Three-carbon homologation of diorganozincs with lithiated acetylenic epoxides

Article abstract of DOI:10.1021/jo302128n

Reaction of dialkylzincs with lithiated acetylenic epoxides is described to give zincates that undergo a 1,2- metallate rearrangement by an anti-SN2 pathway. This rearrangement occurs with the transfer of an alkyl or a silyl group affording allenylzinc in

Full text of DOI:10.1021/jo302128n

Article
pubs.acs.org/joc
Three-Carbon Homologation of Diorganozincs with Lithiated
Acetylenic Epoxides
Aurelien Denichoux, Laurent Debien, Mathieu Cyklinsky, Malika Kaci, Fabrice Chemla,* Franck Ferreira,*
́
and Alejandro Perez-Luna
́
́ ́
Institut Parisien de Chimie Moleculaire, Institut de Chimie Moleculaire (FR 2769), UPMC-Univ Paris 6, UMR CNRS 7201, Case
183, 4 place Jussieu, F-75252 Paris Cedex 05, France
S
* Supporting Information
ABSTRACT: Reaction of dialkylzincs with lithiated acetylenic
epoxides is described to give zincates that undergo a 1,2-
metallate rearrangement by an anti-SN2′ pathway. This
rearrangement occurs with the transfer of an alkyl or a silyl
group affording allenylzinc intermediates. Allenic and/or
homopropargylic alcohols are obtained upon hydrolysis.
Quenching the reaction mixture with aldehydes or ketones is shown to give access to 2-alkynyl-1,3-diols in a stereoselective
manner.
Scheme 2. Preparation of an Enantioeneriched Allenylboron
INTRODUCTION
■
Allenylmetals are versatile reagents intensively used in organic
synthesis.1 The preparation of allenylmetals (with boron,
copper, tin, indium, or zinc as the metal) through the direct
SN2′ substitution reaction of metallic reagents to propargylic
substrates bearing a leaving group at the propargylic position is
well-documented (Scheme 1, path A).2 Conversely, little is
Scheme 1. Three-Carbon Homologation with Propargylic
Substrates
Allenyl aluminums4c and zirconiums7 have been analogously
obtained from propargylic chlorides, mesylates, or tosylates.
Moreover, allenylzincs 3 have been generated by the three-
carbon homologation of lithium triorganozincates, a process
that involves the intermediate formation of alkynylogous zinco-
carbenoids undergoing a 1,2-migration (Scheme 3).8
Allenylzincs 3 are particularly interesting and have been
reacted with several electrophiles to provide allenes 4 (via an
SE2 pathway)7a or homopropargylic 57b as well as propargylic
alcohols 67c (via an SE2′ pathway).
A related reaction involving an acetylenic epoxide and
lithium tributylzincate was described by Marshall in 1994
(Scheme 4).9,10 However, unlike propargylic mesylates, in this
case, the reaction was evidenced to proceed to some extent (ca.
25%) by direct SN2′ displacement, thus without intermediate
formation of an alkynylogous zinco-carbenoid. Deuterated
allenic alcohol 8 was indeed obtained (through an SE2 process)
upon quenching of the allenylzinc intermediate 7 with D2O
with only ca. 75% D-incorporation.
known on the alternate preparation of allenylmetals by the 1,2-
metallate rearrangement of alkynylogous carbenoids of type 1.3
The overall process leading to allenylmetals 2 involves the
initial formation of 1 through metalation at the acetylenic
terminus and the subsequent 1,2-migration of the R3
substituent with displacement of the leaving group through
an SN2′ pathway (Scheme 1, path B).
Despite this promising preliminary result, no other example
of the use of acetylenic epoxides for three-carbon homologation
of organozinc reagents has been reported to date. We thus
In seminal works, this approach was successfully applied to
the preparation of allenylborons from propargylic chlorides,4
acetates,4d,5 acetals,6 or mesylates.4d An enantioenriched
allenylboron could be obtained with a good level of selectivity
from an enantiopure chiral propargylic mesylate as the result of
the stereoselective transfer of a dimethylphenylsilyl group
through an anti-SN2′ mechanism (Scheme 2).4d
Special Issue: Robert Ireland Memorial Issue
Received: September 28, 2012
Published: December 4, 2012
© 2012 American Chemical Society
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Marshall’s case due to the disfavored isomerization of 7 into
α,α,α-trisubstituted propargylzinc 7′. Conversely, in our case,
isomerization of allenylzinc 11 into α,α-disubstituted prop-
argylzinc 11′ should be more favorable, leading to a mixture of
alcohols 10a and 10a′ upon hydrolysis, through an SE2′ process
(Scheme 7).13
Scheme 3. Preparation and Use of Allenylzincs by Three-
Carbon Homologation of Lithium Triorganozincates with
Propargylic Mesylates
Although the diastereomeric ratio of allenic isomer 10a could
not be determined, two diastereomers could be observed by
13C NMR.
Analogous results were obtained with a similar procedure at
−20 °C (Table 1, entry 3). Interestingly, when dibutylzinc
(nBu2Zn) was preformed prior to the addition to Li-9a, by
mixing 1 equiv of ZnBr2 and 2 equiv of nBuLi (giving
nBu2Zn·2LiBr), upon hydrolysis a significantly higher 74% yield
in 10a and 10a′ was obtained, yet with poor 48:52
regioselectivity (Table 1, entry 4). Note that in all cases similar
results were obtained upon quenching with aqueous HCl or
MeOH.
The positive results observed with Zn-9a generated from Li-
9a by the addition of 1 equiv of ZnBr2 followed by 2 equiv of
nBuLi or by the addition of preformed dibutylzinc were
attributed to the presence of 2 equiv of Lewis acidic LiBr that
could facilitate the epoxide ring opening. Consistent with this
hypothesis, the addition of HMPA (hexamethylphosphoric
triamide), known to be able to coordinate lithium cations,14
prevented the reaction with preformed nBu2Zn·2LiBr even at
20 °C (Table 1, entries 5−7). In contrast, when the reaction
was run with a salt-free commercial dibutylzinc solution and
adding 2 equiv of LiBr, no reaction was observed at −20 °C
(Table 1, entry 8). We attributed this failure to the low
solubility of this salt in the reaction medium as a turbid mixture
was obtained. Strikingly, when using MgBr2, assumed to be a
stronger Lewis acid than LiBr, the reaction did not occur below
0 °C, and only degradation of the substrate was noted at 20 °C
(Table 1, entries 9−11). Similarly, in the presence of only 1
equiv of LiBr, no reaction occurred at −20 °C, and
decomposition was observed above 0 °C (Table 1, entry 12).
All of these results indicated that the formation of
allenylzincs from acetylenic epoxides by three-carbon homo-
logation of diorganozincs was possible, provided it was
conducted in the presence of 2 equiv of LiBr, even though
the exact role of this salt was not clear.
Scope of the Three-Carbon Homologation. The scope
of the three-carbon homologation was next investigated under
the optimized conditions. To this end, various acetylenic
epoxides 9 were subjected to the reaction with preformed
dibutylzinc (nBu2Zn·2LiBr) at −20 °C for 1.5 h prior to
hydrolysis with aqueous HCl (Scheme 8). In all cases, mixtures
of the allenic and homopropargylic alcohols 10 and 10′,
respectively, were obtained. Although the combined isolated
yield was always good, the nature of the starting acetylenic
epoxide 9 highly impacted both the sense and the level of the
regioselectivity (Table 2). Moreover, in all cases, the
envisioned reinvestigating this reaction, and we report herein
our recent results in this field (Scheme 5).
RESULTS AND DISCUSSION
■
Preliminary Study. In order to circumvent the competitive
direct SN2′ mechanism observed by Marshall, we envisioned
generating the alkynylogous zinco-carbenoid by deprotonation
of the epoxide at the acetylenic terminus followed by
transmetalation with a diorganozinc. Our study was initially
conducted with acetylenic epoxide 9a prepared from cyclo-
hexanecarboxaldehyde using a known methodology (Scheme
6).11
When using a slight excess of nBuLi, the deprotonation was
complete within 10 min at −80 °C in THF. Deuterated epoxide
D-9a with >95% D-content was indeed quantitatively formed
upon addition of D2O. Note that the control of the amount of
nBuLi used is crucial to avoid α-deprotronation of the epoxide,
followed by 1,2-H shift rearrangement and the formation of the
corresponding allenic ketone.12
The anticipated formation of allenic alcohol 10a from lithium
dibutylzincate Zn-9a by reacting Li-9a with various zinc species
and then carrying out an acidic hydrolysis was examined
(Scheme 6). Unexpectedly, when a commercially available salt-
free solution of dibutylzinc was used, no reaction was observed
at all within 1 h at 20 °C, and epoxide 9a was quantitatively
recovered upon hydrolysis (Table 1, entry 1).
In contrast, the successive addition of 1 equiv of ZnBr2 and 2
equiv of nBuLi led, within 0.5 h at 20 °C, to a mixture of
inseparable allenic and homopropargylic alcohols, 10a and
10a′, respectively, upon hydrolysis, albeit in a modest 39%
combined yield and with no regioselectivity (Table 1, entry 2).
The regioselectivity observed here contrasts with the study of
Marshall in which only the allenic alcohol was obtained
(Scheme 4).9 This difference could be attributed to the
metallotropic equilibrium totally shifted toward allenylzinc 7 in
Scheme 4. Formation of an Allenylzinc from an Acetylenic Epoxide
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Scheme 5. Our Work
Scheme 6. Optimization of the Three-Carbon Homologation
Scheme 7. Origin of the Regioselectivity
diastereomeric ratio of allenic alcohols 12a−14a could not be
determined.
Interestingly, the dimethylphenylsilyl group could also be
transferred efficiently using bis(dimethylphenylsilyl)zinc
(Scheme 10), preformed from the parent silyllithium species15
(see the Experimental Section for details).
diastereomeric ratio of allenic alcohols 10 could not be
determined.
The three-carbon homologation of various dialkylzincs was
next examined through their reaction with acetylenic epoxide
9a (Scheme 9). These dialkylzincs were preformed as before by
the reaction of 1 equiv of ZnBr2 with 2 equiv of of the
corresponding alkyllithiums (see the Experimental Section for
details).
Except in the case of lithium dimethyzincate (Table 3, entry
1), high combined yields of allenic alcohols 12a−14a and
homopropargylic alcohols 12a′−14a′ were attained, albeit with
moderate selectivities (Table 3, entries 2 and 3). As before, the
The best yields were obtained when the rearrangement was
carried out for 2 h at −20 °C followed by an additional stirring
of 45 min at 0 °C prior to quenching with MeOH. To our
delight, the transfer of the silyl group occurred with high
regioselectivity, leading to 4-silylated homopropargylic alcohols
15′ as unique or major regioisomers (Table 4).
The corresponding allenic alcohols 15 could only be
detected as minor isomers with acetylenic epoxides 9b and 9i
Table 1. Optimization of the Three-Carbon Homologation (Scheme 6)
a
b
c
entry
zinc source
T (°C)
t (h)
10a:10a′ ratio
yield (%)
d
e
1
2
salt-free nBu2Zn
20
20
1
0
ZnBr2 then 2 equiv of nBuLi
ZnBr2 then 2 equiv of nBuLi
0.5
1.5
1.5
1.5
1
50:50
50:50
48:52
39
3
−20
−20
−20
0
40
f
4
nBu2Zn·2LiBr
74
f
5
nBu2Zn·2LiBr + HMPA
nBu2Zn·2LiBr + HMPA
nBu2Zn·2LiBr + HMPA
salt-free nBu2Zn + 2 equiv of LiBr
(0)
(0)
f
6
f
e
7
20
8
0
d
e
8
−20
−20
0
1
0
g
e
9
nBu2Zn·2MgBr2
nBu2Zn·2MgBr2
nBu2Zn·2MgBr2
2
0
g
e
10
11
12
2
0
g
20
2
decomposition
(0)
h
nBu2Zn·LiBr·MgBr2
−20
1
a
b
See the Experimental Section for the preparation of the zinc species. Regioselectivity determined by 1H NMR analysis at 400 MHz of the crude
c
1
reaction mixture. Combined isolated yield in 10a and 10a′. In parentheses is the conversion rate as measured by H NMR at 400 MHz.
d
e
f
Commercial 1 M solution in heptane. Epoxide 9a was quantitatively recovered. Preformed dibutylzinc: freshly prepared by the reaction of nBuLi
g
(2 equiv) with ZnBr2 (1 equiv) in THF from −80 to 0 °C. Preformed dibutylzinc: freshly prepared by the reaction of nBuMgBr (2 equiv) with
h
ZnBr2 (1 equiv) in THF from −80 to 0 °C. Preformed dibutylzinc: freshly prepared by the reaction of nBuMgBr (1 equiv) and nBuLi (1 equiv)
with ZnBr2 (1 equiv) in THF from −80 to 0 °C.
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Scheme 8. Three-Carbon Homologation of nBu2Zn·2LiBr with Epoxides 9
Table 2. Three-Carbon Homologation of nBu2Zn·2LiBr with Epoxides 9 (Scheme 8)
a
b
entry
R1
R2
epoxide
10:10′ ratio
yield (%)
1
2
3
4
5
Ph(CH2)2
Et2CH
tBu
H
H
H
H
Ph
9b (dr = 81:19)
9c (dr = 94:06)
9d (dr > 98:02)
9e (dr = 62:38)
9f
10b:10b′ = 58:42
10c:10c′ = 69:31
10d:10d′ = 83:17
10e:10e′ = 58:42
10f:10f′ = 13:87
70
68
72
57
62
c
Ph
d
Ph
a
b
1
Regioselectivity determined by H NMR analysis at 400 MHz of the crude reaction mixture. Combined isolated yield in 10 and 10′. The same
regioselectivity as in the crude material was observed. Conversion rate of 94%. Conversion rate of 89%. The reaction was carried out for 4 h at 0
c
d
°C then 1.5 h at 20 °C.
Scheme 9. Three-Carbon Homologation of R2Zn·2LiBr
the epoxide and/or of the group transferred. The exact reason
why the regioselectivity varies in such a way is unknown, even
through it is undoubtedly related to the metallotropic
allenylzinc/propargylzinc equilibrium.
Table 3. Three-Carbon Homologation of R2Zn·2LiBr
(Scheme 9)
a
b
entry
R
regioselectivity
yield (%)
28
1
2
3
4
Me
Et
12a:12a′ = 76:24
13a:13a′ = 68:32
14a:14a′ = 65:35
Stereoselective Access to 2-Alkynyl-1,3-diols. The
mixture of allenylzinc 11 and propargylzinc 11′, obtained
from acetylenic epoxide 9a (see Scheme 7), was first reacted
with cyclohexanecarboxaldehyde. Within 1 h at −20 °C, upon
hydrolysis, inseparable diastereomeric 2-alkynyl-1,3-diols16,17
16 and 17 were isolated in good yield with a complete control
of the regioselectivity (the corresponding allenic isomers not
being observed) and with a ratio of 85:15 in favor of 16
(Scheme 11). The exclusive formation of homopropargylic
diols was rationalized by the reactivity of 11 being greater with
carbonyl derivatives than that of 11′ through an SE2′ process.
Everything thus happened as if 11 were the only existing
metallotropic form in the medium.18
75
85
tBu
Ph
decomposition
a
1
Regioselectivity determined by H NMR analysis at 400 MHz of the
b
crude reaction mixture. Combined isolated yield in 12a−14a and
12a′−14a′. The same regioselectivity as in the crude material was
observed.
bearing a primary alkyl substituent (Table 4, entries 2 and 3)
and with aromatic epoxide 9e (Table 4, entry 6). Their
configuration could not be determined. Intriguingly, only
decomposition was observed in the case of alkenyl epoxide 9h
under the same conditions (Table 4, entry 9). The reason why
9h behaves differently from the others remains unexplained
even though the vinylogous nature of the epoxide, prone to
substitution giving multiple of products, could be invoked.
Interestingly, trisubstituted epoxides 9f and 9g led to the
corresponding quaternary homopropargylic alcohols in good
yields as unique regioisomers (Table 4, entries 7 and 8).
Diverse alkyl groups as well as the dimethylphenylsilyl group
could thus be transferred affording the corresponding allenic
and/or homopropargylic alcohols through ring opening of the
epoxide following an SN2′ process. In most cases, yields are
good while the regioselectivity highly depends on the nature of
Stereochemical assignment was achieved by NMR studies.
The major diastereomer 16 was first shown to be a symmetrical
1
1,3-diol by H NMR analysis, showing that hydrogens H1 and
H3 are identical and appear as a unique doublet of doublet at
3.37 ppm (Scheme 11). Similarly, the minor diastereomer 17
1
could be determined to be unsymmetrical by its H NMR
analysis, showing that H1 and H3 are different.
The relative configuration of 16 was next deduced from its
quantitative transformation into dioxolane 18 in which coupling
constants of 2.2 Hz were measured between H2 and H1 as well
as H3 (Scheme 12). These are typical of equatorial−equatorial
and/or axial−equatorial interactions meaning that the
Scheme 10. Three-Carbon Homologation of (PhMe2Si)2Zn·2LiBr
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Table 4. Three-Carbon Homologation of (PhMe2Si)2Zn·2LiBr (Scheme 10)
a
b
entry
R1
R2
epoxide 9
15:15′ ratio
<02:98
17:83
yield (%)
72
1
2
3
4
5
6
7
8
9
cHex
nBu
H
9a (dr = 89:11)
9i (dr = 80:20)
9b (dr = 81:19)
9c (dr = 94:06)
9d (dr > 98:02)
9e (dr = 62:38)
9f
H
64
65
72
79
86
72
76
Ph(CH2)2
Et2CH
tBu
H
07:93
H
<02:98
<02:98
16:84
H
Ph
H
Ph
Ph
nPent
H
<02:98
<02:98
nPent
9g
(E)-PhCHCH2
9h (dr > 98:02)
decomposition
a
b
1
Regioselectivity determined by H NMR analysis at 400 MHz of the crude reaction mixture. Combined isolated yield in 15 and 15′. The same
regioselectivity as in the crude material was observed.
Scheme 11. Access to 2-Alkynyl-1,3-diols
(1R*,2r*,3S*) stereochemistry could be unambiguously
attributed to 16.
Scheme 13. Possible Transition State Models
Scheme 12. Determination of the Configuration of 16
These results suggest that 16 arises only from allenylzinc
(aR)-11 while the formation of 17 can be formed either from
(aR)-11 or (aS)-11 (Scheme 13). In order to gain insight into
the stereoselectivity of the formation of 11 and its subsequent
reaction with aldehydes, we carried out a series of reactions
with epoxide 9a and varying the trapping conditions (Scheme
14).
Interestingly, when cyclohexanecarboxaldehyde was rapidly
added dropwise at −20 °C only 5 min following the addition of
dibutylzinc to Li-9a, adducts 16 and 17 were obtained in low
35% yield and with a 16:17 ratio of 57:43. The
diastereoselectivity was considerably lower than that observed
when adding the aldehyde 90 min after dibutylzinc (Table 5,
entry 1 vs 2). Moreover, the sense of the diastereoselectivity
could be reversed when the aldehyde was rapidly and
The preferred formation of diastereomer 16 could be
rationalized by the favored Chodkiewicz−Yamamoto-type19
transition state model M1 in which allenylzinc (aR)-11 reacts
with the aldehyde (Scheme 13). Analogously, 17 could be arise
from the disfavored competitive more energetic chelate models
M2 or M3. Transition state model M1 is favored relative to M2
due to less steric interactions between the allenylzinc and the
aldehyde. The preference for M1 versus M3 was explained by
the “inside alkoxy effect” that enhances the nucleophilicity of
the allenylzinc (Houk-type model).20,21
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Scheme 14. Study of the Configurational Stability of 11
means that the equilibration of (aS)-11 is faster than its
reaction with the aldehyde at this temperature. Indeed, in the
case of a slow equilibration, an increased diastereoselectivity
would have been observed by giving more time to (aS)-11 to
isomerize into (aR)-11. On the other hand, the result obtained
at −60 °C could be interpreted by a slow isomerization of (aS)-
11 relative to the rate of its reaction with the aldehyde.
However, we cannot currently provide an explanation why
(aS)-11 rapidly epimerizes into (aR)-11, and to why the
equilibrium is shifted toward (aR)-11.18,22 Nevertheless, a
greater reactivity of (aR)-11 (through M1) than that of (aS)-11
(through M3) might be invoked (see Scheme 13).
We next studied the scope of this new diastereoselective
access to 2-alkynyl-1,3-diols by trapping allenylzincs (aR)-11,
20, and 21, generated from the appropriate acetylenic epoxides
9 and dialkylzincs R2Zn·2LiBr, with carbonyl derivatives
(Scheme 15).
Table 5. Study of the Configurational Stability of 11
(Scheme 14)
a
b
c
d
entry T (°C) t (min)
addition rate (min)
16:17
yield (%)
1
2
3
4
−20
−20
−60
−20
90
5
0.33
0.33
0.33
210
85:15
57:43
27:73
84:16
66
35
e
f
0
7
90
79
a
Time of stirring at the appropriate temperature after completion of
the addition of dibutylzinc to Li-9a and before the addition of
b
cyclohexanecarboxaldehyde. Addition rate of cyclohexanecarbox-
c
aldehyde to the reaction mixture. Ratio determined by 1H NMR
d
analysis at 400 MHz of the crude reaction mixture. Isolated combined
e
yield in 16 and 17. Cyclohexanecarboxaldehyde was added
f
immediately after preformed dibutylzinc. The major product resulted
from the addition of cyclohexanecarboxaldehyde at the acetylenic
terminus of 9a.
When allenylzinc 11 was trapped with propanal and
pivaldehyde, the corresponding 2-alkynyl-1,3-diols were
obtained with a complete regioselectivity in good yields and
diastereoselectivities ≥85:15 (Table 6, entries 1 and 2). The
relative configuration of major diastereomers 22 and 23 was
inferred by analogy with that of 16 and can be explained on the
basis of the favored transition state model M1 (Scheme 13).
The stereochemistry of minor isomers 27 and 28 could not be
assigned. It is, however, worth noting that the bulkiness of the
R substituent of the aldehyde has no influence on the
diastereoselectivity, thereby suggesting that these adducts are
obtained via model M3 rather than M2 (Scheme 13). Hence,
their relative configuration could be assigned.
immediately added after dibutylzinc at −60 °C. In this case, the
expected 16 and 17 adducts were obtained with a 16:17 ratio of
27:73 in very poor 7% yield, the main product resulting from
the direct nucleophilic attack of the zincate to the aldehyde
(Table 5, entry 3).
These results were in accord with a mechanistic picture
involving the initial formation of (aS)-11, via the classical anti-
SN2′ migration of a butyl substituent from zincate Zn-9a, and
isomerization to give (aR)-11. In this context, a last experiment
was carried out by slowly adding the aldehyde at −20 °C 90
min after dibutylzinc. In this case, both the yield and the
diastereoselectivity were close to those obtained when the
aldehyde was rapidly added under the same conditions (Table
5, entry 1 vs 4). This last experiment suggested that the
Curtin−Hammet principle applies at −20 °C and thereby
When the 1,3-diol preparation was carried out with
tBu2Zn·2LiCl and 9a, a reversal of the diastereoselectivity was
observed, the generated allenylzinc 20 leading to major isomer
Scheme 15. Diastereoselective Preparation of 2-Alkynyl-1,3-diols
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Table 6. Diastereoselective Preparation of 2-Alkynyl-1,3-diols (Scheme 15)
a
entry
R1 (epoxide)
allenylzinc
R2
nBu
R3
Et
R4
stereoselectivity
yield (%)
b
b
b
d
d
1
2
3
4
5
6
cHex (9a)
cHex (9a)
cHex (9a)
cHex (9a)
cHex (cis-9a)
Et2CH (9c)
11
11
20
11
11
21
H
22:27 = 87:13
78
59
88
77
59
nBu
tBu
cHex
Me
H
23:28 = 85:15
tBu
H
24:29 = 36:64
nBu
Me
Me
Me
c
e
f
nBu
Me
dg
,
SiMe2Ph
Me
42
a
b
Stereoselectivity determined by 1H NMR analysis at 400 MHz of the crude reaction mixture. Combined isolated yield. The same regioselectivity as
c
d
e
in the crude material was observed. Only compound 25 was obtained with 94:06 regioselectivity. Yield in purified major products. Only
compound 25 was obtained with 93:07 regioselectivity. Only compound 26 was obtained with 88:12 regioselectivity. Reaction carried out for 2.5 h
at −40 °C.
f
g
Figure 1. ORTEP drawing of 24 (hydrogens have been omitted for clarity).
Scheme 16. Diastereoconvergent Generation of Allenylzinc (aR)-11
29, albeit with a modest selectivity of 64:36 (Table 6, entry 3).
The stereochemistry of the minor isomer 24 could be
unambiguously assigned from crystal X-ray analysis (Figure
1).23 This reversal of the stereoselectivity remains puzzling.
In addition to aldehydes, trapping of allenylzincs 11 and 21
could be efficiently performed with acetone, thus leading to the
corresponding 2-alkynyl-1,3-diols in good yields with good
regio- and stereoselectivities (Table 6, entries 4−6). Interest-
ingly, diastereoconvergent results were obtained from isomeric
acetylenic epoxides 9a and cis-9a that gave exclusively the same
adduct 25 (Table 6, entries 4 and 5). Most likely, cis-Zn-9a
undergoes an anti-SN2′ migration of the butyl group, leading
directly to allenylzinc intermediate (aR)-11 (Scheme 16).
zincates that undergo migration of an alkyl or silyl group. In the
case of (2R,3R)-2-alkyl-3-ethynyl epoxides, the migration
occurs by an anti-SN2′ pathway, leading to (aS) allenylzinc
intermediates. The latter rapidly epimerize and afford the
corresponding (aR) allenylzincs, which are the reactive species.
In the case of the (2R,3S) diastereomeric epoxides, the same
(aR) allenylzincs are directly formed following the same anti-
SN2′ pathway. When dialkylzincs are used in the trans-
metalation step, mixtures of homopropargylic and allenic
alcohols are obtained with modest regioselectivites upon
hydrolysis. Conversely, the reactions involving bis(dimethyl-
phenylsilyl)zinc lead to the corresponding homopropargylic
alcohols in high yields and excellent regioselectivity. Trapping
of allenylzinc intermediates with carbonyl derivatives has been
shown to give stereoselectively 2-alkynyl-1,3-diols. The
extension of this methodology to acetylenic aziridines is
under investigation in our group and will be reported in due
course.
CONCLUSION
■
Allenylzinc formation from acetylenic epoxides has been
developed through deprotonation at the acetylenic position
and subsequent transmetalation with diorganozincs, leading to
140
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Article
1972 cm−1; HMRS (ESI) m/z calcd for C16H23O+ 231.1743 [M + H+],
found 231.1750.
EXPERIMENTAL SECTION
■
General Methods. Experiments involving organometallics were
carried out in dried glassware under a positive pressure of dry nitrogen.
Liquid nitrogen was used as a cryoscopic fluid. A three-necked, round-
bottomed flask equipped with an internal thermometer, a septum cap,
and a nitrogen inlet was used. Anhydrous THF and Et2O were
obtained by distillation over sodium benzophenone ketyl. Zinc
bromide was purchased from Aldrich, melted under argon, and,
immediately after cooling to room temperature, dissolved in
anhydrous THF or Et2O. Commercial solutions of nBuLi and tBuLi
were titrated with sBuOH (1 M solution in toluene) in the presence of
2,2′-dichinolyl or with Suffert’s reagent.24 All other reagents and
solvents were of commercial quality and were used without further
purification. Flash chromatographies were carried out over silica gel 60
(230−400 mesh). IR spectra were recorded with an ATR diamant
spectrophotometer. Chemical shifts are reported in δ units relative to
Mixture of ( )-3-Ethylundeca-5,6-dien-4-ol (10c) and ( )-3-
Ethylundec-6-yn-4-ol (10c′): Colorless oil (66 mg, 68%, 10c:10c′ =
69:31, indeterminable dr for 10c) obtained according to SP1 from
1
epoxide 9c (68 mg, 0.50 mmol) and nBu2Zn·2LiBr; H NMR (400
MHz, CDCl3) δ 5.34−5.26 (m, 1 H 10c), 5.26−5.15 (m, 1 H 10c),
4.21−4.09 (m, 1 H 10c), 3.67 (m, 1 H 10c′), 2.38 (ABX system, J =
16.5, 4.6, 2.4 Hz, 1 H 10c′), 2.31 (ABX system, J = 16.5, 7.9, 2.4 Hz, 1
H 10c′), 2.20−2.12 (m, 1 H 10c), 2.08−1.97 (m, 1 H), 1.92−1.88 (m,
1 H 10c′), 1.62−1.52 (m, 1 H), 1.52−1.18 (m, 9 H), 0.96−0.77 (m, 9
H); 13C NMR (100 MHz, CDCl3) δ 202.7 (10c), 94.7 and 94.5 (two
isomers of 10c), 94.24 and 94.17 (two isomers of 10c), 83.3 (10c′),
76.7, 71.8, 71.6, 71.2, 47.3, 45.5, 31.5, 31.2, 28.7, 25.2, 22.3, 22.1, 22.0,
21.8, 21.6, 21.1, 18.6, 14.0, 13.7, 11.9, 11.8, 11.7, 11.5; IR (neat) ν
3328, 2924, 2172 (10c′), 1961 (10c) cm−1; HMRS (ESI) m/z calcd
for C13H25O+ 197.1900 [M + H+], found 197.1896.
Mixture of ( )-2,2-Dimethyldeca-4,5-dien-3-ol (10d) and
( )-2,2-Dimethyldec-5-yn-3-ol (10d′): Colorless yellow oil (70
mg, 72%, 10d:10d′ = 83:17, indeterminable dr for 10d) obtained
according to SP1 from epoxide 9d (65 mg, 0.53 mmol) and
nBu2Zn·2LiBr. Further purification by flash chromatography afforded
analytically pure products. Data for 10d: 1H NMR (400 MHz, CDCl3)
δ 5.36−5.30 (m, 1 H), 5.29−5.25 (m, 1 H), 3.76 (dd, J = 5.7, 2.8 Hz,
1H), 2.06−2.00 (m, 2 H), 1.67 (br s, 1 H), 1.43−1.28 (m, 4 H), 0.90
(s, 9 H), 0.89 (t, J = 7.2 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ
202.7 and 202.3 (two isomers), 94.8 and 94.1 (two isomers), 92.9 and
92.6 (two isomers), 77.8, 35.5, and 35.4 (two isomers), 28.54 and
28.46 (two isomers), 25.47 and 25.45 (two isomers), 21.5, 13.9. Data
for 10d′: 1H NMR (400 MHz, CDCl3) δ 3.36 (dd, J = 10.0, 2.8 Hz, 1
H), 2.42−2.35 (m, 1 H), 2.26−2.10 (m, 3 H), 2.06−1.79 (m, 1 H),
1.52−1.11 (m, 4 H), 0.97−0.80 (m, 12 H); 13C NMR (100 MHz,
CDCl3) δ 82.3, 77.7, 77.4, 34.5, 31.2, 25.8, 23.0, 18.6, 13.7; IR (neat) ν
3419, 2955, 2930, 2870, 1962 cm−1; HMRS (ESI) m/z calcd for
C12H23O+ 183.1743 [M + H+], found 183.1746.
Mixture of ( )-1-Phenylocta-2,3-dien-1-ol (10e) and ( )-1-
Phenyloct-3-yn-1-ol (10e′): Pale yellow oil (58 mg, 57%, 10e:10e′
= 58:42) obtained according to SP1 from epoxide 9e (72 mg, 0.50
mmol) and nBu2Zn·2LiBr; 1H NMR (400 MHz, CDCl3) δ 7.44−7.29
(m, 5 H), 5.45−5.35 (m, 2 H 10e), 5.26−5.22 (m, 1 H 10e), 4.82 (dd,
J = 7.5, 5.2 Hz, 1 H 10e′), 2.62−2.47 (m, 3 H 10e′), 2.28−2.17 (m, 2
H 10e and 1 H 10e′), 2.17−2.00 (m, 1 H), 1.51−1.29 (m, 4 H), 0.90
(m, 3 H); 13C NMR (100 MHz, CDCl3) δ 202.3 and 202.0 (two
isomers of 10e), 143.2, 143.1, 142.8, 128.5, 128.4, 127.8, 127.72,
127.67, 126.2, 126.1, 125.8, 96.2 and 96.1 (two isomers of 10e), 95.4,
and 95.1 (two isomers of 10e), 83.6 (10e′), 77.3, 76.0, 72.7, 72.4, 72.2,
31.3, 31.2, 31.0, 30.1, 28.5, 22.2, 22.0, 18.5, 14.0, 13.7; IR (neat) ν
3419, 2955, 2930, 2870, 1962 cm−1; HMRS (ESI) m/z calcd for
C14H19O+ 203.1430 [M + H+], found 203.1434.
1
an internal standard of residual chloroform (δ = 7.27 ppm for H
NMR and δ = 77.1 ppm for 13C NMR). HRMS were obtained using a
Q-TOF instrument equipped with ESI source.
Standard Procedure for the Three-Carbon Homologation of
Dialkylzincs (SP1). Under a nitrogen atmosphere, to ZnBr2 (1.00 M
solution in THF, 0.55 mL, 0.55 mmol) in THF (0.5 mL) was added
RLi (1.1 mmol) at −80 °C. After 5 min of stirring at −80 °C, the
mixture was allowed to warm to 0 °C. The resulting solution of
dialkylzinc (R2Zn·2LiBr) was immediately used in the reaction with
lithiated epoxides.
Under a nitrogen atmosphere, at −80 °C to a solution of epoxide
(0.50 mmol) in THF (4 mL) was added dropwise nBuLi (2.20 M in
hexanes, 0.25 mL, 0.55 mmol). After 10 min of stirring at −80 °C, the
mixture was allowed to warm to −60 °C and the above prepared
dialkylzinc was added. The resulting mixture was warmed to −20 °C
then stirred for 1.5 h at this temperature. The reaction was quenched
with a 0.5 M aqueous HCl solution (10 mL), and Et2O (10 mL) was
added. The layers were separated, and the aqueous one was extracted
with Et2O (2 × 10 mL). The combined organic layers were washed
with water (15 mL) and brine (15 mL) and dried over anhydrous
MgSO4. Removal of the solvent in vacuum and purification by flash
chromatography (10% Et2O/pentane) afforded mixtures of alcohols
10, 12−14 and 10′, 12′−14′ (Tables 2 and 3).
Mixture of ( )-1-Cyclohexylocta-2,3-dien-1-ol (10a) and
( )-1-Cyclohexyloct-3-yn-1-ol and (10a′): Colorless yellow oil
(78 mg, 74%, 10a:10a′ = 48:52, indeterminable dr for 10a) obtained
according to SP1 from epoxide 9a (76 mg, 0.50 mmol) and
1
nBu2Zn·2LiBr; H NMR (CDCl3, 400 MHz) δ 5.33−5.27 (m, 1 H
10a), 5.27−5.14 (m, 1 H 10a), 3.89−3.85 (m, 1 H 10a), 3.41−3.38
(m, 1 H 10a′), 2.41 (ABX system, J = 16.5, 4.4, 2.4 Hz, 1 H 10a′), 2.29
(ABX system, J = 16.5, 7.6, 2.4 Hz, 1 H 10a′), 2.18−2.14 (m, 1 H),
2.0−1.93 (m, 1 H), 1.92−1.73 (m, 1 H), 1.72−1.57 (m, 5 H), 1.50−
1.39 (m, 5 H), 1.38−0.94 (m, 5 H), 0.93−0.87 (m, 3 H); 13C NMR
(CDCl3, 100 MHz) δ 202.7 and 202.3 (two isomers of 10a), 94.4 and
94.3 (two isomers of 10a), 83.3 (10a′), 76.5, 74.4, 74.1, 44.2, 44.1,
42.76, 31.4, 31.2, 29.1, 28.9, 28.62, 28.60, 28.5, 28.4, 28.3, 26.3, 26.25,
26.23, 26.17, 26.15, 25.1, 22.3, 22.2, 22.1, 18.6, 14.0, 13.7; IR (neat) ν
3349, 2922, 2852, 1962 cm−1; HMRS (ESI) m/z calcd for C14H25O+
209.1900 [M + H+], found 209.1896.
Mixture of ( )-1,1-Diphenylocta-2,3-dien-1-ol (10f) and
( )-1,1-Diphenyloct-3-yn-1-ol (10f′): Pale yellow oil (81 mg,
62%, 10f:10f′ = 13:87) obtained according to SP1 from epoxide 9f
(65 mg, 0.53 mmol) and nBu2Zn·2LiBr. Further purification by flash
1
chromatography afforded analytically pure products. Data for 10f: H
NMR (400 MHz, CDCl3) δ 7.47−7.44 (m, 4 H), 7.34−7.30 (m, 4 H),
7.27−7.23 (m, 2 H), 5.90 (dt, J = 6.2, 3.0 Hz, 1 H), 5.41 (q, J = 6.2 Hz,
1 H), 2.67 (s, 1 H), 2.05−1.98 (m, 2 H), 1.27−1.21 (m, 2 H), 0.86 (t,
J = 7.1 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 200.8, 146.5, 128.1,
127.3, 126.9, 126.8, 101.0, 97.5, 77.3, 31.3, 28.6, 22.3, 14.0. Data for
10f′: 1H NMR (400 MHz, CDCl3) δ 7.45−7.42 (m, 4 H), 7.34−7.30
(m, 4 H), 7.26−7.20 (m, 2 H), 3.12 (t, J = 2.3 Hz, 2 H), 3.08 (br s, 1
H), 2.09 (tt, J = 7.0, 2.3 Hz, 2 H), 1.39−1.32 (m, 2 H), 1.28−1.19 (m,
2 H), 0.82 (t, J = 7.3 Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 145.9,
128.2, 127.2, 126.3, 85.2, 77.2, 75.8, 33.9, 30.9, 21.8, 18.5, 13.7; HMRS
(ESI) m/z calcd for C20H23O+ 279.1743 [M + H+], found 279.1747.
Mixture of ( )-1-Cyclohexylpenta-2,3-dien-1-ol (12a) and
( )-1-Cyclohexylpent-3-yn-1-ol (12a′): Colorless oil (23 mg, 28%,
12a:12a′ = 76:24, indetermibable dr for 12a) obtained according SP1
Mixture of ( )-1-Phenyldeca-4,5-dien-3-ol (10b) and ( )-1-
Phenyldec-3-yn-1-ol (10b′): Colorless oil (81 mg, 70%, 10b:10b′ =
58:42, indeterminable dr for 10b) obtained according to SP1 from
1
epoxide 9b (87 mg, 0.51 mmol) and nBu2Zn·2LiBr; H NMR (400
MHz, CDCl3) δ 7.31−7.26 (m, 2 H), 7.23−7.17 (m, 3 H), 5.36−5.29
(m, 1 H 10b), 5.29−5.23 (m, 1 H 10b), 4.19−4.13 (m, 1 H 10b),
3.75−3.68 (m, 1 H 10b′), 2.84−2.65 (m, 2 H), 2.42 (ABX system, J =
16.5, 4.6, 2.3 Hz, 1 H 10b′), 2.31 (ABX system, J = 16.5, 6.7, 2.3 Hz, 1
H 10b′), 2.19−2.16 (m, 1 H), 2.07−1.92 (m, 1 H), 1.91−1.63 (m, 3
H), 1.51−1.21 (m, 4 H), 0.93−0.89 (m, 3 H); 13C NMR (100 MHz,
CDCl3) δ 202.3 and 202.2 (two isomers of 10b) 142.11, 142.07, 142.0,
128.59, 128.57, 128.5, 126.0, 125.9, 95.7, and 95.6 (two isomers of
10b), 94.8 and 94.6 (two isomers of 10b), 83.6 (10b′), 75.9, 69.54,
69.51, 69.2, 39.23, 39.21, 38.0, 32.1, 31.9, 31.8, 31.38, 31.36, 31.2,
28.60, 28.58, 28.0, 22.3, 22.1, 18.5, 14.0, 13.7; IR (neat) ν 3340, 2925,
1
from epoxide 9a (75 mg, 0.50 mmol) and Me2Zn·2LiBr; H NMR
(400 MHz, CDCl3) δ 5.32−5.22 (m, 1 H 12a), 5.22−5.16 (m, 1 H
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Article
12a), 3.92−3.85 (m, 1 H 12a) 3.47−3.39 (m, 1 H 12a), 2.45−2.38
(m, 1 H, 12a), 2.33−2.25 (m, 1 H 12a), 2.00−1.57 (m, 8 H), 1.51−
1.37 (m, 1 H), 1.37−0.92 (m, 6 H); 13C NMR (100 MHz, CDCl3) δ
203.5 and 203.2 (two isomers of 12a), 93.7 and 93.6 (two isomers of
12a), 88.8 and 88.4 (two isomers of 12a), 78.4 (12a′), 75.7, 75.6, 74.3,
74.1, 44.2, 44.1, 42.6, 29.1, 28.8, 28.4, 28.3, 26.6, 26.5, 26.2, 25.0,
14.52, 14.46, 3.7; IR (neat) ν 3395, 2962, 1961 cm−1; HMRS (ESI) m/
z calcd for C11H19O+ 167.1430 [M + H+], found 167.1427.
Mixture of ( )-1-Cyclohexylhex-2,3-dien-1-ol (13a) and
( )-1-Cyclohexylhex-3-yn-1-ol (13a′): Colorless oil (60 mg, 75%,
13a:13a′ = 68:32, indeterminable dr for 13a) obtained according SP1
from epoxide 9a (75 mg, 0.50 mmol) and Et2Zn·2LiBr; 1H NMR (400
MHz, CDCl3) δ 5.42−5.33 (m, 1 H 13a), 5.28−5.19 (m, 1 H 13a),
3.88−3.79 (m, 1 H 13a), 3.47−3.38 (m, 1 H 13a′), 2.45−2.37 (m, 1 H
13a′), 2.28 (ddt, J = 16.5, 7.8, 2.3 Hz, 1 H 13a′), 2.20−2.17 (m 2 H
13a′), 2.07−1.99 (m, 1 H 13a and 2 H 13a), 1.99−1.78 (m, 1 H),
1.78−1.64 (m, 5 H), 1.46−1.37 (m, 1 H), 1.29−0.95 (m, 4 H), 1.15−
0.98 (m, 3 H); 13C NMR (100 MHz, CDCl3) δ 202.3 and 201.8 (two
isomers of 13a), 96.3 and 95.6 (two isomers of 13a), 95.1 and 94.8
(two isomers of 13a), 84.6 (13a′), 77.3, 75.9, 74.7, 74.3, 74.0, 44.3,
44.2, 44.1, 42.6, 28.8, 28.2, 26.6, 26.5, 26.24, 26.19, 26.1, 22.0, 14.3,
13.5, 12.5; IR (neat) ν 3346, 2922, 1960 cm−1; HMRS (ESI) m/z
calcd for C12H21O+ 188.1587 [M + H+], found 188.1584.
Mixture of ( )-1-Cyclohexyl-5,5-dimethylhex-2,3-dien-1-ol
(14a) and ( )-1-Cyclohexyl-5,5-dimethylhex-3-yn-1-ol (14a′):
Colorless oil (41 mg, 85%, 14a:14a′ = 65:35 indeterminable dr for
14a) obtained according to SP1 from epoxide 9a (75 mg, 0.50 mmol)
and tBu2Zn·2LiBr; 1H NMR (400 MHz, CDCl3) δ 5.36−5.24 (m, 2 H
14a), 3.91−3.87 (m, 1 H 14a), 3.45−3.37 (m, 1 H 14a′), 2.40 (ABX
system, J = 16.4, 4.0 Hz, 1 H 14a′), 2.27 (ABX system, J = 16.4, 8.0
Hz, 1 H 14a′), 2.02 (br s, 1 H 14a′), 1.92−1.77 (m, 2 H 14a and 1 H
14a′), 1.77−1.65 (m, 5 H), 1.50−1.37 (m, 1 H), 1.37−1.09 (m, 6 H),
1.09−0.98 (m, 8 H); 13C NMR (100 MHz, CDCl3) δ 200.1 and 199.1
(two isomers of 14a), 106.9 and 105.8 (two isomers of 14a), 96.3 and
96.0 (two isomers of 14a), 92.1 (14a′), 77.3, 74.9, 74.8, 74.1, 73.9,
73.9, 44.3, 44.1, 42.7, 32.0,1, 31.97, 31.3, 30.3, 29.0, 28.94, 28.87, 28.6,
38.5, 28.4, 28.3, 27.5, 26.6, 26.3, 26.2, 26.12, 26.10, 25.0; IR (neat) ν
3395, 2960, 2925, 2853, 1961 cm−1; HMRS (ESI) m/z calcd for
C14H25O+ 209.1900 [M + H+], found 209.1903.
Standard Procedure for the Three-Carbon Homologation of
Bis(dimethylphenylsilyl)zinc (SP2). Li (50 mg, 7.23 mmol) was cut
into pieces and placed in a round-bottomed flask under an argon
atmosphere. Li was washed with pentane (2 × 3 mL), followed by
THF (2 × 3 mL), and then suspended into THF (3 mL).
Chlorotrimethylsilane (0.50 mL, 3.97 mmol) was added, and the
suspension was sonicated for 15 min. The solution was removed, and
activated Li was washed with THF (2 × 6 mL) and finally suspended
into THF (3 mL). The mixture was degassed at the sonicator for 3
min and then cooled to 0 °C. Dimethylphenyl chlorosilane (0.31 mL,
1.87 mmol) was added, and the mixture was sonicated for 2 h at 0 °C.
The deep red solution obtained was cooled to −60 °C, and ZnBr2
(1.00 M solution in THF, 0.75 mL, 0.75 mmol) was added. The
solution was stirred for 10 min at −20 °C to give a dark orange
solution of bis(dimethylphenylsilyl)zinc [(PhMe2Si)2Zn·2LiBr] ready
for use.
(
)-1-Cyclohexyl-4-[(dimethyl)phenylsilyl]but-3-yn-1-ol
(15a′): Colorless oil (103 mg, 72%) obtained according to SP2 from
1
epoxide 9a (75 mg, 0.50 mmol); H NMR (400 MHz, CDCl3) δ
7.70−7.60 (m, 2 H), 7.45−7.35 (m, 3 H), 3.53 (m, 1H), 2.56 (ABX
system, J = 16.9, 4.5 Hz, 1 H), 2.43 (ABX system, J = 16.9, 7.6 Hz, 1
H), 2.05−1.60 (m, 6 H), 1.57−1.40 (m, 1 H), 1.38−0.9 (m, 4 H), 0.42
(s, 6 H); 13C NMR (100 MHz, CDCl3) δ 137.3, 133.7, 129.5, 128.0,
105.9, 85.6, 74.0, 42.8, 29.1, 28.2, 26.5, 26.4, 26.3, 26.1, −0.6; IR
(neat) ν 3424, 3069, 2925, 2853, 2175 cm−1; HMRS (ESI) m/z calcd
for C18H26OSiNa+ 309.1645 [M + Na+], found 309.1649.
( )-6-(Dimethyl)phenylsilyl-1-phenylhex-5-yn-3-ol (15b′):
Colorless oil (100 mg, 65%, 15b:15b′ = 07:93, indeterminable dr
for 15b) obtained according to SP2 from epoxide 9b (88 mg, 0.50
mmol). For the mixture of 15b and 15b′: 1H NMR (400 MHz,
CDCl3) δ 7.72−7.61 (m, 2 H), 7.47−7.35 (m, 4 H), 7.35−7.26 (m, 4
H), 7.26−7.18 (m, 2 H), 5.32 (dd, J = 6.7, 2.3 Hz, 1 H 15b), 5.00 (app
t, J = 8.7, 1 H 15b), 4.25−4.15 (br s, 1 H 15b), 3.78 (app quint, J = 6.4
Hz, 1 H), 2.83−2.71 (m, 1 H, m), 2.69−2.64 (m, 1 H), 2.56 (ABX
system, J = 16.8, 5.2 Hz, 1 H), 2.49 (ABX system, J = 16.8, 6.6 Hz, 1
H), 2.10 (br s, 1 H), 1.95−1.86 (m, 2 H), 0.46 (s, 6 H), 0.45 (s, 6 H
15b); 13C NMR (100 MHz, CDCl3) δ 141.8 (15b), 137.3 (15b),
133.7, 133.2 (15b), 129.7 (15b′), 129.5, 128.5, 128.0, 126.0, 105.0,
85.9, 69.3, 37.9, 31.9, 29.2, 0.1, −0.6; IR (neat) ν 3337, 3025, 2955,
2174 (15b′), 1938 (15b) cm−1; HMRS (ESI) m/z calcd for
C20H24OSiNa+ 331.1489 [M + Na+], found 331.1494.
(
)-6-(Dimethyl)phenylsilyl-1-phenylhex-5-yn-3-ol (15c′):
Colorless oil (99 mg, 72%) obtained according to SP2 from epoxide
9c (69 mg, 0.50 mmol); H NMR (400 MHz, CDCl3) δ 7.65−7.62
1
(m, 2 H), 7.41−7.39 (m, 3 H), 3.80 (br s, 1 H), 2.54 (ABX system, J =
16.8, 4.7 Hz, 1 H), 2.48 (ABX system, J = 16.8, 7.5 Hz, 1 H), 1.51−
1.23 (m, 5 H), 0.93−0.89 (m, 6 H), 0.43 (s, 6 H); 13C NMR (100
MHz, CDCl3) δ 137.3, 133.7, 129.5, 129.4, 128.0, 106.0, 85.6, 83.5,
71.4, 47.5, 26.5, 21.9, 21.1, 11.6, −0.6; IR (neat) ν 3390, 3069, 2960,
2875, 2174 cm−1; HMRS (ESI) m/z calcd for C17H26OSiNa+ 297.1645
[M + Na+], found 297.1650.
(
)-2,2-Dimethyl-6-[(dimethyl)phenylsilyl]hex-5-yn-3-ol
(15d′): Colorless oil (102 mg, 79%) obtained according to SP2 from
1
epoxide 9d (62 mg, 0.50 mmol); H NMR (400 MHz, CDCl3) δ
7.68−7.62 (m 2 H), 7.44−7.35 (m, 3 H), 3.49 (dd, J = 9.9, 3.0 Hz, 1
H), 2.56 (ABX system, J = 16.8, 3.0 Hz, 1 H), 2.38 (ABX system, J =
16.8, 9.9 Hz, 1 H), 2.08 (br s, 1 H), 0.95 (s, 9 H), 0.44 (s, 6 H); 13C
NMR (100 MHz, CDCl3) δ 137.3, 133.7, 129.5, 128.0, 106.7, 85.6,
77.4, 34.7, 25.8, 24.4, −0.6; IR (neat) ν 3579, 3069, 2957, 2870, 2174
cm−1; HMRS (ESI) m/z calcd for C16H24OSiNa+ 283.1489 [M +
Na+], found 283.1496.
(
)-4-(Dimethyl)phenylsilyl-1-phenylhex-5-yn-3-ol (15e′):
Colorless oil (121 mg, 86%, 15e:15e′ = 16:84, indeterminable dr for
15e) obtained according to SP2 from epoxide 9e (72 mg, 0.50 mmol).
For the mixture of 15e and 15e′: H NMR (400 MHz, CDCl3) δ
7.62−7.57 (m, 4 H), 7.44−7.30 (m, 6 H), 5.33−5.28 (m, 1 H 15e),
5.26−5.17 (m, 1 H 15e), 4.90 (t, J = 6.2 Hz, 1 H), 2.74 (d, J = 6.2 Hz,
2 H), 2.43 (br s, 1 H), 0.41 (s, 9 H); 13C NMR (100 MHz, CDCl3) δ
142.6, 137.2, 133.8, 133.2, 129.8, 129.5, 128.6, 128.0, 125.9, 104.9,
86.1, 72.5, 31.3, 0.1 (15e), −0.7; IR (neat) ν 3320, 3068, 2958, 2176
cm−1; HMRS (ESI) m/z calcd for C18H20OSiNa+ 303.1176 [M +
Na+], found 303.1180.
1
Under a nitrogen atmosphere, at −80 °C to a solution of epoxide
(0.50 mmol) in THF (4 mL) was added dropwise nBuLi (2.20 M in
hexanes, 0.25 mL, 0.55 mmol). After 10 min of stirring at −80 °C, the
mixture was allowed to warm to −60 °C, stirred 20 min at this
temperature, and then canulated to the above prepared solution of
bis(dimethylphenylsilyl)zinc (0.75 mmol). The resulting mixture was
warmed to −20 °C and then stirred for 2 h at this temperature
followed by an additional stirring of 45 min at 0 °C. The reaction was
quenched with MeOH (10 mL), and Et2O (10 mL) was added. The
layers were separated, and the aqueous one was extracted with Et2O (2
× 10 mL). The combined organic layers were washed with water (15
mL) and brine (15 mL) and then dried over anhydrous MgSO4.
Removal of the solvent in vacuum and purification by flash
chromatography (40% CH2Cl2/cyclohexane) afforded homopropar-
gylic alcohols 15′ (Table 4).
(
)-6-(Dimethyl)phenylsilyl-1,1-diphenylhex-5-yn-3-ol
(15f′): Pale yellow oil (129 mg, 72%) obtained according to SP2 from
1
epoxide 9f (110 mg, 0.50 mmol); H NMR (400 MHz, CDCl3) δ
7.50−7.48 (m, 4 H, m), 7.40−7.26 (m, 11 H), 3.25 (s, 2 H), 2.98 (s, 1
H), 0.31 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ 145.6, 137.1, 133.7,
129.4, 128.3, 128.0, 127.4, 126.4, 104.8, 87.7, 35.3, −0.8; IR (neat) ν
3555, 3064, 2957, 2174 cm−1; HMRS (ESI) m/z calcd for
C24H24OSiNa+ 379.1489 [M + Na+], found 379.1495.
(
)-6-(Dimethyl)phenylsilyl-1,1-dipentylhex-5-yn-3-ol
(15g′): Pale yellow oil (131 mg, 76%) obtained according to SP2 from
1
epoxide 9g (104 mg, 0.50 mmol); H NMR (400 MHz, CDCl3) δ
7.63−7.61 (m, 2 H′), 738−7.33 (m, 3 H), 2.44 (s, 2 H), 1,68 (br s, 1
H), 1.61−1.52 (m, 4 H), 1.26−1.40 (m, 12 H), 0.90 (t, J = 7.0 Hz, 6
H), 0.40 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ 137.4, 133.7, 129.4,
142
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128.0, 105.6, 85.9, 73.7, 39.4, 39.1, 32.6, 32.4, 31.9, 23.3, 22.8, 14.2,
−0.6; IR (neat) ν 3400, 3050, 2931, 2860, 2139 cm−1; HMRS (ESI)
m/z calcd for C22H36OSiNa+ 367.2428 [M + Na+], found 367.2433.
( )-6-[(Dimethyl)phenylsilyl]oct-1-yn-4-ol (15i′): Colorless oil
(87 mg, 64%, 15i:15i′ = 17:83, indeterminable dr for 15i) obtained
according to SP2 from epoxide 9i (69 mg, 0.50 mmol). For the
27 (104 mg, 78%, 22:27 = 87:13). Further purification by flash
chromatography afforded analytically pure 22 as a white crystalline
solid: mp 49−51 °C; 1H NMR (400 MHz, CDCl3) δ 3.65−3.59 (m, 1
H), 3.39−3.34 (m, 1 H), 2.94 (m, 1 H), 2.76 (m, 1 H), 2.64 (m, 1 H),
2.21 (dt, J = 6.9, 2.3 Hz, 2 H), 2.06−2.02 (m, 1 H), 1.88−0.88 (m, 22
H); 13C NMR (100 MHz, CDCl3) δ 86.6, 79.1, 76.1, 74.3, 42.3, 40.6,
31.2, 29.2, 29.1, 28.9, 26.5, 26.2, 25.9, 22.0, 18.6, 13.7, 10.2; HMRS
1
mixture of 15i and 15i′: H NMR (400 MHz, CDCl3) δ 7.67−7.60
+
(ESI) m/z calcd for C17H31O2 267.2319 [M + H+], found 267.2322.
(m, 2 H), 7.59−7.53 (m, 2 H 15i), 7.49−7.28 (m, 3 H), 5.28 (dd, J =
6.9, 2.2 Hz, 1 H), 4.99 (t, J = 6.9 Hz, 1 H 15i), 4.14 (app qd, J = 6.9
Hz, 1 H 15i), 3.80 (app quint, J = 6.7 Hz, 1 H), 2.52 (ABX system, J =
16.8, 4.8 Hz, 1 H), 2.42 (ABX system, J = 16.8, 6.8 Hz, 1 H), 1.63−
1.55 (m, 2 H), 1.50−1.28 (m, 4 H), 0.95 (t, J = 6.9 Hz, 3 H), 0.42 (s, 6
H), 0.40 (s, 6 H 15i); 13C NMR (100 MHz, CDCl3) δ 209.5 (15i),
138.1, 137.3, 133.8 (15i), 133.7, 133.1 (15i), 129.5, 128.0, 105.4, 88.9
(15i), 85.6, 83.6 (15i), 70.5 (15i), 70.0, 37.5 (15i), 39.1, 36.0, 29.1,
27.8, 22.7, 14.1, 0.1 (15i), −0.6; IR (neat) ν 3361, 3069, 2958, 2932,
2175 (15i′), 1939 (15i) cm−1; HMRS (ESI) m/z calcd for C16H25OSi+
260.1596 [M + H+], found 260.1604.
( )-(1R*,2S*,3R*)-1-Cyclohexyl-4,4-dimethyl-2-(hex-1-ynyl)-
pentane-1,3-diol (23): Under a nitrogen atmosphere, pivalaldehyde
(0.11 mL, 1.00 mmol) was added at −80 °C to allenylzinc 11, freshly
prepared from epoxide 9a (71 mg 0.47 mmol) and nBu2Zn·2LiBr
according to SP1. The same workup as for 16 was followed to afford a
mixture of 23 and 28 (82 mg, 59%, 23:28 = 85:15) as a white
1
crystalline solid. For the mixture of 23 and 28: mp 64−65 °C; H
NMR (400 MHz, CDCl3) δ 3.21−3.47 (m, 2 H 28), 3.31−3.28 (m, 2
H), 2.89−2.87 (m, 1 H), 2.79−2.71 (m, 3 H), 2.33 (d, J = 9.6 Hz, 1 H
28), 2.21 (dt, J = 7.0, 2.3 Hz, 2 H), 2.19 (dt, J = 7.0, 2.2 Hz, 2 H 28),
2.09 (d, J = 5.8 Hz, 1 H 28), 2.06−2.01 (m, 1 H), 1.87−1.83 (m, 1 H
28), 1.78−1.64 (m, 4 H), 1.60−1.36 (m, 5 H), 1.31−1.11 (m, 3 H),
1.04−0.88 (m, 2 H), 0.98 (s, 9 H 28), 0.96 (s, 9 H), 0.90 (t, J = 7.2
Hz, 3 H); 13C NMR (100 MHz, CDCl3) δ 88.0, 87.3 (28), 81.3, 80.7,
77.3 (28), 75.8, 75.0, 41.7, 40.4, 37.5 (28), 36.7, 36.1, 35.8 (28), 31.04,
30.98 (28), 30.4 (28), 29.3, 28.9, 26.63 (28), 26.61 (28), 26.54, 26.5,
26.47, 26.3 (28), 26.25, 26.22, 26.0, 22.1, 18.7, 18.6 (28), 13.7; IR
(neat) ν 3278, 2954, 2944, 2233 cm−1; HMRS (ESI) m/z calcd for
(
)-(1R*,2r*,3S*)-1,3-Dicyclohexyl-2-(hex-1-ynyl)propane-
1,3-diol (16): Under a nitrogen atmosphere, cyclohexanecarbox-
aldehyde (0.09 mL, 0.73 mmol) was added at −80 °C to allenylzinc
11, freshly prepared from epoxide 9a (99 mg, 0.56 mmol) and
nBu2Zn·2LiBr according to SP1. The mixture was warmed to −20 °C
and stirred at this temperature for 1 h. The reaction was quenched
with aqueous 1 M HCl solution (10 mL). Et2O (10 mL) was added,
the layers were separated, and the aqueous one was extracted with
Et2O (2 × 10 mL). The combined organic layers were washed with
water (15 mL) and brine (15 mL) and dried over anhydrous MgSO4.
After removal of the solvent, the crude reaction was purified by flash
chromatography (20% Et2O/pentane) to afford a mixture of 16 and 17
(144 mg, 68%, 16:17 = 85:15) as a white crystalline solid. For the
mixture of 16 and 17: mp 113−114 °C; 1H NMR (400 MHz, CDCl3)
δ 3.59 (dd, J = 6.8, 5.4 Hz, 1 H 17), 3.50 (dd, J = 9.0, 1.9 Hz, 1 H 17),
3.36 (dd, J = 8.1, 2.3 Hz, 2 H), 2.83−2.82 (m, 1 H), 2.73−2.72 (m, 1
H 17), 2.26−2.19 (m, 2 H), 2.12−2.09 (m, 1 H 17), 2.05−2.02 (m, 2
H), 1.79−0.81 (m, 26 H), 0.92 (t, J = 7.2 Hz, 3 H) 0.90−0.87 (m, 1 H
17); 13C NMR (100 MHz, CDCl3) δ 86.5, 85.5 (17), 79.2, 76.74 (17),
76.68 (17), 79.2, 74.5, 74.2 (17), 42.6 (17), 42.3, 40.6 (17), 38.4 (17),
38.1, 31.2, 30.2 (17), 29.7, 29.4, 29.1, 28.9, 27.1 (17), 26.6, 26.5, 26.2,
26.0, 22.0, 18.7, 18.6 (17), 13.8; IR (neat) ν 3313, 2910, 2848, 2238
+
C19H34O2 295.2632 [M + H+], found 295.2637.
Mixture of ( )-(1R*,2r*,3S*)-1,3-Dicyclohexyl-2-(3,3-dime-
thylbut-1-ynyl)propane-1,3-diol (24) and ( )-(1R*,3R*)-1,3-
Dicyclohexyl-2-(3,3-dimethylbut-1-ynyl)propane-1,3-diol (29):
Under a nitrogen atmosphere, cyclohexanecarboxaldehyde (0.07 mL,
0.60 mmol) was added at −80 °C to allenylzinc 20, freshly prepared
from epoxide 9a (69 mg 0.46 mmol) and tBu2Zn·2LiBr according to
SP1. The same workup as for 16 was followed to afford a mixture of
24 and 29 (129 mg, 88%, 24:29 = 36:64) as a white crystalline solid.
For the mixture of 24 and 29: mp 156−157 °C; 1H NMR (400 MHz,
CDCl3) δ 3.58 (dd, J = 6.4, 5.7 Hz, 1 H), 3.49 (dd, J = 8.6, 1.7 Hz, 1
H), 3.36 (dd, J = 7.6, 2.8 Hz, 2 H 24), 2.79 (t, J = 2.8 Hz, 1 H), 2.70
(dd, J = 6.4, 1.7 Hz, 1 H), 2.11−2.08 (m, 2 H 24), 2.01−1.86 (m, 2
H), 1.23 (s, 9 H 24), 1.22 (s, 9 H), 1.75−0.85 (m, 22 H); 13C NMR
(100 MHz, CDCl3) δ 95.4 (24), 94.5, 78.5, 75.9, 74.9, 74.0, 72.9 (24),
42.9, 42.4, 40.8, 38.7, 38.1 (24), 31.4 (24), 31.3 (24), 30.3, 29.8, 29.3,
29.1, 28.9, 28.8, 27.7 (24), 27.6, 26.6, 26.53, 26.50. 26.4, 26.31, 26.26,
26.1, 26.0, 25.5; HMRS (ESI) m/z calcd for C21H37O2+ 321.2788 [M +
H+], found 321.2794.
+
cm−1; HMRS (ESI) m/z calcd for C21H37O2 321.2788 [M + H+],
found 321.2794.
( )-(1S,*,5r*,6R*)-4,6-Dicyclohexyl-5-(hex-1-ynyl)-1,3-diox-
ane (18): At 20 °C, to 16 (17 mg, 0.05 mmol, 16:17 = 85:15) in
dimethoxymethane (2 mL) was added PTSA (a spatula tip). After 16 h
of stirring, the reaction was quenched with a mixture of a saturated
aqueous NH4Cl solution (10 mL) and Et2O (10 mL) was added. The
layers were separated, and the aqueous one was extracted with Et2O (2
× 10 mL). The combined organic layers were washed with water (10
mL) then brine (10 mL) and dried over anhydrous MgSO4. Removal
of the solvent afforded a mixture of 18 and 19 (17 mg, 100%, 18:19 =
86:14) as a white crystalline solid. For the mixture of 18 and 19: mp
85−86 °C; 1H NMR (400 MHz, CDCl3) δ 5.14 (d, J = 6.2 Hz, 1 H),
4.89 (d, J = 6.0 Hz, 1 H 19), 4.83 (d, J = 6.0 Hz, 1 H 19), 4.61 (d, J =
6.2 Hz, 1 H), 3.60 (dd, J = 9.9, 1.5 Hz, 1 H 19), 3.27 (dd, J = 9.4, 2.5
Hz, 1 H 19), 3.04 (dd, J = 9.6, 2.2 Hz, 2 H), 2.64−2.62 (m, 1 H 19),
2.52 (br s, 1 H), 2.22 (dt, J = 6.7, 2.2 Hz, 2 H), 2.11−2.08 (m, 2 H),
1.94−1.90 (m, 2 H 19), 1.83−1.64 (m, 10 H), 1.53−1.39 (m, 4 H),
1.32−1.10 (m, 6 H), 0.93 (t, J = 7.2 Hz, 3 H), 1.00−0.74 (m, 4 H);
13C NMR (100 MHz, CDCl3) δ 94.3, 86.6 (19), 83.9, 83.7, 82.2 (19),
( )-(1R*,2S*)-1-Cyclohexyl-2-(hex-1-ynyl)-3-methylbutane-
1,3-diol (25): Under a nitrogen atmosphere, acetone (0.12 mL, 1.60
mmol) was added at −80 °C to allenylzinc 11, freshly prepared from
epoxide 9a (77 mg 0.51 mmol) and nBu2Zn·LiBr according to SP1.
The same workup as for 16 was followed to afford 25 (98 mg, 77%) as
a white crystalline solid. Also prepared in 59% yield from epoxide cis-
9a following the same procedure: mp 56−58 °C; 1H NMR (400 MHz,
CDCl3) δ 3.56−3.53 (m, 1 H), 2.89 (d, J = 5.6, 1 H), 2.69 (s, 1 H),
2.50−2.49 (m, 1 H), 2.24 (dt, J = 7.0, 2.3 Hz, 2 H), 2.14−2.08 (m, 1
H), 1.84−1.65 (m, 4 H), 1.65−1.38 (m, 5 H), 1.35 (s, 3 H), 1.31 (s, 3
H), 1.29−1.10 (m, 3 H), 1.00−0.80 (m, 2 H), 0.91 (t, J = 7.2 Hz, 3
H); 13C NMR (100 MHz, CDCl3) δ 86.8, 75.8, 74.9, 73.0, 45.8, 42.8,
31.2, 29.7, 29.4, 29.0, 27.1, 26.5, 26.1, 26.0, 22.1, 18.6, 13.7; IR (neat)
ν 3354, 2922, 2852, 2232 cm−1; HMRS (ESI) m/z calcd for
+
C17H30O2 267.2319 [M + H+], found 267.2324.
(
)-(3S*,4R*)-3-[(Dimethyl)phenylsilyl]ethynyl-5-ethyl-2-
81.8 (19), 79.0 (19), 77.7 (19), 75.0, 39.9 (19), 39.8, 35.8 (19), 33.1,
31.3, 31.2 (19), 31.0 (19), 29.8 (19), 29.7, 29.6 (19), 29.1, 27.6 (19),
27.5, 26.7, 26.4, 26.1, 26.0, 25.9 (19), 25.8, 25.7, 22.04 (19), 21.98,
18.7, 13.8; HMRS (ESI) m/z calcd for C22H37O2+ 333.2788 [M + H+],
found 333.2790.
( )-(1R*,2R*,3S*)-1-Cyclohexyl-2-(hex-1-ynyl)pentane-1,3-
diol (22): Under a nitrogen atmosphere, propanal (0.07 mL, 1.00
mmol) was added at −80 °C to allenylzinc 11, freshly prepared from
epoxide 9a (75 mg 0.50 mmol) and nBu2Zn·2LiBr according to SP1.
The same workup as for 16 was followed to afford a mixture of 22 and
methylheptane-2,4-diol (26): Under a nitrogen atmosphere,
acetone (0.19 mL, 2.50 mmol) was added at −80 °C to allenylzinc
21, freshly prepared from epoxide 9c (69 mg 0.50 mmol) and
(PhMe2Si)2Zn·2LiBr according to SP2. The mixture was warmed to
−40 °C over a period of 10 min and stirred at this temperature for 2.5
h. The same procedure workup as for 16 was followed, and the crude
material was purified by flash chromatography (40% CH2Cl2/
1
cyclohexane) to afford 26 (70 mg, 42%) as a yellow oil: H NMR
(400 MHz, CDCl3) δ 7.68−7.64 (m, 2 H), 7.42−7.36 (m, 3 H), 4.11
143
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(dd, J = 8.6, 1.7 Hz, 1 H), 2.77 (d, J = 1.7 Hz, 1 H), 1.72−1.65 (m, 1
H), 1.63−1.55 (m, 1 H), 1.55−1.40 (m, 1 H), 1.44 (s, 3 H), 1.39 (s, 3
H), 1.23−1.37 (m, 1 H), 0.91 (t, J = 7.4 Hz, 3 H), 0.88 (t, J = 7.5 Hz, 3
H), 0.45 (s, 6 H); 13C NMR (100 MHz, CDCl3) δ 137.4, 133.8, 129.7,
128.1 105.4, 89.5, 73.0, 71.7, 47.7, 45.5, 29.6, 27.7, 21.2, 20.6, 10.8,
10.7, −0.4; IR (neat) ν 3355, 3069, 2961, 2169 cm−1; HMRS (ESI)
m/z calcd for C20H32O2SiNa+ 355.2064 [M + Na+], found 355.2065.
Bernard, N.; Normant, J. F. Tetrahedron Lett. 1998, 39, 6715−6718.
(f) Chemla, F.; Bernard, N.; Normant, J. F. Tetrahedron Lett. 1998, 39,
8837−8840.
(11) (a) Chemla, F.; Bernard, N.; Ferreira, F.; Normant, J. F. Eur. J.
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1567.
́
ez-Luna, A.; Roy, B. New J. Chem. 2007, 31, 1552−
ASSOCIATED CONTENT
■
(12) Denichoux, A.; Chemla, F.; Ferreira, F. Org. Lett. 2004, 6,
3509−3512.
(13) The reaction of allenyl- and propargylmetals with non-
coordinating electrophiles, such as water, is assumed to proceed by
an acyclic SE2 process. The 10a:10a′ ratio obtained thus perfectly
reflects the 11:11′ ratio in the metallotropic equilibrium. See for
example ref 8.
(14) (a) Kurz, A. L.; Beletskaya, I. P.; MacVas, A.; Reutov, O. A.
Tetrahedron Lett. 1968, 3679−3682. (b) Nee, G.; Leroux, Y.; Penne, J.
S. Tetrahedron 1981, 37, 1541−1545. (c) Reich, H. J.; Green, D. P. J.
Am. Chem. Soc. 1989, 111, 8729−8731. (d) Reich, H. J.; Borst, J. P.;
Dykstra, R. R.; Green, D. P. J. Am. Chem. Soc. 1993, 115, 8728−8741.
(15) (a) Fleming, I.; Roberts, R. S.; Smith, S. J. Chem. Soc., Perkin
Trans. 1 1998, 1209−1214. (b) Oestreich, M.; Weiner, B. Synlett 2004,
2139−2142. (c) For a very recent use of bis(dimethylphenylsilyl)zinc
in the nucleophilc silicon addition to propragylic chlorides and
phosphates via a direct SN2′ pathway, see ref 2c.
(16) Although the pseudo-symmetrical 2-alkynyl-syn-1,3-diol motif
has not been described yet in the literature, related 2-alkyl-substituted
structures have been reported. See for example: (a) Maynes, G. J.;
Applequist, D. E. J. Am. Chem. Soc. 1973, 95, 856−861. (b) Anwar, S.;
Bradley, G.; Davis, A. P. J. Chem. Soc., Perkin Trans. 1 1991, 1383−
1389. (c) Bartoli, G.; Bellucci, M. C.; Bosco, M.; Dalpozzo, R.;
Marcantoni, E.; Sambri, L. Chem.Eur. J 2000, 6, 2590−2598.
(d) Kalaitzakis, D.; Smonou, I. Tetrahedron 2010, 66, 9431−9439.
(e) Gogoi, P.; Kotipalli, T.; Indukuri, K.; Bondalapati, S.; Saha, P.;
Saikia, A. K. Tetrahedron Lett. 2012, 53, 2726−2729.
S
* Supporting Information
Experimental procedures; 1H and 13C spectra of new
compounds; crystallographic data for compound 24. This
material is available free of charge via the Internet at http://
pubs.acs.org.
AUTHOR INFORMATION
Corresponding Author
*Fax: (+33) 144-27-75-67. E-mail: fabrice.chemla@upmc.fr,
franck.ferreira@upmc.fr.
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
The authors wish to kindly thank the MESR for grants to A.D.
and M.C., and Patrick Herson for the determination of the X-
ray structure of compound 24.
DEDICATION
Dedicated to the memory of Robert E. Ireland.
■
REFERENCES
■
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The Journal of Organic Chemistry
Article
(23) X-ray crystal data of compound 24: C26H36O2; Mw = 320.52;
colorless; crystal size 0.08 × 0.12 × 0.19 mm; monoclinic; space group
P21/c; Z = 4; a = 9.7491(15), b = 21.6842(77), c = 9.9916(14) Å, α =
90.000, β = 105.950(11), γ = 90.000(11)°; V = 2035.5(5) Å3; ρcalcd
=
1.05 g cm−3; λ = 0.710730 Å (Mo Kα); μ = 0.065 cm−1; KAPPA type
diffractometer; temperature 250 K; θ range 1−25°; min/max h = −13/
13, min/max k = −30/23, min/max l = −10/14; 19 046 measured
reflections, 5879 independent, 3159 used, 209 parameters; R = 0.051
(R = Σ∥F0| − |Fc∥/Σ|F0|), Rw = 0.057 (Rw = [Σw(∥F0| − |Fc∥)2/
2
ΣwF0 ]1/2), goodness of fit = 1.013, max/min Δρ = −0.17/0.27 e Å−3.
CCDC903504 contains the supplementary crystallographic data for
this paper. These data can be obtained free of charge from The
Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/
data_ request/cif.
(24) Suffert, J. J. Org. Chem. 1989, 54, 509−510.
145
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