D.;
Linstrumelle, G. Tetrahedron Lett. 1976, 275-276. (d) Ruitenberg, K.;
Kleijn, H.; Meijer, J.; Oostveen, E. A.; Vermeer, P. J. Organomet. Chem.
1982, 224, 399-405. (e) Ruitenberg, K.; Vermeer, P. J. Organomet. Chem.
1983, 256, 175-180. de Graaf, W.; Boersma, J.; van Koten, G.
J. Organomet. Chem. 1989, 378, 115-124. (f) Bednarski, P. J.; Nelson,
S. D. J. Med. Chem. 1989, 32, 203-213. (g) Rozema, M. J.; Knochel, P.
Tetrahedron Lett. 1991, 32, 1855-1858. Lam, H. W.; Pattenden, G. Angew.
Chem., Int. Ed. 2002, 41, 508-511.
J. Org. Chem, Vol. 72, No. 5, 2007 1771

Vrancken et al.
TABLE 4. Addition of the Copper Derivative of 7 to RCHOa
TABLE 3. Addition of a Copper Derivative of 5 to RCHOa
yield
(%)c
yield
(%)c
entry
R
product
anti/synb
entry
R
product
anti/synb
1
2
3
4
5
c-hexyl
n-Pr
phenyl
propenyl
heptynyl
13a
13b
13c
13d
13e
97:3
90:10
96:4
>97:3
96:4
78
74
78
76
76
1
2
3
4
5
6
n-Pr
i-Pr
t-Bu
phenyl
propenyl
heptynyl
11b
11c
11d
11e
11f
90:10
94:6
>97:3
97:3
>97:3
96:4
79
78
72
88
83
79
a All reactions are performed during 16 h in THF at -60 °C (see the
11g
general procedure in the Experimental Section). bDetermined by 1H NMR
a All reactions are performed during 30 min in THF at -90 °C with
c
of the crude product. Isolated yield.
HMPA as an additive (see the general procedure in the Experimental
Section). bDetermined by 1H NMR of the crude product. Isolated yield.
c
SCHEME 1
conditions, the MOM and MIP ether derivatives 5 and 6 afford
the corresponding homopropargylic alcohols 11a and 12a16 with
a diastereomeric ratio close to 95:5 (Table 2, entries 9 and 10).
The steric hindrance of the oxygen substituent has poor influence
on the diastereoselectivity (Table 2, entries 7-10), although a
sterically driven transition state is commonly mentioned to
rationalize the anti stereochemistry.17 Furthermore, the presence
of chelating protective groups does not affect the regioselectivity
because no trace of allenic products are detected in the crude
mixtures.
SCHEME 2
We next screened the reaction of the MOM ether derivative
5 with a representative set of aldehydes (Table 3).
In all cases, anti-ether alcohols 11b-g (Table 3, entries 1-6)
are obtained in good yields. The stereoselectivities are in the
same range as those reported by Roush when a tin derivative is
used11 (94:6 to >97:3, entries 2-6), except in the case of
butyraldehyde which gives a lower 90:10 anti/syn ratio (Table
3, entry 1). Noteworthy are the results obtained with crotonal-
dehyde and octynal. Indeed, no product arising from a conjugate
addition is detected with these unsaturated aldehydes (Table 3,
entries 5 and 6). Moreover, these aldehydes give rise to a high
level of selectivity despite their small size.
The possible influence of the nature of the triple-bound
substituent was studied. Accordingly, the reactivity of the copper
derivative of the ethyl-substituted propargylic ether 7 on CyCHO
was screened. In the presence of HMPA, no reaction is observed
at -90 °C. An increase of the reaction’s temperature to
-50 °C gives after 5 days only a trace amount of the desired
anti-homopropargylic alcohol 13a. This lack of reactivity of
the copper derivative of 7 is in good accordance with Roush’s
observations,11 no reaction being observed toward aldehydes
with the tin derivative of 7. In our case, a dramatic change is
observed when the reaction is performed without HMPA, the
attempted product 13a being obtained in 16 h at -60 °C with
a good selectivity (Scheme 1). Its anti stereochemistry is
assigned by a nOe analysis of the oxazolidinone 14 obtained
by charcoal-promoted ring-closing carbonylation18 of the cor-
responding diol (Scheme 2).
Addition of the copper derivative of 7 to various aldehydes
occurs with good yields and selectivities (Table 4) notably with
unsaturated aldehydes (entries 3-5).
The same study was performed on the phenyl analogue 8,
and the obtained results are reported in Table 5.
As previously observed for analogues 3-7, the addition of
aldehydes to the copper derivative of 8 proceeds cleanly to
afford regio- and stereoselectively anti-propargylic alcohols
15a-c. The kinetics of this reaction (75% conversion after 1 h
at -80 °C, 100% at -60 °C after 10 min) stands in between
the one of silicon derivative 5 (a few minutes at -90 °C) and
the one of ethyl derivative 7 (16 h at -60 °C; compare Table
2 and Scheme 1). Moreover, in this case, the reaction takes place
even in the presence of HMPA but is dramatically slowed: 4 h
is required to ensure the completion with roughly the same
stereoselectivity.
Obviously, the reactivity of copper derivatives depends on
the nature of the acetylenic substituent of the starting propargylic
ether. To confirm the generality of this observation, the study
was extended to the corresponding ethyl and phenyl amine
(16) Noteworthy compound 12a gives cleanly the corresponding diol
22 after stirring overnight in CHCl3 at room temperature (see Experimental
Section).
(17) Epzstein, R. The Formation and Transformations of Allenic and
R-Acetylenic Carbanions. In ComprehensiVe Carbanions Chemistry; Buncel,
E., Durst, T., Eds.; Elsevier: Amsterdam, 1984; Vol. B, pp 107-175.
(18) Alouane, N.; Boutier, A.; Baron, C.; Vrancken, E.; Mangeney, P.
Synthesis 2006, 885-889.
1772 J. Org. Chem., Vol. 72, No. 5, 2007

Addition of Hetero Allenyl Copper Reagents to Aldehydes
SCHEME 3. Chemical Correlation of 18a
FIGURE 2. Propargylic amines 16 and 17.
TABLE 5. Addition of a Copper Derivative of 8 to RCHO
SCHEME 4. Hydrolysis Experiments
yield
product anti/syna (%)b
entry
R
additive
1
2
3
4
c-hexyl
c-hexyl
phenyl
HMPA (4 h, -60 °C)
none (-60 °C, 10′)
none (-60 °C, 10′)
15a
15a
15b
15c
>97:3
>97:3
>97:3
95:5
90
93
82
95
1
a Determined by H NMR of the crude mixture.
propenyl none
nature of the heteroatom (N or O), or the nature of the acetylenic
substituent (SiMe3, Ph, Et). Such regioselectivity fits well with
the existence of an allenyl intermediate, as they are known to
react with aldehydes through a Se’-type mechanism. The
acetylenic substituent effect is more surprising. The observed
reactivity scale for the ether derivatives 5, 8, and 7 toward
aldehydes is: SiMe3 > Ph >> Et. Similarly, for the amine
analogues, the silicon derivative 1 was found to be much more
reactive than the phenyl one (17). Thus, the less-stabilized
allenyl anions are the less-reactive ones! It could be tempting
to correlate this reactivity order with the real structure of the
copper reagents in solution, which could depend on the nature
of the acetylenic substituent, as reported by Reich for the Li
analogues.19 We reasoned that hydrolysis experiments could give
some indications of the structural differences among ether
derivatives 5Cu, 7Cu, and 8Cu (Scheme 4).
When treated by H2O, 5Cu affords exclusively the initial
propargylic ether 5, as already observed for amine derivatives.
In contrast, hydrolysis of the copper derivatives 7Cu and 8Cu
furnishes exclusively the allenic ethers 20 and 21 (Scheme 4).20
This behavior toward water is quite surprising, suggesting a
structural difference in solution for these three copper species.
We thus decided to perform DFT calculations to get insight
into the real nature of the reactive organometallic species.
The allenic vs propargylic nature of some ether derivatives
in solution is examined for various substituents, R, as described
in Table 7.
As shown in the second column of Table 7 (X ) H), the
regioselectivity of hydrolysis reactions can be fully explained
on the basis of the stability of the final products. Indeed, the
allene B(R,H) is found to be the most stable species for R ) H
or R ) CH3 by 8.0 and 4.1 kcal mol-1, respectively. In opposite,
the propargylic form A(R,H) is favored for the Si-substituted
compounds by 4.1 and 4.2 kcal mol-1 for R ) SiH3 or R )
SiMe3, respectively (Table 7, column 2).
Because hydrolysis is commonly considered as irreversible,
and thus not thermodynamically controlled, the stability of the
copper derivatives is also examined (Table 7, columns 3-5).
Whatever the nature of the copper reagent (X ) Cu, CuCN-,
1
b
a Determined by H NMR of the crude product. Isolated yield
TABLE 6. Addition of a Copper Derivative of 17 to RCHO
yield
entry
R
product
anti/syna
(%)b
1
2
3
cyclohexyl
phenyl
propenyl
18a
18b
18c
>97:3
>97:3
95:5
91
86
80
1
b
a Determined by H NMR of the crude product. Isolated anti product
derivatives 16 and 17 (Figure 2). These two compounds are
obtained, as their ether analogues, from the propargyl amine
(see Experimental Section).
The ethyl derivative 16 was subjected to metalation using
several lithium bases. Unfortunately, the deprotonation takes
place mainly (s-BuLi) or exclusively (t-BuLi) on the alkyl-
substituted propargylic position, as confirmed by deuteration
experiments. With the copper derivative of amine 17, the
addition of representative aldehydes is totally regioselective,
affording cleanly aminoalcohols 18a-c with excellent stereo-
selectivity (Table 6). The anti stereochemistry of 18a was
determined by chemical correlation from 2b and comparison
with the NMR spectra of 18a (Scheme 3). As already observed
for the ether analogue, the kinetics of the reaction is significantly
slowed by the presence of the phenyl group (no reaction at
-90 °C, 10 min at -40 °C for the phenyl derivative compared
to a few minutes at -80 °C for the silicon analogue).
Discussion
(19) (a) Reich, H.; Holladay, J. J. Am. Chem. Soc. 1995, 117, 8470-
8471. (b) Reich, H.; Holladay, J.; Mason, E.; Sikorski, W. J. Am. Chem.
Soc. 1995, 117, 12137-12150. (c) Reich, H.; Holladay, J.; Walker, T.;
Thompson, J. J. Am. Chem. Soc. 1999, 121, 9769-9780.
(20) The metalation of propargylic ether 5 was checked by a deuterolysis
experiment.
Some general features can be brought forward from this study.
First of all, the homopropargylic alcohol is exclusively obtained
when copper reagents react with aldehydes whichever the
experimental conditions (solvents, additives, temperature), the
J. Org. Chem, Vol. 72, No. 5, 2007 1773

Vrancken et al.
TABLE 7. ∆E (in kcal mol-1) for Various Substituents and
Migrating Atoms
substituent, the allenic form being preferred in all cases, as
shown by the R angle. Clearly, there is a relationship between
the observed reactivity scale and the allenic character of these
anion moieties, the more propargylic one being the more
reactive. Nevertheless, according to the regio- and diastereo-
selectivity observed in the reaction with aldehydes, as well as
the relative calculated stabilities, it seems reasonable to invoke
allenes as the reactive species.
The effect of the substituent R on the nucleophilicity of the
allenic complex B(R,Cu) was further examined by the mean
of the Fukui nucleophilicity indexes23 associated to the atomic
basin24 for C3 (see Figure 3). It was found to be larger for the
SiH3-substituted species (0.24) than for the CH3 analogue (0.20,
the 0.4 difference being significant because the Fukui indexes
over all the molecules sum to 1), in full accordance with the
experimental reactivity scale, as measured from reaction time
and temperature. The larger nucleophilicity of the silylated allene
is thus fully justified from electronic properties as a simple
copper adduct, without invoking a metal ancillary ligand, lithium
coordination, or solvent, aldehyde, or steric effects (because the
SiH3 entity was used).
The second important and general observation is the inclina-
tion for anti selectivity exhibited by all copper reagents. On
the basis of the above postulated allenic structure of the reactive
species, this selectivity could be rationalized by a classical
Yamamoto-Chodkiewicz cyclic transition state, involving the
minimization of nonbonding interactions. In our case, a fully
sterically driven model is not sufficient to rationalize the
selectivity. For example, in the case of propargylic ethers 5 and
7, the use of unsaturated aldehydes (Table 3, entries 4-6, and
Table 4, entries 3-5) gives better selectivities than the more
sterically hindered butyraldehyde (Table 3, entry 1, and Table
4, entry 2). In the same manner, it would be difficult to explain
the excellent anti selectivity obtained by changing the silyl
substituent to an Et or Ph only by steric interactions. In this
last case, the main difference lies in their reaction rate, the less-
reactive species being the most selective one. Similarly, the use
of diluted conditions resulted in a significant improvement of
the selectivity (Table 2, entry 3). All this information shows
that the diastereoselectivity is also rate dependent, the best
selectivities being obtained for slow reactions. The rates of the
reactions are dramatically slowed or even stopped in the
presence of HMPA (compare reaction rates for Et- or Ph-
substituted ether derivatives 7 and 8 in the presence or absence
of HMPA; Scheme 1 and Table 5, entries 1 and 2). Apparently,
HMPA would act as a rate depletion agent by squeezing the
lithium counterion.25 Therefore, it is now possible to rationalize
the solvent effect, the anti selectivity increasing with the lithium
complexation ability of the solvent, from Et2O to a THF/HMPA
mixture. Results obtained in the presence of HMPA show that
only traces of the lithium counterion are sufficient to promote
the reaction, but in this case, the rate is noticeably reduced.
X/R
H
Cu
Cu(CN)-
Cu(CN)Li
H
CH3
SiH3
SiMe3
-8.0
-4.1
+4.1
+4.2
-10.7
-8.5
-3.0
-1.6
-13.8
-8.4
-5.9
-4.6
-14.2
-10.3
-9.3
-8.4
or CuCNLi) and whatever the nature of the R substituent, the
allenic form B(R,X) is found to be the most stable structure.
Although the preference for the allenic structure is not very
pronounced for some neutral complexes (B(SiMe3,Cu), for
instance), it becomes clearly favored as soon as a cyano ligand
is added on copper (B(R,CuCN) or B(R,CuCNLi)).
The stability scale observed for the allenyl copper derivatives
follows the same trends as the above B(R,H) series: R ) H >
CH3 > SiH3 > SiMe3. This trend was investigated on the basis
of the geometrical and electronic structure of the allenes,
considered as an anionic [R-CdCdCHOMe]- moiety (R )
H, CH3, SiH3, and SiMe3; Figure 3). A single minimum is
obtained for each allenic moiety, where the R-C-C angle (so-
called R(R)) indicates a structure intermediate between an allenic
(120°) and a propargylic (180°) form. The following order is
found for this angle: R(H) ) 118.5° < R(Me) ) 124.8° <
R(SiH3) ) 135.1° < R(SiMe3) ) 138.6°. It is thus possible to
connect the stability of the organocopper species on the
increased allenic character of the organic moiety.
The influence of the nature of the R substituent on the
propargylic character as well as of the propargylic proportion
on the stability of the copper species was investigated for R )
CH3 and R) SiH3 on the basis of a topological analysis of the
electron localization function (ELF).21
The larger propargylic character in the case of SiH3 compared
to CH3 can be explained by the delocalization of the lone pair
on C1 by the SiH3 moiety. A monosynaptic basin associated to
an electron lone pair on C1 is located in both [R-CdCd
CHOMe]- moieties (R ) CH3 and SiH3).22 Whatever the nature
of the substituent, the population on this basin (C1) is more
abundant than that on the C3 position (see Figure 3). Moreover,
a decrease of the electron population is observed for R ) SiH3
(1.70 electrons) compared to CH3 (2.02 electrons). Coordination
of a copper-centered fragment (Cu+ or CuCN) will thus be
favored in the more electron-rich case, namely, for CH3-
substituted species vs SiH3-substituted ones. This can be
confirmed by computation of the Cu-C bonding basin popula-
tion in B(CH3-Cu) (1.99 electrons, corresponding to a full
single bond) or B(SiH3-Cu) (1.80 electrons, slightly depopu-
lated). At the same time, the presence of the SiH3 group leads
to an electron transfer from the acetylenic bond in A(SiH3,Cu)
to the C-Si bond compared to the R ) CH3 case.
(22) The chemical meaning of ELF basins can be obtained from: Noury,
S.; Krokidis, X.; Fuster, F.; Silvi, B. Comput. Chem. (Oxford) 1999, 23,
597-604.
(23) (a) Parr, R. G.; Yang, W. J. Am. Chem. Soc. 1984, 106, 4049-
4050. (b) Yang, W.; Parr, R. G. Proc. Natl. Acad. Sci. U.S.A. 1985, 82,
6723-6726.
As predicted by these calculations, the anionic [R-CdCd
CHOMe]- moieties stand in between an allenic and a propar-
gylic structure, depending on the nature of the acetylenic
(24) (a) Cioslowski, J.; Martinov, M. J. Phys. Chem. 1993, 97, 10948-
10951. (b) Tiznado, W.; Chamorro, E.; Contreras, R.; Fuentealba, P. J. Phys.
Chem. A 2005, 109, 3220-3224.
(25) For a similar effect, see: (a) Nielsson, K.; Andersson, T.; Ullenius,
C.; Gerold, A.; Krause, N. Chem.-Eur. J. 1998, 4, 2051-2058. (b)
Woodward, S. Chem. Soc. ReV. 2000, 29, 393-401.
(21) (a) Silvi, B.; Savin, A. Nature 1994, 371, 683-686. (b) Savin, A.;
Silvi, B.; Colonna, F. Can. J. Chem. 1996, 74, 1088-1096.
1774 J. Org. Chem., Vol. 72, No. 5, 2007

Addition of Hetero Allenyl Copper Reagents to Aldehydes
FIGURE 3. ELF isocontours (isosurface ) 0.84) for [R-CdCdCHOMe]- moieties (R ) CH3, left; R ) SiH3, right), basin population (in electrons),
and the two mesomeric forms showing the presence of a lone pair basin on both C1 and C3.
contrast, a strong dependence between the rate and the acetylenic
substituent has been underlined. DFT calculations have shown
that these differences are not connected to metallotropic
equilibrium constants but rather to the inherent stability of the
allenic forms, which is therefore the predominant species. The
use of additives such as HMPA or 12-crown-4 has pointed out
the crucial role of the lithium counterion as the activating agent,
FIGURE 4. Postulated transition state.
even in a catalytic amount.
From a synthetic point of view, hetero allenyl-copper species
are promising reagents. Whatever the aldehyde, their addition
gives a one-pot, straightforward, and general access to the
corresponding anti-homopropargylic alcohols with qualitatively
similar levels of induction as the tin strategy. Noteworthy is
that this methodology allows the efficient preparation of anti-
alkyl-substituted homopropargylic ether alcohols, which were
found to be inaccessible by the tin chemistry.
This underlines the crucial activating effect of the lithium in
these transformations, which is confirmed by the total lack of
reactivity observed when 12-crown-4 is used as the additive
(entry 4, Table 2). The dramatic role of the lithium counterion
does not fit with the Yamamoto-Chodkiewicz cyclic transition
state,17 where the allenic metal ensures the activation of the
aldehyde through its own Lewis acidity. When this is not the
case, the use of a Lewis acid leads to a change of the transition
state from a cyclic to an open one, giving rise to the formation
of the syn isomer. In this case, there is no connection between
the metal and the Lewis acid, which is distant from the allenic
moiety. The allenic copper reagents would thus exhibit an
original mode of reaction: in the present case, the lithium would
offset the lack of Lewis acidity of the copper, while standing
closely associated with it through the CN ligand (Figure 4).26
Experimental Section
Computational Details. Full geometry optimizations were
carried out without symmetry constraints using the Gaussian 03
program within the framework of the DFT (B3LYP),27 using the
6-31+G** basis set for all atoms. Analysis of the electron
localization function was carried out using the TopMod Package.28
The conventional color code is used for the representation of the
basins: blue for protonated disynaptic basins, green for bonding
pair disynaptic basins, and red for lone pair monosynaptic basins.
General Considerations. Experiments were carried out under
a dry argon atmosphere. All glassware was dried at 120 °C and
assembled while hot under a stream of argon. All moisture-sensitive
reactants were handled under an argon atmosphere. Low-temper-
ature experiments were carried out by cooling a three-necked round-
Conclusion
This work represents the first general study on the addition
of heterosubstituted allenyl cyanocuprate reagents onto alde-
hydes. Various copper reagents derived from propargylic ethers
or amines and bearing a silyl, an alkyl, or a phenyl group in
the acetylenic position have been tested. They all react in a
similar fashion, whatever the nature of the heteroatom (amine
or ether), yielding exclusively homopropargylic alcohols. In
(27) (a) Becke, A. D. J. Phys. Chem. 1993, 98, 5648-5652. (b) Lee,
C.; Yang, W.; Parr, R. G. Phys. ReV. B 1988, 37, 785-789. (c) Becke,
A. D. Phys. ReV. A: At., Mol., Opt. Phys. 1988, 38, 3098-3100.
(28) Noury, S.; Krokidis, X.; Fuster, F.; Silvi, B. TopMod Package, 1997.
This package is available on the Web site of the Laboratoire de Chimie
The´orique, Universite´ Pierre et Marie Curie (UMR CNRS/UPMC 7616),
URL: www.lct.jussieu.fr/silvi.
(26) For the structure of cyanocuprates, see: (a) Bertz, S. J. Am. Chem.
Soc. 1991, 113, 5470-5471. (b) Boche, G.; Boseld, F.; Marsch, M.; Harms,
K. Angew. Chem., Int. Ed. 1998, 37, 1684-1686.
J. Org. Chem, Vol. 72, No. 5, 2007 1775

Vrancken et al.
bottom flask with an ether/acetone (-80/-90 °C) bath, frozen with
liquid nitrogen. The flask was equipped with an internal thermom-
eter, a nitrogen inlet, and a septum cap. Tetrahydrofuran was
distilled from sodium-benzophenone ketyl. Column chromatogra-
phies were performed over silica gel Si 0.040-0.063 mesh. Melting
points are uncorrected. 1H NMR spectra were recorded at 400 MHz,
and 13C NMR spectra were recorded at 100 MHz, in CDCl3 or
C6D6 as solvent. Chemical shifts are reported in ppm (reference
TMS for 1H NMR and CDCl3 or C6D6 for 13C NMR). Compounds
3, 4,29 5,30 6,31and anti-11c-f11 have already been described.
1-(Methoxymethoxy)-pent-2-yne (7) and 1-(3-(Methoxymeth-
oxy)prop-1-ynyl)benzene (8). To a stirred solution of propargyl
alcohol (11.7 mL, 200 mmol) in dimethoxymethane (200 mL) were
added at room temperature lithium bromide (3.5 g, 20 mmol) and
toluenesulfonic acid (3.5 g, 20 mmol). Stirring was continued for
24 h. The mixture was treated with water and extracted with ether
(2 × 20 mL). The organic layers were combined, dried over sodium
sulfate, filtered off, and concentrated in vacuo. Distillation of the
residue (82-84 °C, 10 mmHg) gave 15 g (75%) of methoxymethyl
ether as a colorless liquid.
reaction was stirred an additional 30 min at -80 °C. The reaction
media turned yellow, and a solution of HMPA (2.8 mL, 16 mmol)
in THF (5 mL) was added dropwise at -80 °C, followed by the
aldehyde (2.2 mmol). After 30 min at -90 °C, the reaction was
quenched by the addition of an aqueous NH4Cl/NH3 (2:1) solution
and extracted with diethyl ether (3 × 20 mL). The combined organic
layers were washed with water and brine, dried over magnesium
sulfate, and filtered off. The solvents were removed in vacuo, and
the product was then subjected to FC (flash chromatography) on
SiO2.
anti-2-tert-Butoxy-1-cyclohexyl-4-trimethylsilanyl-but-3-yn-
1-ol (anti-9). This compound was prepared according to the general
procedure A, using (3-tert-butoxy-prop-1-ynyl)trimethylsilane 3 (2
mmol, 368 mg) and cyclohexane carboxaldehyde (0.266 mL, 2.2
mmol). Purification by FC (pentane/Et2O 95:5) gave a mixture of
homopropargylic alcohols anti-9 and syn-9 (383 mg, 65%) as a
pale yellow oil. The diastereoselectivity of the reaction was
1
determined by H NMR to be 97:3. anti-9: IR (neat) ν ) 3550
(br), 2972, 2924, 2852, 1450, 1391, 1366, 1249, 1190, 1057, 840,
759 cm-1; 1H NMR (400 MHz) δ 4.23 (d, J ) 4.6 Hz, 1H), 3.32-
3.28 (m, 1H), 2.40 (d, J ) 3.5 Hz, 1H), 2.01-1.98 (m, 1H), 1.78-
1.58 (m, 6H), 1.27 (s, 9H), 1.24-1.04 (m, 4H), 0.17 (s, 9H); 13C
NMR (100 MHz) δ 105.0, 90.9, 78.1, 75.7, 64.5, 39.8, 29.4, 28.4,
28.3, 26.6, 23.3, 26.0, 0.0. Elemental anal. calcd for C17H32O2Si:
C, 68.86; H, 10.88; O, 10.79. Found: C, 68.91; H, 10.72. syn-9
A solution of methoxymethyl propargyl ether (15 g, 150 mmol)
in THF (150 mL) cooled to -80 °C was treated dropwise with
nBuLi (2.3 M in hexane, 150 mmol), maintaining the internal
temperature below -80 °C. The mixture was stirred for 1 h at
-80 °C. EtI (13.5 mL, 165 mmol) was added dropwise at -80 °C.
The reaction mixture was then allowed to warm to room temperature
and refluxed for 3 h. The reaction was quenched using a saturated
aqueous solution of ammonium chloride. The layers were separated.
The aqueous phase was extracted with ether, and the combined
organic phases were dried over magnesium sulfate and filtered off.
The volatiles were removed under reduced pressure, and the residue
was purified by fractional distillation under reduced pressure (10
mmHg, 77 °C) to yield 17.1 g (85%) of 7 as a colorless oil. IR
(neat) ν ) 2938 (br), 2287, 2227, 2714, 1450, 1320, 1148, 1041,
1
(only the distinguishable H NMR peaks are reported): 1H NMR
(400 MHz) δ 4.08 (d, J ) 7.8 Hz, 1H), 3.39-3.34 (m, 1H), 2.53
(d, J ) 2.3 Hz, 1H), 1.30 (s, 9H).
anti-1-Cyclohexyl-2-methoxy-4-trimethylsilanyl-but-3-yn-1-
ol (anti-10a). This compound was prepared according to the general
procedure A, using (3-methoxy-1-propynyl)trimethylsilane 4 (2
mmol, 284 mg) and cyclohexane carboxaldehyde (0.266 mL, 2.2
mmol). Purification by FC (pentane/Et2O 85:15) gave pure ho-
mopropargylic alcohol anti-10a (350 mg, 69%) as a pale yellow
oil. The diastereoselectivity of the reaction was determined to be
96:4. anti-10a: IR (neat) ν ) 3452 (br), 2924, 2852, 2169, 1738,
1449, 1365, 1249, 1217, 1084, 1021, 840, 760 cm-1; 1H NMR (400
MHz) δ 4.05 (d, J ) 4.3 Hz, 1H), 3.48-3.44 (m, 4H), 2.21 (d,
J ) 4,2 Hz, 1H), 2.02-1.99 (m, 1H), 1.78-1.59 (m, 5H), 1.31-
1.04 (m, 5H), 0.21 (s, 9H); 13C NMR (100 MHz) δ 101.0, 93.3,
76.5, 56.9, 40.1, 29.1, 28.5, 26.5, 25.9, 0.0. Elemental anal. calcd
for C14H26O2Si: C, 66.09; H, 10.30; O, 12.58. Found: C, 66.13;
1
990, 920 cm-1; H NMR (400 MHz) δ 4.45 (s, 2H), 3.95 (s, 2H),
3.13 (s, 3H), 2.03-1.99 (m, 2H), 0.93 (t, J ) 7.3 Hz, 3H); 13C
NMR (100 MHz) δ 94.6, 88.3, 74.7, 55.5, 54.7, 13.7,12.4.
Elemental anal. calcd for C7H12O2: C, 65.60; H, 9.44; O, 24.97.
Found: C, 65.52; H, 9.48.
The compound 8 was prepared as follows: A solution of
methoxymethyl propargyl ether (5 g, 50 mmol), 1-iodobenzene (5.6
mL, 50 mmol), and freshly distilled triethylamine (2 mL) in THF
(20 mL) was added dropwise to a solution of CuI (560 mg) and
Pd(PPh3)2Cl2 (700 mg) in THF (20 mL). The reaction was stirred
for 12 h, hydrolyzed with NH3/NH4Cl (2:1) solution, and extracted
with ether. The combined organic layers were washed with brine,
dried over anhydrous magnesium sulfate, filtered off, and concen-
trated in vacuo. Purification by FC (pentane/Et2O 95:5) gave 7.6 g
(86%) of 8 as a colorless oil. IR (neat) ν ) 2850, 1489, 1148,
1099, 1041, 989, 919, 755, 690 cm-1; 1H NMR (CDCl3, 400 MHz)
1
H, 10.46. syn-10a (only the distinguishable H NMR peaks are
reported): 1H NMR (400 MHz) δ 3.93 (d, J ) 7.3 Hz, 1H).
anti-1-Cyclohexyl-2-methoxymethoxy-4-trimethylsilanyl-but-
3-yn-1-ol (anti-11a). This compound was prepared according to
the general procedure A, using (3-(methoxymethoxy)-1-propynyl)-
trimethylsilane 5 (2 mmol, 344 mg) and cyclohexane carboxalde-
hyde (0.266 mL, 2.2 mmol). Purification by FC (pentane/Et2O 85:
15) gave pure homopropargylic alcohol anti-11a (426 mg, 75%)
as a pale yellow oil. The diastereoselectivity of the reaction was
determined by 1H NMR to be 94:6. anti-11a: IR (neat) ν ) 3490
δ 7.48-7.32 (m, 5H), 4.80 (s, 2H), 4.47 (s, 2H), 3.44 (s, 3H); 13
C
NMR (CDCl3, 100 MHz) δ 131.8, 128.5, 128.3, 122.6, 94.8, 86.1,
84.6, 55.6, 54.8. Elemental anal. calcd for C11H12O2: C, 74.98; H,
6.86; O, 18.16. Found: C, 74.58; H, 6.69.
(br), 2923, 2852, 2181, 1450, 1250, 1152, 1099, 840, 759 cm-1
;
1H NMR (400 MHz) δ 4.98 (d, J ) 6.8 Hz, 1H), 4.66 (d, J ) 6.8
Hz, 1H), 4.47 (d, J ) 4.4 Hz, 1H), 3.47 (dt, J ) 4.3, 7.1 Hz, 1H),
3.41 (s, 3H), 2.27 (d, J ) 4.3 Hz, 1H), 2.05-2.02 (m, 1H), 1.80-
1.66 (m, 5H), 1.30-1.06 (m, 5H), 0.20 (s, 9H); 13C NMR (100
MHz) δ 100.7, 94.2, 93.2, 76.9, 68.6, 56.0, 40.2, 29.3, 28.4, 26.5,
26.3, 26.0, 0.0. Elemental anal. calcd for C15H28O3Si: C, 63.33;
H, 9.92; O, 16.87. Found: C, 63.21; H, 9.99. syn-11a (only the
distinguishable 1H NMR peaks are reported): 1H NMR (400 MHz)
δ 4.98 (d, J ) 6.8 Hz, 1H), 4.66 (d, J ) 6.8 Hz, 1H), 4.35 (d, J )
6.32 Hz, 1H), 3.39 (s, 3H), 2.49 (d, J ) 3.1 Hz, 1H), 0.19 (s, 9H).
anti-3-Methoxymethoxy-1-trimethylsilanyl-hept-1-yn-4-ol (anti-
11b). This compound was prepared according to the general
procedure A, using (3-(methoxymethoxy)-1-propynyl)trimethylsi-
lane 5 (2 mmol, 344 mg) and butyraldehyde (0.200 mL, 2.1 mmol).
Purification by FC (pentane/Et2O 85:15) gave a mixture of
homopropargylic alcohols anti-11b and syn-11b (386 mg, 79%)
General Procedure A for the Addition of Copper Reagents
Derived from Propargylic Ethers 3-6 to Aldehydes. A solution
of propargylic ether (2 mmol) in THF (15 mL) cooled to -90 °C
was treated dropwise with t-BuLi (1.5 M in hexane, 2.1 mmol),
maintaining the internal temperature below -88 °C. The mixture
was stirred for 1 h at -90 °C, during which an orange color
developed. A solution of CuCN (270 mg, 3 mmol) and LiBr (521
mg, 6 mmol) in THF (10 mL) was then added dropwise, and the
(29) Labaudinie`re, L.; Hanaizi, J.; Normant, J.-F. J. Org. Chem. 1992,
57, 6903-6908.
(30) Shikhiev, I. A.; Ibragimov, V. A.; Kraev, S. F. J. Gen. Chem. USSR
1971, 41, 617-619.
(31) Uchida, K.; Utimoto, K.; Nozaki, H. Tetrahedron 1977, 33, 2987-
2992.
1776 J. Org. Chem., Vol. 72, No. 5, 2007

Addition of Hetero Allenyl Copper Reagents to Aldehydes
as a pale yellow oil. The diastereoselectivity of the reaction was
determined by 1H NMR to be 90:10. anti-11b: IR (neat) ν ) 3467
(br), 2958, 2172, 1250, 1153, 1024, 840, 760 cm-1; 1H NMR (400
MHz) δ 4.98 (d, J ) 6.1 Hz, 1H), 4.68 (d, J ) 6.1 Hz, 1H), 4.33
(d, J ) 4.1 Hz, 1H), 3.77-3.71 (m, 1H), 3.42 (s, 3H), 2.25 (d,
J ) 5.6 Hz, 1H), 1.62-1.41 (m, 4H), 0.97 (t, J ) 7.8 Hz, 3H),
0.20 (s, 9H); 13C NMR (100 MHz) δ 100.7, 94.5, 93.2, 72.8, 70.9,
56.0, 34.8, 19.0, 14.2, 0.0. Elemental anal. calcd for C12H24O3Si:
C, 58.97; H, 9.90; O, 19.64. Found: C, 58.57; H, 9.89. syn-11b
homopropargylic alcohols anti-13a and syn-13a (375 mg, 78%) as
a pale yellow oil. The diastereoselectivity of the reaction was
determined by 1H NMR to be 97:3. anti-13a: IR (neat) ν ) 3455
(br), 2922, 2851, 2231, 1450, 1151, 1096, 1021, 918 cm-1; 1H NMR
(400 MHz) δ 4.97 (d, J ) 6.7 Hz, 1H), 4.64 (d, J ) 6.7 Hz, 1H),
4.64 (dt, J ) 2.0, 3.8 Hz, 1H), 3.43 (ddd, J ) 3.7, 4.0, 7.4 Hz,
1H), 3.38 (s, 3H), 2.31 (d, J ) 4 Hz, 1H), 2.24 (dq, J ) 4.0, 7.6
Hz, 2H), 2.06-2.02 (m, 1H), 1.71-1.48 (m, 5H), 1.33-1.29 (m,
3H), 1.16 (t, J ) 7.4 Hz, 3H), 1.39-1.00 (m, 2H); 13C NMR (100
MHz) δ 12.5, 13.9, 25.8, 26.1, 26.4, 28.5, 29.1, 40.0, 55.7, 68.3,
74.0, 77.0, 90.1, 93.8; Elem anal. Calcd for C14H24O3: C, 69.96;
H, 10.07; O, 19.97. Found: C, 70.11; H, 9.99. syn-13a: only the
distinguishable 1H NMR peaks are reported: 1H NMR (400 MHz)
δ 4.98 (d, J ) 6.8 Hz, 1H), 4.27 (dt, J ) 2.0, 6.6 Hz, 1H).
anti-5-Methoxymethoxy-non-6-yn-4-ol (anti-13b). This com-
pound was prepared according to the general procedure B, using
butyraldehyde (0.200 mL, 2.1 mmol). Purification by FC (pentane/
Et2O 80:20) gave pure homopropargylic alcohol anti-13b (296 mg,
74%) as a pale yellow oil. The diastereoselectivity of the reaction
was determined by 1H NMR to be 90:10. anti-13b: IR (neat) ν )
1
(only the distinguishable H NMR peaks are reported): 1H NMR
(400 MHz) δ 4.16 (d, J ) 7.1 Hz, 1H).
anti-3-Methoxymethoxy-1-trimethylsilanyl-undeca-1,5-diyn-
4-ol (anti-11g). This compound was prepared according to the
general procedure A, using (3-(methoxymethoxy)-1-propynyl)-
trimethylsilane 5 (2 mmol, 344 mg) and 2-octynal (0.314 mL, 2.1
mmol). Purification by FC (pentane/Et2O 85:15) gave pure ho-
mopropargylic alcohol anti-11g (480 mg, 79%) as a pale yellow
1
oil. The diastereoselectivity of the reaction was determined by H
NMR to be 96:4. anti-11g: IR (neat) ν ) 3425 (br), 2932, 2237,
2175, 1249, 1151, 1101, 1026, 840, 760 cm-1; 1H NMR (400 MHz)
δ 4.94 (d, J ) 6.8 Hz, 1H), 4.72 (d, J ) 6.8 Hz, 1H), 4.50 (ddt,
J ) 2.0, 3.8, 8.1 Hz, 1H), 4.45 (d, J ) 3.8 Hz, 1H), 3.44 (s, 3H),
2.75 (d, J ) 8.1 Hz, 1H), 2.24 (dt, J ) 2.0, 7.1 Hz, 2 H), 1.57-
1.50 (m, 2H), 1.44-1.26 (m, 4H), 0.91 (t, J ) 7.1 Hz, 3H), 0.18
(s, 9H); 13C NMR (100 MHz) δ 100.0, 95.0, 93.3, 87.3, 77.5, 71.4,
65.2, 56.1, 31.2, 28.4, 22.4, 19.0, 14.2, 0.0. Elemental anal. calcd
for C16H28O3Si: C, 64.82; H, 9.52; O, 16.19. Found: C, 64.49; H,
9.67. syn-11g (only the distinguishable 1H NMR peaks are
reported): 1H NMR (400 MHz) δ 4.36 (d, J ) 6.3 Hz, 1H).
anti-1-Cyclohexyl-2-(1-methoxy-1-methyl-ethoxy)-4-trimeth-
ylsilanyl-but-3-yn-1-ol (anti-12a). This compound was prepared
according to the general procedure A, using [3-(1-methoxy-1-
methyl-ethoxy)-prop-1-ynyl]trimethylsilane 6 (2 mmol, 400 mg)
and cyclohexane carbaldehyde (0.266 mL, 2.2 mmol). Purification
by FC (pentane/Et2O 90:10) gave a mixture of homopropargylic
alcohols anti-12a and syn-12a (487 mg, 78%) as a pale yellow oil.
The diastereoselectivity of the reaction was determined by 1H NMR
to be 95:5. anti-12a: IR (neat) ν ) 3496 (br), 2990, 2923, 2852,
3457 (br), 2958, 2851, 2205, 1318, 1150, 1098, 1022, 919 cm-1
;
1H NMR (400 MHz) δ 4.95 (d, J ) 6.8 Hz, 1H), 4.65 (d, J ) 6.8
Hz, 1H), 4.31 (dt, J ) 1.8, 3.8 Hz, 1H), 3.74-3.68 (m, 1H), 3.39
(s, 3H), 2.33 (d, J ) 5.0 Hz, 1H), 2.26 (dq, J ) 2.0, 7.6 Hz, 2H),
1.64-1.32 (m, 4H), 1.15 (t, J ) 7.6 Hz, 3H), 0.95 (t, J ) 7.0 Hz,
3H); 13C NMR (100 MHz) δ 94.0, 90.1, 74.1, 72.9, 70.5, 55.7,
34.7, 18.9, 14.0, 13.8, 12.4. Elemental anal. calcd for C11H20O3:
C, 65.97; H, 10.07; O, 23.97. Found: C, 65.75; H, 10.14. syn-13b
1
(only the distinguishable H NMR peaks are reported): 1H NMR
(400 MHz) δ 4.98 (d, J ) 6.8 Hz, 1H), 4.27 (dt, J ) 2.0, 6.6 Hz,
1H).
anti-2-Methoxymethoxy-1-phenyl-hex-3-yn-1-ol (anti-13c). This
compound was prepared according to the general procedure B, using
benzaldehyde (0.230 mL, 2.1 mmol). Purification by FC (pentane/
Et2O 80:10) gave a mixture of homopropargylic alcohols anti-13c
and syn-13c (375 mg, 78%) as a pale yellow oil. The diastereose-
1
lectivity of the reaction was determined by H NMR to be 96:4.
anti-13c: IR (neat) ν ) 3449 (br), 2888, 2231, 1454, 1149, 1097,
2172, 1450, 1374, 1310, 1250, 1210, 1184, 1072, 838, 758 cm-1
;
1025, 916.7, 751, 699 cm-1; H NMR (400 MHz) δ 4.92 (d, J )
1
1H NMR (400 MHz) δ 4.50 (d, J ) 3.5 Hz, 1H), 3.36 (dt, J ) 4.0,
8.1 Hz, 1H), 3.25 (s, 3H), 2.31 (d, J ) 4.3 Hz, 1H), 2.10-2.07 (m,
1H), 1.78-1.52 (m, 5H), 1.48 (s, 3H), 1.38 (s, 3H), 1.28-1.01
(m, 5H), 0.18 (s, 9H); 13C NMR (C6D6, 100 MHz) δ 105.2, 101.9,
90.8, 78.1, 64.2, 49.3, 40.6, 29.4, 29.3, 27.0, 26.6, 26.4, 25.9, 24.8,
0.0. Elemental anal. calcd for C17H32O3Si: C, 65.33; H, 10.32; O,
15.36. Found: C, 65.53; H, 10.40. syn-12a (only the distinguishable
1H NMR peaks are reported): 1H NMR (400 MHz) δ 4.32 (d, J )
7.6 Hz, 1H), 3.42 (m, 1H), 3.29 (s, 3H), 1.49 (s, 3H), 1.41 (s, 3H).
General Procedure B for the Addition of a Copper Reagent
Derived from Propargylic Ether 7 to Aldehydes. A solution of
propargylic ether 7 (256 mg, 2 mmol) in THF (15 mL) cooled to
-90 °C was treated dropwise with tBuLi (1.5 M in hexane, 2.1
mmol), maintaining the internal temperature below -88 °C. The
mixture was stirred for 1 h at -90 °C, during which an orange
color developed. A solution of CuCN (270 mg, 3 mmol) and LiBr
(521 mg, 6 mmol) in THF (10 mL) was then added dropwise, and
the reaction was stirred an additional 30 min at -80 °C. The
reaction media turned yellow, and the aldehyde (2.2 mmol) was
added dropwise. After 16 h at -60 °C, the reaction mixture was
quenched by the addition of an aqueous NH4Cl/NH3 (2:1) solution
and extracted with diethyl ether (3 × 20 mL). The combined organic
layers were washed with water and brine, dried over magnesium
sulfate, and filtered off. The solvents were removed in vacuo, and
the product was then subjected to FC (flash chromatography) on
SiO2.
6.7 Hz, 1H), 4.82 (dd, J ) 4.0, 4.4 Hz, 1H), 4.61 (d, J ) 6.7 Hz,
1H), 4.64 (dt, J ) 2.0, 5.0 Hz, 1H), 3.21 (s, 3H), 2.91 (d, J ) 4.0
Hz, 1H), 2.24 (dq, J ) 4.0, 7.6 Hz, 2H), 1.14 (t, J ) 7.6 Hz, 3H);
13C NMR (100 MHz) δ 139.6, 128.0, 126.9, 93.9, 90.8, 75.4, 74.1,
71.6, 55.6, 13.7, 12.5. Elemental anal. calcd for C14H18O3: C, 71.77;
H, 7.74; O, 20.49. Found: C, 71.36 H, 8.01. syn-13c (only the
distinguishable 1H NMR peaks are reported): 1H NMR (400 MHz)
δ 4.99 (d, J ) 6.0 Hz, 1H), 4.76 (dd, J ) 2.7, 7.2 Hz), 4.37 (dt,
J ) 1.8, 7.2 Hz, 1H), 3.33 (s, 3H), 2.16 (dq, J ) 1.8, 7.3 Hz, 2H),
1.07 (t, J ) 7.3 Hz, 3H).
anti-5-Methoxymethoxy-non-2-en-6-yn-4-ol (anti-13d). This
compound was prepared according to the general procedure B, using
crotonaldehyde (0.180 mL, 2.1 mmol). Purification by FC (pentane/
Et2O 75:25) gave pure homopropargylic alcohol anti-13d (299 mg,
76%) as a pale yellow oil. The diastereoselectivity of the reaction
was determined by 1H NMR to be >97:3. anti-13d: IR (neat) ν )
3449 (br), 2287, 2231, 1451, 1318, 1151, 1097, 1023, 964 cm-1
;
1H NMR (400 MHz) δ 5.80 (dq, J ) 6.6, 15.4 Hz, 1H), 5.60 (ddd,
J ) 1.8, 6.8, 15.4 Hz, 1H), 4.93 (d, J ) 6.8 Hz, 1H), 4.66 (d, J )
6.8 Hz, 1H), 4.33 (dt, J ) 2.0, 3.8 Hz, 1H), 4.17 (m, 1H), 3.38 (s,
3H), 2.55 (d, J ) 5.8 Hz, 1H), 2.25 (dq, J ) 2.0, 7.6 Hz, 2H), 1.74
(ddd, J ) 0.8, 0.8, 6.8 Hz, 3H), 1.15 (t, J ) 7.6 Hz, 3H); 13C
NMR (100 MHz) δ 129.4, 128.9, 94.2, 90.2, 74.2, 74.1, 70.7, 55.8,
17.9, 13.8, 12.5. Elemental anal. calcd for C11H18O3: C, 66.64; H,
9.15; O, 24.21. Found: C, 66.97; H, 9.55.
anti-5-Methoxymethoxy-trideca-3,7-diyn-6-ol (anti-13e). This
compound was prepared according to the general procedure B, using
2-octynal (0.314 mL, 2.1 mmol). Purification by FC (pentane/Et2O
80:20) gave a mixture of homopropargylic alcohols anti-13e and
syn-13e (408 mg, 76%) as a pale yellow oil. The diastereoselectivity
anti-1-Cyclohexyl-2-methoxymethoxy-hex-3-yn-1-ol (anti-
13a). This compound was prepared according to the general
procedure B, using cyclohexane carboxaldehyde (0.266 mL, 2.2
mmol). Purification by FC (pentane/Et2O 85:15) gave a mixture of
J. Org. Chem, Vol. 72, No. 5, 2007 1777

Vrancken et al.
1
of the reaction was determined by H NMR to be 96:4. anti-13e:
Elemental anal. calcd for C18H18O3: C, 76.57; H, 6.43; O, 17.00.
Found: C, 76.33; H, 6.81.
IR (neat) ν ) 3432 (br), 2932, 2235, 1318, 1149, 1100, 1025, 919
cm-1; H NMR (400 MHz) δ 4.94 (d, J ) 6.8 Hz, 1H), 4.70 (d,
1
anti-(E)-3-(Methoxymethoxy)-1-phenylhept-5-en-1-yn-4-ol (anti-
15c). This compound was prepared according to the general
procedure C, using crotonaldehyde (0.09 mL, 1.1 mmol). Purifica-
tion by FC (pentane/Et2O 80:20) gave a mixture of homopropargylic
alcohol anti-15c and syn-15c (230 mg, 95%) as a yellow oil. The
diastereoselectivity of the reaction was determined by 1H NMR to
be 95:5. IR (neat) ν ) 3422 (br), 2887, 1489, 1442, 1350, 1210,
J ) 6.8 Hz, 1H), 4.48-4.42 (m, 2H), 3.42 (s, 3H), 2.82 (d, J )
7.6 Hz, 1H), 2.29-2.21 (m, 4H), 1.56-1.48 (m, 2H), 1.41-1.28
(m, 4H), 1.16 (t, J ) 7.3 Hz, 3H), 0.89 (t, J ) 7.3 Hz, 3H); 13C
NMR (100 MHz) δ 94.5, 90.2, 86.9, 77.30, 73.8, 71.0, 65.3, 55.8,
30.9, 28.2, 22.2, 18.7, 13.9, 13.7, 12.5. Elemental anal. calcd for
C15H24O3: C, 71.39; H, 9.59; O, 19.02. Found: C, 70.99; H, 9.58.
syn-13e (only the distinguishable 1H NMR peaks are reported): 1H
NMR (400 MHz) δ 4.36 (dt, J ) 2.0, 6.0 Hz, 1H).
1
1150, 1097, 917 cm-1; H NMR (CDCl3, 400 MHz) δ 7.45-7.28
(m, 5H), 5.87 (dq, 1H, J ) 8.8, 16.4 Hz), 5.71 (dq, 1H, J ) 1.5,
8.8, 16.4 Hz), 5.03 (d, 1H, J ) 6.8 Hz), 4.74 (d, 1H, J ) 6.8 Hz),
4.60 (d, 1H, J ) 3.8 Hz), 4.33 (q, 1H, J ) 5.6, 10.4 Hz), 3.45 (s,
3H), 2.73 (d, 1H, J ) 5.6 Hz), 1.78 (d, 3H, J ) 5.6 Hz); 13C NMR
(CDCl3, 100 MHz) δ 131.9, 129.7, 128.7, 128.6, 128.3, 122.3, 94.5,
87.7, 84.3, 74.2, 70.9, 55.9, 17.9. Elemental anal. calcd for
C15H18O3: C, 73.15; H, 7.37; O, 19.49. Found: C, 73.08; H, 7.38.
syn-15c (only the distinguishable 1H NMR peaks are reported): 1H
NMR (400 MHz) δ 4.43 (q, 1H, J ) 7.1 Hz, 1H).
Structure Determination of anti-13a: Preparation of 14. anti-
13a (165 mg, 0.69 mmol) and anhydrous PPTS (1.73 g, 6.9 mmol)
in t-BuOH (5 mL) were boiled under argon during 24 h. Water
was added to the cooled solution, and the aqueous layer was
extracted with ether. The ether layer was washed with water, dried,
and evaporated. The crude product was then transformed into the
corresponding oxazolidinone 14 according to ref 18. IR (neat) ν )
2926 (br), 2854, 2359, 2340, 2243, 1802, 1450, 1350, 1143, 1083,
1000, 769, 726 cm-1; H NMR (400 MHz) δ 5.27 (td, J ) 2.0,
1
N,N-Dibenzyl-3-phenylprop-2-yn-1-amine (17). A solution of
N,N-dibenzyl-prop-2-yn-1-amine (5 g, 21 mmol), 1-iodobenzene
(2.4 mL, 21 mmol), and freshly distilled triethylamine (0.8 mL) in
THF (10 mL) was added dropwise to a solution of CuI (238 mg)
and Pd(PPh3)2Cl2 (322 mg) in THF (10 mL). When the reaction
was completed, the mixture was hydrolyzed with an aqueous NH3/
NH4Cl (1:3) solution and diluted with ether. The combined organic
layers were washed with brine and dried over anhydrous magnesium
sulfate and filtered off. The solvent was evaporated in vacuo, and
the product was isolated by chromatography (pentane/Et2O 95:5)
to yield 5.7 g (88%) of 17 as a yellow solid (mp 62 °C). IR (neat)
4.3, 7.1 Hz, 1H), 4.29 (dd, J ) 7.1, 8.8 Hz, 1H), 2.29 (dq, J ) 2.0,
7.3, 9.6 Hz, 2H), 2.07-1.68 (m, 10H), 1.18 (t, J ) 7.6 Hz, 3H);
13C NMR (100 MHz) δ 154.2, 93.9, 82.9, 70.7, 70.4, 38.8, 28.6,
28.1, 25.9, 25.3, 25.1, 13.3, 12.5. Elemental anal. calcd for
C17H26O3: C, 73.34; H, 9.41; O, 17.24. Found: C, 73.45; H, 9.40.
General Procedure C for the Addition of Copper Reagents
Derived from Propargylic Ethers 8 and Amines 17 to Aldehydes.
A solution of a propargylic derivative (1 mmol) in THF (20 mL)
cooled to -90 °C was treated dropwise with tBuLi (1.5 M in
hexane, 1.1 mmol), maintaining the internal temperature below
-88 °C. The mixture was stirred for 1 h at -90 °C, during which
an orange color developed. A solution of CuCN (135 mg, 1.5 mmol)
and LiBr (261 mg, 3 mmol) in THF (5 mL) was then added
dropwise, and the reaction was stirred an additional 30 min at
-80 °C. The reaction media turned yellow, and the aldehyde (1.1
mmol) was added dropwise. After stirring for 45 min at -60 or
-40 °C, the reaction mixture was quenched by the addition of an
aqueous NH4Cl/NH3 (2:1) solution and extracted with diethyl ether
(3 × 20 mL). The combined organic layers were washed with water
and brine, dried over magnesium sulfate, and filtered off. The
solvents were removed in vacuo, and the product was then subjected
to FC (flash chromatography) on SiO2.
ν ) 2824, 1488, 1454, 1351, 1310, 755, 738 cm-1 1H NMR
;
(CDCl3, 400 MHz) δ 7.78-7.50 (m, 15H), 4.03 (s, 4H), 3.74 (s,
2H); 13C NMR (CDCl3, 100 MHz) δ 139.2, 132.1, 129.4, 128.6,
128.3, 127.4, 86.2, 84.7, 57.9, 42.3. Elemental anal. calcd for
C23H21N: C, 88.71; H, 6.80; N, 4.50. Found: C, 88.71; H, 6.72;
N, 4.49.
anti-1-Cyclohexyl-2-(dibenzylamino)-4-phenylbut-3-yn-1-ol
(anti-18a). This compound was prepared according to the general
procedure C, using cyclohexane carboxaldehyde (0.13 mL, 1.1
mmol). Purification by FC (pentane/Et2O 90:10) gave pure ho-
mopropargylic alcohol anti-18a (385 mg, 91%) as a yellow oil.
The diastereoselectivity of the reaction was determined by 1H NMR
to be >97:3. anti-18a: IR (neat) ν ) 3448 (br), 2923, 2360, 1489,
anti-1-Cyclohexyl-2-(methoxymethoxy)-4-phenylbut-3-yn-1-
ol (anti-15a). This compound was prepared according to the general
procedure C, using cyclohexane carboxaldehyde (0.13 mL, 1.1
mmol). Purification by FC (pentane/Et2O 80:20) gave pure ho-
mopropargylic alcohol anti-15a (268 mg, 93%) as a yellow oil.
The diastereoselectivity of the reaction was determined by 1H NMR
to be >97:3. anti-15a: IR (neat) ν ) 3475 (br), 2922, 2850, 1357,
1150, 1097, 1022, 917 cm-1; 1H NMR (CDCl3, 400 MHz) δ 7.49-
7.28 (m, 5H), 5.07 (d, 1H, J ) 6.8 Hz), 4.72 (dd, 2H, J ) 6.8, 4.0
Hz), 3.62-3.44 (m, 1H), 3.44 (s, 3H), 2.47 (d, 1H, J ) 4.0 Hz),
2.11 (d, 1H, J ) 12.9 Hz), 1.80-1.73 (m, 5H), 1.29-1.09 (m,
5H); 13C NMR (CDCl3, 100 MHz) δ 131.9, 128.6, 128.3, 122.4,
94.2, 87.7, 84.2, 76.8, 68.6, 55.9, 40.1, 29.1, 28.6, 26.4, 26.1, 25.9.
Elemental anal. calcd for C18H24O3: C, 74.97; H, 8.39; O, 16.64.
Found: C, 74.61; H, 8.41.
1
1449, 1070, 745 cm-1; H NMR (CDCl3, 400 MHz) δ 7.61-7.28
(m, 15H), 3.82 (d, 2H, J ) 13.6 Hz), 3.80 (d, 1H, J ) 7.8 Hz),
3.79-3.66 (m, 1H), 3.58 (d, 2H, J ) 13.6 Hz), 2.01 (d, 1H, J )
4.6 Hz), 1.89-0.94 (m, 11H); 13C NMR (CDCl3, 100 MHz) δ
139.4, 132.1, 129.2, 128.5, 128.4, 127.2, 122.9, 87.9, 85.3, 75.9,
56.1, 56.0, 39.2, 30.7, 26.9, 26.5, 26.3, 24.8. Elemental anal. calcd
for C30H33NO3: C, 85.06; H, 7.85; N, 3.31; O, 3.78. Found: C,
84.76; H, 7.75; N, 3.29.
anti-(2-Dibenzylamino)-1,4-diphenylbut-3-yn-1-ol (anti-18b).
This compound was prepared according to the general procedure
C, using benzaldehyde (0.12 mL, 1.1 mmol). Purification by FC
(pentane/Et2O 90:10) gave pure homopropargylic alcohol anti-18b
(356 mg, 86%) as a yellow oil. The diastereoselectivity of the
1
reaction was determined by H NMR to be >97:3. anti-18b: IR
(neat) ν ) 3398 (br), 3027, 2974, 1490, 1453, 1026, 975 cm-1; 1H
NMR (CDCl3, 400 MHz) δ 7.71-7.24 (m, 20H), 4.97 (d, 1H, J )
7.8 Hz), 4.09 (d, 1H, J ) 8.1 Hz), 4.00 (d, 2H, J ) 13.6 Hz), 3.64
(d, 2H, J ) 13.6 Hz), 2.96 (s, 1H); 13C NMR (CDCl3, 100 MHz)
δ 141.2, 138.9, 132.2, 128.9, 128.6, 128.5, 128.4, 128.2, 128.1,
127.5, 127.2, 122.9, 88.3, 84.9, 74.7, 59.9, 55.9. Elemental anal.
calcd for C30H27NO: C, 86.30; H, 6.52; N, 3.35; O, 3.83. Found:
C, 86.28; H, 6.59; N, 3.41.
anti-(E)-3-(Dibenzylamino)-phenylhept-en-1-yn-4-ol (anti-
18c). This compound was prepared according to the general
procedure C, using crotonaldehyde (0.09 mL, 1.1 mmol). Purifica-
tion by FC (pentane/Et2O 80:20) gave pure homopropargylic alcohol
anti-(1S,2R)-2-(Methoxymethoxy)-1,4-diphenylbut-3-yn-1-ol
(anti-15b). This compound was prepared according to the general
procedure C, using benzaldehyde (0.12 mL, 1.1 mmol). Purification
by FC (pentane/Et2O 70:30) gave pure homopropargylic alcohol
anti-15b (231 mg, 82%) as a yellow oil. The diastereoselectivity
of the reaction was determined by 1H NMR to be >97:3. anti-15b:
IR (neat) ν ) 3449 (br), 2890, 2360, 1490, 1453, 1149, 1099, 917
cm-1; 1H NMR (CDCl3, 400 MHz) δ 7.54-7.28 (m, 5H), 5.02 (d,
1H, J ) 6.8 Hz), 4.98 (t, 1H, J ) 8.6 Hz), 4.77 (d, 1H, J ) 4.8
Hz), 4.71 (d, 1H, J ) 6.8 Hz), 3.29 (s, 3H), 3.02 (d, 1H, J ) 3.5
Hz); 13C NMR (CDCl3, 100 MHz) δ 139.4, 131.9, 128.7, 128.3,
128.2, 128.1, 126.9, 122.2, 94.3, 88.3, 84.0, 75.5, 71.9, 55.8.
1778 J. Org. Chem., Vol. 72, No. 5, 2007

Addition of Hetero Allenyl Copper Reagents to Aldehydes
anti-18c (304 mg, 80%) and syn-18c (10 mg, 2.6%) as yellow oils.
The diastereoselectivity of the reaction was determined by 1H NMR
to be 95:5. anti-18c: IR (neat) ν ) 3419 (br), 3060, 2913, 1489,
Hz). 21: 1H NMR (400 MHz) δ 7.49-7.28 (m, 5H), 7.03 (d, 1H
J ) 5.8 Hz), 6.79 (d, 1H, J ) 5.8 Hz), 4.91 (s, 2H), 3.50 (s, 3H).
1-Cyclohexyl-4-trimethylsilanyl-but-3-yne-1,2-diol (22). anti-
12a was dissolved in CDCl3 and stirred at room temperature
overnight to give pure diol 22 without further purification. IR (neat)
ν ) 3378 (br), 2922, 2852, 2171, 1449, 1405, 1248, 1035, 962,
1
1452, 1070, 961 cm-1; H NMR (CDCl3, 400 MHz) δ 7.62-7.28
(m, 15H), 5.89-5.83 (m, 1H), 5.64 (dq, 1H, J ) 1.5, J ) 6.6, 15.2
Hz), 4.34-4.31 (m, 1H), 3.99 (d, 2H, J ) 13.6 Hz), 3.77 (d, 1H,
J ) 7.6 Hz), 3.57 (d, 2H, J ) 13.6 Hz), 2.55 (s, 1H), 1.83 (d, 3H,
J ) 6.6 Hz); 13C NMR (CDCl3, 100 MHz) δ 139.3, 132.1, 131.3,
129.0, 128.4, 128.3, 127.2, 122.9, 87.8, 84.7, 72.9, 58.2, 56.0, 17.9.
Elemental anal. calcd for C27H27NO: C, 85.00; H, 7.13; N, 3.67;
O, 4.19. Found: C, 85.08; H, 7.14; N, 3.73.
1
839, 758 cm-1; H NMR (400 MHz) δ 4.42 (d, J ) 3.5 Hz, 1H),
3.34 (dd, J ) 3.8, 10.8 Hz, 1H), 2.03 (d, 1H, J ) 12.9 Hz), 1.76-
0.98 (m, 11H), 0.17 (s, 9H); 13C NMR (100 MHz) δ 51.9, 90.2,
40.3, 26.8, 26.2, 25.9, 25.6, 13.5. Elemental anal. calcd for
C13H24O2Si: C, 64.95; H, 10.06; O, 13.31; Si, 11.68. Found: C,
64.65; H, 10.46.
syn-18c: IR (neat) ν ) 3429 (br), 3027, 2920, 1489, 1452, 1070,
1
963 cm-1; H NMR (CDCl3, 400 MHz) δ 7.52-7.28 (m, 15H),
5.86 (dq, 1H, J ) 6.6, 3.6 Hz), 5.41 (dq, 1H, J ) 1.8, 6.6, 13.6
Acknowledgment. We thank Clariant for financial support
to N.A. We also thank Prof. J. Normant for many interesting
discussions. We thank Prof. B. Silvi for fruitful assistance.
Calculations have been performed on the IBM SP4 supercom-
puters at CRIHAN (Saint Etienne du Rouvray, France).
1
Hz), 4.16 (dd, 1H, J ) 6.8, 9.6 Hz), 4.03 (s, 1H), 3.98 (d, 2H,
J ) 13.4 Hz), 3.55 (d, 2H, J ) 13.4 Hz), 3.47 (d, 1H, J ) 9.9 Hz),
1.72 (dd, 3H, J ) 1.5, 6.6 Hz); 13C NMR (CDCl3, 100 MHz) δ
138.2, 131.8, 129.8, 129.2, 128.6, 128.4, 127.5, 122.9, 87.7, 83.6,
71.1, 58.6, 55.1, 17.9.
1-Methoxymethoxy-penta-1,2-diene (20) and (3-Meth-
oxymethoxy-propa-1,2-dienyl)-benzene (21). These compounds
were obtained by hydrolysis of the corresponding copper derivatives
and were analyzed without further purification. 20: 1H NMR (400
MHz) δ 6.58 (dt, 1H, J ) 2.5, 5.8 Hz), 5.88 (q, 1H, J ) 5.8 Hz),
4.80 (s, 2H), 3.42 (s, 3H), 2.17-2.04 (m, 2H), 1.03 (t, 3H, J ) 7.3
Supporting Information Available: 1H and 13C NMR spectra
of 7-10, 11a,b,g, 12a, 13a-e, 14, 15a-c, 17, 18a-c, and 22.
This material is available free of charge via the Internet at
http://pubs.acs.org.
JO062344Z
J. Org. Chem, Vol. 72, No. 5, 2007 1779