Chiral propargylic cations as intermediates in SN1-type reactions: Substitution pattern, nuclear magnetic resonance studies, and origin of the diastereoselectivity

Article abstract of DOI:10.1021/ja411772n

Nine propargylic acetates, bearing a stereogenic center (-C*HXR ²) adjacent to the electrophilic carbon atom, were prepared and subjected to S_N1-type substitution reactions with various silyl nucleophiles employing bismuth trifluoromethanesulfonate [Bi(OTf)₃] as the Lewis acid. The diastereoselectivity of the reactions was high when the alkyl group R² was tertiary (tert-butyl), irrespective of the substituent X. Products were formed consistently with a diastereomeric ratio larger than 95:5 in favor of the anti-diastereoisomer. If the alkyl substitutent R² was secondary, the diastereoselectivity decreased to 80:20. The reaction was shown to proceed stereoconvergently, and the relative product configuration was elucidated. The reaction outcome is explained by invoking a chiral propargylic cation as an intermediate, which is preferentially attacked by the nucleophile from one of its two diastereotopic faces. Density functional theory (DFT) calculations suggest a preferred conformation in which the group R² is almost perpendicular to the plane defined by the three substituents at the cationic center, with the nucleophile approaching the electrophilic center opposite to R². Transition states calculated for the reaction of allyltrimethylsilane with two representative cations support this hypothesis. Tertiary propargylic cations with a stereogenic center (-C* HXR²) in the α position were generated by ionization of the respective alcohol precursors with FSO₃H in SO₂ClF at -80 C. Nuclear magnetic resonance (NMR) spectra were obtained for five cations, and the chemical shifts could be unambiguously assigned. The preferred conformation of the cations as extracted from nuclear Overhauser experiments is in line with the preferred conformation responsible for the reaction of the secondary propargylic cations.

Full text of DOI:10.1021/ja411772n

Article
pubs.acs.org/JACS
Chiral Propargylic Cations as Intermediates in SN1‑Type Reactions:
Substitution Pattern, Nuclear Magnetic Resonance Studies, and
Origin of the Diastereoselectivity
Dominik Nitsch,† Stefan M. Huber,† Alexander Pothig,† Arjun Narayanan,‡ George A. Olah,‡
̈
G. K. Surya Prakash,‡ and Thorsten Bach*,†
†Department Chemie and Catalysis Research Center (CRC), Technische Universitat Munchen, D-85747 Garching, Germany
̈
̈
‡Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, Los Angeles, California
90089-1661, United States
S
* Supporting Information
ABSTRACT: Nine propargylic acetates, bearing a stereogenic center (−C*HXR2) adjacent to the electrophilic carbon atom,
were prepared and subjected to SN1-type substitution reactions with various silyl nucleophiles employing bismuth
trifluoromethanesulfonate [Bi(OTf)3] as the Lewis acid. The diastereoselectivity of the reactions was high when the alkyl
group R2 was tertiary (tert-butyl), irrespective of the substituent X. Products were formed consistently with a diastereomeric ratio
larger than 95:5 in favor of the anti-diastereoisomer. If the alkyl substitutent R2 was secondary, the diastereoselectivity decreased
to 80:20. The reaction was shown to proceed stereoconvergently, and the relative product configuration was elucidated. The
reaction outcome is explained by invoking a chiral propargylic cation as an intermediate, which is preferentially attacked by the
nucleophile from one of its two diastereotopic faces. Density functional theory (DFT) calculations suggest a preferred
conformation in which the group R2 is almost perpendicular to the plane defined by the three substituents at the cationic center,
with the nucleophile approaching the electrophilic center opposite to R2. Transition states calculated for the reaction of
allyltrimethylsilane with two representative cations support this hypothesis. Tertiary propargylic cations with a stereogenic center
(−C*HXR2) in the α position were generated by ionization of the respective alcohol precursors with FSO3H in SO2ClF at −80
°C. Nuclear magnetic resonance (NMR) spectra were obtained for five cations, and the chemical shifts could be unambiguously
assigned. The preferred conformation of the cations as extracted from nuclear Overhauser experiments is in line with the
preferred conformation responsible for the reaction of the secondary propargylic cations.
some time ago by studying the reaction of propargylic acetates,
which bear a stereogenic 2-(3,3-dimethyl)butyl substituent
(−CHMetBu) at the electrophilic carbon center.10 It was found
that the reaction with aromatic nucleophiles (NuH) and
silylated nucleophiles (NuTMS), such as silyl enol ethers and
allylsilanes, proceeds with high diastereoselectivity. As an
example, the reaction of acetate 1 is shown in Scheme 1. It
delivered the respective anti-products 3 upon treatment with a
nucleophile and with 10 mol % Bi(OTf)3 (Tf = trifluoro-
methanesulfonyl) in nitromethane as the solvent. The reaction
was shown to be stereoconvergent; i.e., the relative
INTRODUCTION
■
The nucleophilic displacement of an appropriate leaving group
by a carbon nucleophile at a propargylic alcohol or its derivative
represents a useful synthetic transformation.1 Despite the
progress made in SN1-type bond formation reactions starting
from propargylic alcohols,2−4 propargylic esters,5 or propargylic
ethers,6 there is little information about the stereochemical
course of this substitution if a stereogenic center resides in the
α position to the electrophilic center. Indeed, the limited
knowledge on the facial diastereoselectivity of nucleophilic
addition reactions at prostereogenic cationic carbon centers7,8
is striking if compared to the extensive data set that has been
accumulated over the years on the addition of strong
nucleophiles to chiral aldehydes.9 We addressed this issue
Received: November 21, 2013
© XXXX American Chemical Society
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acetylation of the respective alcohol,12 which, in turn, was
prepared by addition of a PMP-substituted (PMP = para-
methoxyphenyl) ethynyllithium reagent13 to 3,3-dimethyl-2-
methoxybutanal (see the Supporting Information for further
details).14
Scheme 1
Initial screening was conducted with different Lewis acids,
which promote the reaction of acetate 4 with a silyl enol
ether.15 Yields were highest with Bi(OTf)3, which was used as
the catalyst throughout this study.16 The reaction of acetate 4
with various silylated nucleophiles proceeded with high
diastereoselectivity and produced anti-5 frequently as the only
observed product (Table 1).
configuration of the substrate had no influence on the product
configuration, supporting the intermediacy of cation 2 in the
reaction course.
Table 1. Diastereoselective Reaction of Propargylic Acetate
4 with Various Silylated Nucleophiles to Products 5
To explain the outcome of the reaction, the conformation of
cations, such as 2, was analyzed by density functional theory
(DFT) calculations and a local minimum was found, in which a
preferred attack from one face was favored. The results were,
however, not verified by further calculations on the transition
state of the reactions. The scope was limited to substrates with
the same propargylic unit and with a single stereogenic
substituent. To obtain a more comprehensive picture on the
intriguing issue of acylic stereocentrol in carbocation
reactions,11 we have now extended the substrate scope to
propargylic acetates of general structure A (Figure 1), in which
Figure 1. General structure of propargylic acetates A, which were
employed in this study, and general structure of the cations B derived
from A with the dihedral angle Θ being defined with a positive rotation
in the direction R1 → H.
a
the substituents X and R2 were varied. Stable carbocations B
were generated from acetates A (R1 = Me) under superacidic
conditions to obtain information on their constitution and
conformation in solution. In addition, the transition states of
the reaction with an allylsilane as a representative nucleophile
were analyzed by DFT calculations. Details of this work are
reported in the present account.
Reactions were performed in deaerated MeNO2 (c = 125 mM) within
30 min (entries 6 and 7) and 60 min (entries 1−5) at ambient
temperature. Yield of isolated product after chromatographic
purification. The diastereomeric ratio (dr = anti/syn) was determined
by H NMR analysis of the crude product mixture.
b
c
1
In the case of product 5a, it was shown that the product
configuration was independent of the relative configuration of
the starting material. Irrespective of whether acetate 4 was used
as the anti-diastereoisomer (dr = 95:5) or as a mixture of
diastereoisomers (dr = 58:42), product 5a was obtained as a
single product. The reaction proceeded stereoconvergently,
which clearly rules out a SN2-type displacement. Most silyl enol
ethers and silyl ketene acetals reacted smoothly (entries 1−4)
and showed no indication of a SN′-type substitution (i.e., a
reaction at the distal position of the propargylic cation). Only
with a sterically congested silyl ketene acetal (entry 5), a major
side product was observed (see the Supporting Information),
which can be explained by an initial SN′ attack. The less reactive
allylsilanes (entries 6 and 7) gave slightly lower yields than the
silyl enol ethers. Diastereoselectivites were high, however, and
could be further improved at low temperatures. When the
reaction of entry 6 was performed under otherwise identical
conditions at 0 °C, the dr was >95:5 (63% yield).
RESULTS AND DISCUSSION
■
Synthetic Studies with Various Substrates of Type A.
In the first set of experiments, nucleophilic substitution
reactions were performed with precursors for propargylic
carbocations, which bear a methoxy group (X = OMe; Figure
1) at the adjacent stereogenic center. As previously observed
(Scheme 1), acetates were superior substrates compared to
alcohols, which were not sufficiently reactive, and compared to
the very labile mesylates. Acetate 4 (Scheme 2) was obtained by
Scheme 2
To chemically ascertain the relative configuration of the
propargylic substitution products, the substituent X (Figure 1)
was modified (Scheme 3). The 2,6-dichlorobenzyl group was
B
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As already seen for substrates 6, a change of the substituent
R2 (Figure 1) from tert-butyl to isopropyl led (while leaving all
other parameters constant) to a decrease in diastereoselectivity.
When comparing the reactions 4 → 5a with the reaction 11 →
12a, a similar chemoselectivity (84% versus 75% yield) but a
reduced diastereoselectivity (dr = >95:5 versus 74:26) was
recorded at ambient temperature. If the reaction temperature
was lowered in the latter case to 0 °C (Scheme 5), the time
Scheme 3
Scheme 5
required to achieve full conversion increased to 4 h (in
comparison to 1 h at ambient temperature), with the
diastereoselectivity increasing slightly to 79:21. With the silyl
ketene acetal derived from phenyl acetate, the respective
product 12b was formed under the same conditions (0 °C and t
= 4 h) in a yield of 69% and with a diastereomeric ratio of dr =
80:20.
Because the reactions with the α-methoxy group (X = OMe;
Figure 1) were mostly performed with a terminal PMP
substituent at the alkyne group (substrates 4, 6, and 11), a
set of experiments was conducted in which the previously
studied10 −CHMetBu stereogenic unit (Scheme 1) and its R2
variants (R2 = i-Pr and Et) were probed with propargylic PMP-
substituted acetates of type 13 (Scheme 6). The chemical yield
employed as a cleavable protecting group, which liberates a free
hydroxy group upon deprotection. The resulting alcohol, in
turn, was expected to close to a γ-lactone ring by a
transesterification. The diastereoselectivities in the SN1-type
displacement reaction with the silyl nucleophile remained
essentially unchanged for substrate 6a compared to substrate 4.
The diastereoselectivity for substrate 6b, bearing an isopropyl
group instead of a tert-butyl group at the stereogenic center,
was lower than that for substrate 6a, and the formation of a
second diastereoisomer was observed. Without purification,
products 7 were treated with hydrogen and, as expected, the
formation of lactones 8 was observed. Their relative
configuration was proven by nuclear Overhauser effect
(NOE) studies. In addition, the coupling pattern for the
hydrogen atom at C5 in products 8 matched the known
coupling pattern of closely related cis- and trans-substituted γ-
lactones.17 The chemical assignment of the relative config-
uration was further corroborated for R2 = t-Bu (Figure 1) by
crystallographic evidence (see the Supporting Information for
further details).
Scheme 6
The terminal substituent R (Figure 1) at the propargyl triple
bond could be altered from PMP to the synthetically less useful
phenyl group. The reactivity of the latter substrate is lower than
that of acetate 4, presumably because of the lower electron-
donating property of the phenyl group (see the Supporting
Information for further details). A more versatile substituent is
the phenylsulfanyl group and the corresponding acetate 9
(Scheme 4) was readily prepared from 3,3-dimethyl-2-
methoxybutanal in analogy to substrate 4.18 Under Bi(OTf)3
catalysis, allyltrimethylsilane delivered enyne 10a in good yield
and with high diastereoselectivity (dr = 93:7). Substitution by
an enolate equivalent was achieved with a silyl enol ether,
producing alkynone 10b as a single diastereoisomer.
and diastereoselectivity obtained where R2 = t-Bu (product
14a) was excellent, but while the yields remained high for
products 14b and 14c, the diastereoselectivity decreased in the
order R2 = t-Bu > i-Pr > Et.
Mechanistic Considerations and DFT Calculations.
From the data accumulated from the synthetic work, it is
apparent that a high preference for the formation of the anti-
product depends upon the presence of a bulky substituent R2. A
decrease in selectivity was observed when this substituent was
changed from tertiary (t-Bu) to secondary (i-Pr), while a
primary substituent was poorly selective (Scheme 6). Our
studies indicate that there is no electronic influence of the
substituent X (X = Me, OMe, and OCH2Ar), with the reaction
outcome not altered if R2 remains the same. Moreover, the
alkynyl substituent (R) also shows no influence on the facial
diastereoselectivity observed. In a first approach toward a
possible explanation for the selectivity, we studied the
conformation of eight different cations 15 with the R
Scheme 4
C
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substituent kept constant (R = PMP) and the substituents X,
R1, and R2 varied. The DFT calculations were performed with
the Gaussian0919 suite of programs using the B3LYP20 density
functional with the 6-311++G** basis set (similar results were
obtained using the M06-2X21 density functional), scanning the
torsion angles at intervals of 15°. As previously found for X =
Me, R1 = H, and R2 = t-Bu,10 the secondary cations (R1 = H)
show two conformational minima, 15′ and 15″ (Figure 2). For
correctly explains the experimentally observed anti-product and
is in line with the size influence at R2.
To further substantiate the above-mentioned mechanistic
picture, DFT calculations were performed, which simulate an
approach of allyltrimethylsilane to cations 15b (X = Me, R1 =
H, and R2 = t-Bu) and 15d (X = OMe, R1 = H, and R2 = t-Bu).
The corresponding transition states were modeled using the
M06-2X21 density functional and the 6-311++G** basis set,
and their nature was confirmed by the presence of one
imaginary frequency matching the expected carbon−carbon
bond formation. Grimme’s D3 dispersion correction,22 as
implemented in Gaussian09,19 was also employed for the
optimization. To test for solvent effects, single-point calcu-
lations on the gas-phase-optimized structures were performed
with the SMD23 intrinsic solvation model using the parameters
for nitromethane.
In both cases (X = Me and OMe), we found that the
transition state TS″, in which the nucleophile approaches the
cation from the bottom side (Figure 4), was lower in energy
than the transition state TS′. As a result, the former approach is
favored, thus providing an explanation for the experimentally
observed anti-product.
Figure 2. Structure and preferred conformation of cations 15 with
varying groups R1 (R = H and Me), R2 (R = i-Pr and t-Bu), and X (X
= Me and OMe) and direction of attack for syn- and anti-product
formation.
α-alkyl-substituted propargylic cations (X = Me), the dihedral
angle Θ (see Figure 1) of the global minimum is close to 180°
(15′), whereas the second minimum is characterized by a
dihedral angle of about 315° (15″). In contrast, the global
minimum of α-alkoxy-substituted cations (X = OMe) shows a
dihedral angle of 315° (15″) and a dihedral angle of about 180°
for the second relative minimum (15′). In all of these cases, the
second relative minimum is 0.9−5.3 kJ mol−1 higher in energy
than the global minimum. For tertiary cations (R1 = Me), the
first conformational minimum shifts to a smaller dihedral angle
of about 150°, while the second minimum is observed for a
dihedral angle of ca. 340°. The energy difference between the
two minima is small (0.6−3.3 kJ mol−1). The conformational
analysis of cation 15d (X = OMe, R1 = H, and R2 = t-Bu) is
shown in Figure 3, while the conformational analyses for the
other cations 15a−15c (R1 = H) and 15e−15h (R1 = Me) are
compiled in the Supporting Information.
Figure 4. Energy differences between the transition states for the
attack of allyl trimethylsilane to cations 15b (X = Me) and 15d (X =
OMe) from the disfavored (TS′) or favored (TS″) side, as obtained by
DFT calculations (M06-2X-D3 and 6-311+G**).
The structure of the favored transition state TS″ for the
reaction involving 15b is shown in Figure 5. Structures of all
other calculated transition states are provided in the Supporting
Information. A prominent difference between the two
transition states are the dihedral angles Θattack formed between
the Calkyne−Ccation bond of the cation and the double bond of
the nucleophile. While the attack of allyltrimethylsilane occurs
Figure 3. Conformational analysis of cation 15d (X = OMe, R1 = H,
and R2 = t-Bu) on the basis of DFT calculations (B3LYP 6-311+
+G**).
In Figure 2, the required direction of nucleophilic attack is
indicated for the formation of syn- and anti-products. The fact
that the anti-selectivity decreases for R2 = t-Bu > i-Pr > Et is
difficult to match with a reactive conformation 15′. In
conformation 15″, however, the group R2 adopts an almost
antiperiplanar orientation to a nucleophile approaching from
the bottom side. The direction of the nucleophilic attack
Figure 5. DFT-optimized structures of the preferred transition state
TS″ for the reaction of allyltrimethylsilane and cation 15b. Red,
oxygen; gray, carbon; white, hydrogen; and bronze, silicon. The figure
was prepared with CYL view.24
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in an almost perpendicular fashion in TS′ (Θattack = 95°), this
angle is markedly larger for TS″ (Θattack = 129°). In contrast, all
relevant bond lengths in the cation and the nucleophile are very
similar in both transition states. This includes the distance
between the carbon atoms of the newly formed bond, which is
2.42 Å for TS′ and 2.43 Å for TS″.
product formation, indicating the high stability of these
1
intermediates. Clean H and 13C NMR spectra were obtained
for the cations 15e, 15g, 15i, 15j, and 15k with all signals
assigned. To illustrate, the 13C NMR spectrum of cation 15e is
shown in Figure 6. The 13C NMR chemical shifts of carbon
Nuclear Magnetic Resonance (NMR) Spectroscopy
Studies. Chiral propargylic cations have not yet been studied
in solution, and to our knowledge, there is no information
about their constitution or conformation. It seemed therefore
appropriate to supplement the synthetic studies and DFT
1
calculations by H and 13C NMR spectroscopic investigations
of propargylic cations in superacidic solution.25 Mechanistically,
it was interesting to see whether any interactions between the
substituent X and the cationic center exist. For X = OMe, for
example, the formation of an onium ion was conceivable.
Ionization experiments with different superacids (FSO3H and
SbF5/FSO3H) were undertaken to find the optimal conditions
for the preparation of the carbocations. Unfortunately, it turned
out that neither α-alkoxy-substituted nor α-alkyl-substituted
secondary (R1 = H) propargylic alcohols led to stable cations.
Instead, a mixture of undefined products was formed under a
variety of conditions. To overcome this problem, the
corresponding tertiary (R1 = Me) alcohols were synthesized
by simple oxidation of the secondary alcohols and subsequent
addition of methyllithium. The synthesis of tertiary alcohols
with R2 = t-Bu was not attempted because it is known that the
respective cations readily undergo β-elimination with concom-
itant formation of the tert-butyl cation and derived products.26
Instead, cation precursors were prepared with R2 = i-Pr, Et, and
X varied to be methyl, methoxy, and 2,6-dichlorophenylme-
thoxy (OBnCl2). Treatment of the tertiary alcohols with
FSO3H in SO2ClF at −80 °C quantitatively generated the
cations 15e, 15g, 15i, 15j, and 15k (Scheme 7 and Table 2).
Figure 6. 13C NMR spectrum of cation 15e (acetone-d6 as the external
standard).
atoms C1, C2, and C3 are given in Table 2. As previously
observed for para-methoxy-substituted benzylic carboca-
tions,8g,27 two sets of signals were visible in the 13C NMR
spectra of cations 15j and 15k, whereas cation 15g showed
broad signals for the aromatic ortho- (CB) and meta- (CC)
carbon atoms. The alkyl-substituted cations (X = Me) 15e and
15i exhibited only a single set of signals. The peak broadening
or peak separation for the oxygen-substituted cations 15g, 15j,
and 15k suggests two diastereomeric structures resulting from
the hindered rotation of the methoxy substitutent of the PMP
group. The partial double bond character of the bond between
the para-carbon atom CD and the oxygen atom leads to a
mixture of E and Z isomers.
Scheme 7
The described effect is well-precedented for PMP-substituted
alkyl cations.27 The rotational barrier around the C−O bond
has been shown to be a benchmark for the stabilization of the
respective cation by its adjacent substituents. It increases if non-
bonding electron pairs of the oxygen atom are required for
cation stabilization because of an inefficient stabilization by
neighboring substituents.28 For the present case, it follows29
that the α-alkoxy-substituted cations 15g, 15j, and 15k need to
be additionally stabilized by the PMP group, while the alkyl-
substituted cations 15e and 15i require less stabilization.
The significant deshielding of C1 and C3 relative to their
alcohol precursors indicates a substantial mesomeric stabiliza-
tion by the triple bond (allenyl cation as the resonance
structure). When the chemical shifts are compared to those
observed by Olah et al. for a tertiary, non-chiral propargylic
carbocation of type B (Figure 1; R = Ph, R1 = Me, and X and
R2 = H), we find good agreement with our results.30 In this
cation, carbon atoms C1 and C3 show a downfield shift to 199
and 237 ppm, respectively, which is in the same range as
observed for cations 15e, 15g, 15i, 15j, and 15k. Carbon atom
C2 is less deshielded (δ = 124 ppm) than C1 and C3, which also
matches our experimental data (Table 2).
The weakly yellow solutions of the cation precursors turned
into deep red (15e, 15j, and 15k), deep yellow (15g), and deep
brown (15i) solutions in the acidic solvent.
Storing these carbocations under superacidic conditions in
SO2ClF at −30 °C for several days and cooling them back to
−80 °C did not lead to significant decomposition or side
Table 2. Substitution Pattern and 13C NMR Shift Data for
a
Cations 15e, 15g, 15i, 15j, and 15k
cation
X
R2
C1 (ppm)
C2 (ppm)
C3 (ppm)
15e
15g
15i
15j
15k
Me
i-Pr
i-Pr
Et
197.3
178.7
197.3
179.9
180.4
114.4
114.7
114.4
116.1
116.3
215.8
196.0
215.1
198.2
198.4
OMe
Me
On the basis of the relatively strong downfield shift of carbon
atoms C3 in cations 15g, 15j, and 15k, bridged onium ions are
unlikely as cyclic intermediates in the SN1-type substitution
reaction.31 While a significant downfield shift would be
OBnCl2
OBnCl2
Et
i-Pr
a
FSO3H−SO2ClF, external standard acetone-d6, and 193 K.
E
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expected for the methoxy carbon atom or the benzylic
methylene group in a bridged onium ion, a minimal shift of 4
ppm in the 13C NMR spectrum for these atoms excludes the
existence of a positive charged oxygen atom. Additional
synthetic work (see the Supporting Information) supported
the existence of a propargylic cation with a flexible linkage to its
neighboring stereogenic substituent.
OMe and OCH2Ar) is less pronounced. There is no indication
for these groups to adopt a position perpendicular to the cation
plane or to stabilize the cation via a non-bonding oxygen
orbital. The former observation is striking given that alkoxy
groups prefer a perpendicular position relative to the carbonyl
group,14a,32 in addition to reactions of strong nucleophiles to
carbonyl compounds.33
Apart from the constitutional information, it was also
ASSOCIATED CONTENT
* Supporting Information
Detailed experimental procedures, characterization data for new
compounds, X-ray crystallographic data, and details of the DFT
calculations. This material is available free of charge via the
Internet at http://pubs.acs.org.
possible to extract some information about the conformation
■
1
S
of the propargylic carbocations. The H NMR spectrum of
cations 15e, 15g, and 15k were well-resolved, and a strong
NOE contact was observed between the methyl group at the
cationic carbon and the hydrogen atom at the stereogenic
center. This contact supports a preferred conformation 15″
(Figure 2), as depicted in Figure 7 for cation 15g.
AUTHOR INFORMATION
Corresponding Author
thorsten.bach@ch.tum.de
■
Notes
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
This project was supported by the Deutsche Forschungsge-
meinschaft (Ba 1372/12-2) and by the Fonds der Chemischen
Industrie (Kekule scholarship to Dominik Nitsch and Liebig
́
scholarship to Stefan M. Huber). The NMR studies were
supported by the Loker Hydrocarbon Research Institute.
Figure 7. Preferred conformation of cation 15g based on the indicated
NOE contact.
■
In preliminary experiments toward the generation of
secondary propargylic cations, we successfully prepared cation
17 from propargylic alcohol 16 (Scheme 8). The cation is the
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CONCLUSION
■
As a result of our study, the stereochemical outcome of SN1-
type substitution at various propargylic substrates with an α-
stereogenic center (−C*HXR2) can now be understood.
Intermediate cations are attacked in a conformation in which
secondary or tertiary alkyl groups R2 are positioned almost
perpendicular (70−110°) to the plane defined by the three
substituents at the cationic carbon atom. The hydrogen atom at
the stereogenic center shows a dihedral angle Θ of 310−350°
relative to the hydrogen atom at the secondary cation center.
On the basis of DFT calculations, these conformations
represent minima for secondary and tertiary cations. For
tertiary propargylic cations, proof for the preferred conforma-
tion was obtained by NOE experiments. Attack occurs anti to
the alkyl groups R2 and leads to the respective anti-products
with high selectivity (dr ≥ 90:10) for tertiary R2 and with lower
selectivity (dr ≅ 80:20) for secondary R2 groups. It is surprising
that the electronic influence of electron-donating groups (X =
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