Sodium Diisopropylamide in Tetrahydrofuran: Selectivities, Rates, and Mechanisms of Alkene Isomerizations and Diene Metalations

Article abstract of DOI:10.1021/jacs.7b05218

Sodium diisopropylamide in tetrahydrofuran is an effective base for the metalation of 1,4-dienes and isomerization of alkenes. Dienes metalate via tetrasolvated sodium amide monomers, whereas 1-pentene is isomerized by trisolvated monomers. Facile, highly Z-selective isomerizations are observed for allyl ethers under conditions that compare favorably to those of existing protocols. The selectivity is independent of the substituents on the allyl ethers; rate and computational data show that the rates, mechanisms, and roles of sodium-oxygen contacts are substituent-dependent. The competing influences of substrate coordination and solvent coordination to sodium are discussed.

Full text of DOI:10.1021/jacs.7b05218

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Article
Sodium Diisopropylamide in Tetrahydrofuran: Selectivities, Rates,
and Mechanisms of Alkene Isomerizations and Diene Metalations
Russell F. Algera, Yun Ma, and David B. Collum
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.7b05218 • Publication Date (Web): 22 Jul 2017
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Sodium Diisopropylamide in Tetrahydrofuran:
Selectivities, Rates, and Mechanisms of
Alkene Isomerizations and Diene Metalations
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Russell F. Algera, Yun Ma, and David B. Collum*
Department of Chemistry and Chemical Biology
Baker Laboratory, Cornell University
Ithaca, New York 14853–1301
E-mail: dbc6@cornell.edu
Abstract
Sodium diisopropylamide in tetrahydrofuran is an effective base for the
metalation of 1,4-dienes and isomerization of alkenes. Dienes metalate via
tetrasolvated sodium amide monomers, whereas 1-pentene is isomerized by
trisolvated monomers. Facile, highly Z-selective isomerizations are observed
for allyl ethers under conditions that compare favorably to those of existing
protocols. The selectivity is independent of the substituents on the allyl
ethers; rate and computational data show that the rates, mechanisms, and
roles of sodium–oxygen contacts are substituent-dependent. The competing
influences of substrate coordination and solvent coordination to sodium are
discussed.
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Introduction
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Sodium diisopropylamide (NaDA) is a case study of reagent
popularity within the synthetic organic community. First prepared by Levine
in 1959,1 NaDA is demonstrably more reactive than lithium
diisopropylamide (LDA).2 During the intervening half century, however,
NaDA has been used in approximately a dozen studies,3 whereas LDA is
probably used thousands of times daily. What explains this huge disparity?
We believe inconvenience plays a role: NaDA is insoluble in inert
hydrocarbons and unstable in solubilizing ethereal solvents, which makes it
difficult to handle as stock solutions.
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From previous studies of lithium amides solvated by simple
trialkylamines4—an overlooked and underappreciated class of solvents—we
surmised that NaDA might be soluble and stable. Indeed, 1.0 M solutions of
NaDA in N,N-dimethylethylamine (DMEA), N,N-dimethylbutylamine, or N-
methylpyrrolidine are homogeneous and stable for weeks at room
temperature and for months and possibly years with refrigeration.
NaDA/trialkylamine solutions can be prepared in 15 min from unpurified
commercial reagents, which means that long-term storage is unnecessary.
As strange as it may sound, organosodium chemistry is likely in its
infancy.5,6
Our first study illustrated the synthetic importance of NaDA in
DMEA by metalating a dozen functionally diverse substrates and comparing
the rates and selectivies with LDA in tetrahydrofuran (THF).7 Subsequent
structural studies showed that NaDA is dimeric when solvated by a number
of mono-, di-, and trifunctional solvents.8 Tetrasolvated dimer 1 is germane
to the work described herein.
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The current study explored NaDA-mediated metalations of alkenes
and dienes in THF to probe the role of aggregation and solvation (Scheme
1). We examined whether potentially coordinating substituents influence rate
and mechanism through direct sodium–ligand interactions or through
induction.
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Scheme 1. Summary of alkene and diene metalation with NaDA/THF.
Results
General. Stock solutions of 1.0 M NaDA in DMEA were prepared as
described previously.7 (The importance of using fresh sodium dispersion
cannot be overstated.) NaDA was crystallized from DMEA/hexane for
spectroscopic and rate studies despite no evidence that this added precaution
has a significant effect.8 Solutions of NaDA in neat DMEA containing >4.0
equiv of THF contained exclusively (>95%) THF solvate 1.8
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The metalation and isomerization rates were monitored by following
the alkene and diene absorbances using a combination of in situ IR9 and 1H
NMR spectroscopies. Control experiments showed that DMEA and hexane
could be used interchangeably as cosolvents without detectable changes in
reactivity. The temperature for IR spectroscopy was controlled using baths
comprising ice/water (0 °C), dry ice/acetone (–78 °C), liquid
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nitrogen/methanol (–95 °C), and liquid nitrogen/Et2O (–116 °C). The
reproducibility of the latter two temperatures surprised us.
Rate studies were carried out at standard yet variable concentrations
of NaDA (0.025–0.40 M) and THF (1.00–12.3 M) in either DMEA or
hexane cosolvent, whereas the substrate concentrations were typically low
(0.0050 M) to maintain pseudo-first-order conditions. Non-linear least-
squares fits to the decays of the substrate afforded pseudo-first-order rate
constants (kobsd). The method of initial rates was used when pseudo-first-
order conditions were not rigorously established. Reactions with equimolar
base and substrate showed no evidence of autocatalysis or autoinhibition.
1-Pentene Isomerization. The metalation of 1-pentene with
NaDA/THF to provide pentenyl sodium is endothermic. Nonetheless, facile
isomerization of 1-pentene was observed in the presence of NaDA/THF at
25 °C via the presumed intermediacy of pentenyl sodium. Monitoring with
1H NMR spectroscopy showed an initial formation of 2-pentene as a 1:1
cis/trans mixture that slowly equilibrated to a 1:4 cis/trans mixture (eq 1; see
Figure 1). The proportions of cis- and trans-2-pentene at early conversion
were independent of THF and NaDA concentrations, confirming that both
are formed via isomeric transition states. Plots of the initial rates for the loss
of 1-pentene versus THF concentration (Figure 2) and NaDA concentration
(Figure 3) revealed first- and half-order dependencies, respectively. The
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overall rate law described by eq 2 is consistent with a trisolvated-monomer-
based transition structure, [A(THF)3]‡ (eqs 2 and 3; ‘A’ denotes a NaDA
subunit).10
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Figure 1. Plot of alkene concentration versus time measured with 1H NMR
spectroscopy for the isomerization of 0.76 M 1-pentene with 0.18 M NaDA
and 0.59 M diisopropylamine in 8.83 M THF/hexane at 25 °C. The traces
show 1-pentene (black), trans-2-pentene (blue), and cis-2-pentene (red) at
partial equilibration.
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0
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[THF] (M)
Figure 2. Plot of initial rates versus THF concentration for the isomerization
of 0.76 M 1-pentene (eq 1) with 0.18 M NaDA and 0.59 M
diisopropylamine in hexane cosolvent at 25 °C. The curve depicts an
unweighted least-squares fit to the function f(x) = ax + b: a = 0.168 ± 0.006;
b = 0.03 ± 0.03.
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[NaDA] (M)
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Figure 3. Plot of initial rates versus NaDA concentration for the
isomerization of 0.76 M 1-pentene (eq 1) with 0.59 M diisopropylamine in
3.93 M THF/hexane at 25 °C. The curve depicts an unweighted least-squares
fit to the function f(x) = axb: a = 19.2 ± 0.8; b = 0.67 ± 0.03. Covariance is
used because the NaDA titer was measured.
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–d[1-pentene]/dt = k[1-pentene][THF][A2(THF)4]1/2
(2)
1/2 A2(THF)4 + THF + 1-pentene
[A(THF)3·1-pentene]‡ (3)
The reaction coordinate for metalation was examined using density
functional theory (DFT) calculations at the B3LYP/6–31G(d) level of theory
with single-point MP2 calculations.11 Transition structures Z-2 and E-2,
affording cis- and trans-2-pentene, respectively, predicted a modest trans
selectivity (eq 4) that was not borne out experimentally. A distinct 
interaction between sodium and the developing allyl anion was visible in
both cases.12
Allyl Ether Isomerizations. NaDA-mediated metalations of allyloxy
ethers 3a–d are also endothermic, but the catalyzed isomerizations afforded
enol ethers 4a–d13 in synthetically useful >50:1 Z:E selectivities (eq 5).
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Analogously selective isomerizations have been reported by Williard and co-
workers14 using LDA/THF but are >1000-fold slower.15 Monitoring the
isomerization of allyl methyl ether with NaDA in THF at –116 °C revealed a
first-order THF dependence and half-order NaDA dependence (supporting
information), which implicated a trisolvated-monomer-based metalation (eqs
6 and 7). DFT computations showed a strong preference for transition
structure Z-5a relative to E-5a. Distinct methoxy–sodium interactions were
observed in lieu of the allyl–sodium interactions observed with simple
alkenes (eq 8). The energies were consistent with the Z selectivity.
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–d[3a]/dt = k[3a][THF][A2(THF)4]1/2
[A(THF)3·(3a)]‡
(6)
(7)
1/2 A2(THF)4 + THF + 3a
Trimethylsilyl groups are often suggested to suppress O–Li
interactions owing to a combination of steric and electronic effects,16 and the
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tert-butyldimethylsilyl moiety is larger. Of course, this conventional wisdom
gleaned largely from empirical evidence—even if true—may not apply to
organosodium reagents. In the event, the highly Z-selective isomerizations
(eq 5) occurred at the following approximate relative rates: R = methyl (1),
trimethylsilyl (10–1), tert-butyldimethylsilyl (10–2), and triisopropylsilyl (10–
4). Rate studies (supporting information) revealed that the trimethylsilyl
ether isomerized at –78 °C via monomer-based transition structure
[A(THF)3(3b)]‡, which is analogous to that for the isomerization of allyl
methyl ether; the high Z preference is reflected in eq 9. A small non-zero
intercept was consistent with [A(THF)2(3b)]‡. The tert-butyldimethylsilyl
ether isomerized at –78 °C and was shown kinetically to occur via a
disolvated monomer, [A(THF)2(3c)]‡ , while retaining a high Z preference
supported computationally (eq 10). Given that the loss of primary shell
solvation is typically endothermic by >5 kcal/mol, the rate reduction is
surprisingly muted. The triisopropylsilyl ether isomerized at 0 °C and was
shown kinetically to metalate via trisolvated monomer [A(THF)3(3d)]‡ while
retaining the Z selectivity observed experimentally and supported
computationally (eq 11). We return to the role of stereoelectronic control
and changing solvation numbers in the discussion.
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Isomerization of allyloxy-tert-butyldimethylsilane 3c using NaDA in
neat THF containing 3 equiv of (i-Pr)2N–D with monitoring by 1H NMR
spectroscopy showed <20% deuterium incorporation in Z-4c, indicating that
the proton transfer is intramolecular. The sequence in Scheme 2 is
computationally viable. The Na–N contact stretches to ~3.5 Å
computationally en route to Z-8c while the proton reorients toward the allyl
anion terminus.
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Scheme 2. Intramolecular proton transfer in allyloxy to enol ether
conversion.
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Isomerization: Catalysis. The isomerizations described above,
although carried out stoichiometrically in the rate studies, were inherently
catalytic in NaDA. The simplicity of a catalytic protocol is illustrated in eq
12. Treatment of neat allyloxytrimethylsilane with 6.5% NaDA monitored
with 1H NMR spectroscopy showed quantitative conversion to 4b in 30–60
seconds at room temperature. Compared with other protocols, this
preparation is a remarkably simple one for a useful synthon.14,17
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Allyloxy 1,4-Eliminations. The high Z selectivity for allyl ether
isomerization prompted us to examine substituted allyl ethers as putative
substrates, but 1,4-eliminations intervened (eqs 13 and 14) to the exclusion
of isomerization. The volatile alkenes in eq 13 were formed cleanly as
shown by 1H NMR spectroscopy. Myrcene (10) was isolated pure in
excellent yield.
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Diene Metalations. 1,4-Dienes are sufficiently acidic to metalate
exothermically with NaDA in THF (eq 15) and afford synthetically useful
dienyl sodiums at rates that outpace those of alternative deprotonations with
BuLi/TMEDA and LDA/THF. Monitoring the reaction of 1,4-
cyclohexadiene with NaDA in 2.0–10 M THF at –95 °C showed a loss of
substrate (1642 cm–1) and the formation of the cyclohexadienyl sodium
(1558 cm–1). The transformation was confirmed by trapping the resulting
sodium salt with TIPSCl.7 Rate studies using IR spectroscopy (supporting
information) showed a first-order dependence on diene, half-order
dependence on NaDA, and second-order dependence on THF (eq 16)
consistent with a tetrasolvated-monomer-based transition structure as
depicted in eq 17. Although the A(THF)4 fragment in isolation was
computationally viable, attempts to calculate 11 consistently led to the
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extrusion of a THF ligand, which afforded trisolvate 12 displaying a distinct
-allyl sodium interaction. Rate studies of the metalation of 1,4-pentadiene
revealed an entirely analogous [A(THF)4·(diene)]‡ stoichiometry and a -
bonded [A(THF)3·(diene)]‡ transition structure computationally (supporting
information). Attempted metalations of 1,3-cyclohexadiene appeared to
afford polymer under relatively forcing conditions (0 °C) as might be
expected.18
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–d[diene]/dt = k[diene][THF]2[A2(THF)4]1/2
[A(THF)4·(diene)]‡
(16)
(17)
1/2 A2(THF)4 + 2THF + diene
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Discussion
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The first paper in this series promulgated NaDA/DMEA as an easily
prepared, effective Brønsted base that compares favorably to LDA/THF.7 A
second paper described detailed structural studies of NaDA in various
standard coordinating solvents8 as a foundation for the current mechanistic
study and those that will follow. The temptation to rely on analogies of
sodium amides to lithium amides owing to decades of experience is fraught
with risk.19 Parallel behaviors of lithium and sodium do exist, but they are
imperfect and require experimental support. The mechanistic studies
described herein begin to examine the relationships among organosodium
aggregation, solvation, reactivity, mechanism, and selectivity.
The current study probed a combination of the synthetic utility and
underlying mechanism of NaDA/THF-mediated reactions of alkenes and
dienes. NaDA cleanly and rapidly metalates 1,4-dienes, whereas synthetic
chemists often resort to using potentially more destructive alkyllithiums.20,21
By contrast, metalations of simple alkenes and allyloxy ethers are
endothermic, yet facile isomerizations underscore synthetic opportunities
and provide an opportunity to study fundamental principles of sodium
coordination chemistry.
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Diene Metalation. NaDA metalates 1,4-cyclohexadiene and 1,4-
pentadiene to form dienylsodiums rapidly and quantitatively. Both react via
tetrasolvated monomers; transition structure 11 is emblematic. 1,4-
Cyclohexadiene reacts approximately 10-fold slower than 1,4-pentadiene,
presumably owing to unproductive substituents as well as the suboptimal
alignment of the C–H bond with the  system. Tetrasolvation in the rate-
limiting transition structures contrasts with the trisolvation observed with
alkene isomerizations.
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The synergies of kinetics and computations offer excellent
opportunities to test theory–experiment correlations, which is crucial for our
fledgling studies of sodium amides. In this case, however, the correlation
proved imperfect: all attempts to find tetrasolvated transition structure 11
afforded trisolvate 12, which resulted from the extrusion of a THF ligand
with the formation of a -allyl sodium interaction. It is plausible that the
transition structure includes four solvents (demonstrated kinetically) and the
 interaction predicted computationally. DFT often fails to replicate highly
solvated lithiums.22
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1-Pentene Isomerization. Despite the inherent endothermicity of
alkene metalations, mechanistic details were obtained from studies of the
isomerization of 1-pentene to cis- and trans-2-pentenes (eq 1). The kinetic
formation of both stereoisomers in equal proportions is followed by a slower
stereochemical equilibration (Figure 1). Rate studies showing trisolvated-
monomer-based transition structures are supported by computational studies
showing Z-2 and E-2 transition structures manifesting distinct -allyl
sodium interactions. A predicted kinetic preference for E-2 is not observed
experimentally. As noted by a referee, the results seem to be at odds with
thermodynamic preferences for the Z allyl sodiums,24c but that is not
surprising for kinetic versus thermodynamic control. The observed
equilibration, of course, is for the alkenes rather than the allyl sodiums.
Allyloxy Isomerizations: Mechanistic Chameleons. The series of
NaDA/THF-mediated allyl ether (CH2=CHCH2OR) isomerizations (eq 5)
constitutes the most interesting portion of this study both synthetically23 and
mechanistically. Rates of isomerization correlate with apparent steric effects
following the order R = Me > SiMe3 > Si(t-Bu)Me2 > Si(i-Pr)3. The
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underlying mechanistic differences, however, are far more nuanced (eqs 8–
11). Methyl and SiMe3 moieties are essentially interchangeable, reacting via
a trisolvated-monomer-based transition structure depicted generically as A‡
with prominent Na–O interactions to the exclusion of Na–C -allyl contacts.
The decidedly larger Si(t-Bu)Me2 group metalates significantly more slowly
via a disolvated monomer, B‡, while retaining the putative Na–O contact.
The notoriously large Si(i-Pr)3 (TIPS) moiety blocks the Na–O contact,
replacing it with an Na–C -allyl interaction, which allows it to return to a
trisolvated monomer (C‡).
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Scheme 3 offers an alternative perspective on the interplay among
allyloxy RO–Na coordination, steric bulk, and solvation number. We have
taken the liberty of normalizing the energies of the reactants to a common
level. Transition structures A‡, B‡, and C‡ are color-coded. Moving from left
to right reflects increasing steric demand and decreasing relative rate
constants (krel). The energy of A‡, which is stabilized by both trisolvation
and a Na–O contact with the allyloxy fragment, is sterically sensitive. The
intermediate steric demand of the Si(t-Bu)Me2 moiety sacrifices a stabilizing
Na–THF interaction to retain the Na–O contact with the allyloxy. In the
limit of high steric demand, the Na–O contact is inaccessible, which reveals
the inferior Na–C contact (C‡) while returning to trisolvation. Transition
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structure C‡ is insensitive to the steric demands of the R group, which make
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it dominant by default for the TIPS ether.
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Scheme 3. Qualitative barriers for the isomerization of allyloxy ethers via
differing transition structures.
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Allyloxy Isomerization: Origin of Z Selectivity. The contrasteric
isomerization of allyl ethers to provide Z-(1-propenyl) ethers (eq 5) tempts
us to invoke a privileged role for NaDA in this transformation, but Z-
selective isomerizations have been noted with t-BuOK/DMSO17 and
LDA/THF.14 An overlay of the computed pro-Z and pro-E transition
structures (Z-5 and E-5, respectively) reveals complete superposition of the
A(THF)3 fragment, with the sole distinction being the terminal methylene
orientation. Given that transition states 5a–d are product-like in accord with
the Hammond postulate, we directed our attention toward stereoelectronic
preferences endemic to the putative allylsodium intermediate. Geometric
preferences within this class of allyl anions have been addressed both
experimentally24 and computationally.25 Compared with E-11, Z-11 shows a
greater spatial overlap—and consequent stabilization—of the allyl anion π
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manifold with the O–R σ* orbital. The transition-state energy differences
cited in eqs 8–11 are reflected in the calculated relative energies of allyl
anions Z-13 and E-13 and are consistent with this highly simplified, purely
stereoelectronic model.26
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Conclusion
NaDA/THF observably metalates dienes and transiently metalates
alkenes and allyloxy ethers. The NaDA-mediated isomerization of 1-pentene
shows no stereoselectivity. By contrast, the >50:1 Z-selective isomerization
of allyl ethers is synthetically noteworthy. Rate and computational data
revealed the roles of solvation and aggregation, which are key for
understanding organosodium coordination chemistry. The current
investigation reinforces our enthusiasm for NaDA to effect difficult
metalations that plague synthetic chemists. That it can be prepared as stock
solutions in trialkylamines in minutes using standard glassware and stored
for months with refrigeration amplifies its appeal.7
Experimental
Reagents. NaDA was prepared from diisopropylamine, isoprene, and
sodium dispersion by using a modified7 procedure first reported by
Wakefield.3a Despite little evidence of improved efficacy, NaDA was
crystallized from DMEA/hexane as an added measure.8 THF, hexane, and
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DMEA were vacuum-transferred from purple solutions of sodium
benzophenone ketyl. Air- and moisture-sensitive materials were manipulated
under argon using standard glovebox, vacuum line, and syringe techniques.
The substrates were commercially available or prepared with standard
protocols.27
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IR Spectroscopic Analyses. IR spectra were recorded using an in situ
IR spectrometer fitted with a 30-bounce, silicon-tipped probe. The spectra
were acquired in 16 scans at a gain of 1 and a resolution of 4 cm–1. A
representative reaction was carried out as follows: The IR probe was inserted
through a nylon adapter and O-ring seal into an oven-dried, cylindrical flask
fitted with a magnetic stir bar and a T-joint. The T-joint was capped with a
septum for injections and a nitrogen line. After evacuation under full
vacuum, heating, and flushing with nitrogen, the flask was charged with
NaDA (62 mg, 0.50 mmol) in THF/DMEA (4.9 mL) and cooled in a dry
ice–acetone bath prepared with fresh acetone. After a background spectrum
was recorded, ether 3b (0.050 mmol) was added with stirring. For the most
rapid reactions, IR spectra were recorded every 6 s with monitoring of the
absorbance at 1510 cm–1 over the course of the reaction.
NMR Spectroscopy. All samples for reaction monitoring and
structure elucidation were prepared using stock solutions and sealed under
partial vacuum. Standard 1H and 13C NMR spectra were recorded at 500 and
125.79 MHz, respectively.
Myrcene (10). To a stirred solution of NaDA (500 mg, 4.06 mmol) in
THF (15 mL) at –78 °C was added geraniol trimethylsilyl ether 9 (836 mg,
3.70 mmol). After 5 h at –78 °C, the reaction was quenched with water and
partitioned between water and pentane. The crude extract was
chromatographed on silica with pentane (Rf = 0.5) and the fractions were
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concentrated to afford myrcene (428 mg, 85% yield) identical to that
reported in the literature (1H and 13C NMR).28
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Enol ether 4b: neat isomerization. To a NMR tube charged with
solid NaDA (71 mg, 0.58 mmol) was added neat allyloxytrimethylsilane (1.5
mL, 8.9 mmol) at room temperature. After 1 minute, the crude reaction
mixture was vacuum-transferred to a receiving flask cooled with dry ice–
acetone to provide 0.982 g (84% yield) of product enol ether 4b
contaminated by ~5% diisopropylamine.
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Acknowledgments. We thank the National Institutes of Health
(GM039764) for support.
Supporting Information: Spectroscopic, kinetic, and computational
data and authors for reference 11. This material is available free of charge
via the Internet at http://pubs.acs.org.
Author Information
David B. Collum
*dbc6@cornell.edu
Notes
The authors declare no competing financial interests.
References and Footnotes
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Organomet. Chem. 1979, 179, 123. (d) Lochmann, L.; Pospíšil, J.; Lím, D.
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6. For an interesting historical perspective on organoalkali metal chemistry,
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7. Ma, Y.; Algera, R. F.; Collum, D. B. J. Org. Chem. 2016, 81, 11312.
8. Algera, R. F.; Ma, Y.; Collum, D. B. J. Am. Chem. Soc. 2017, 139, 7921.
9. (a) Rein, A. J.; Donahue, S. M.; Pavlosky, M. A. Curr. Opin. Drug
Discov. Dev. 2000, 3, 734. (b) Connolly, T. J.; Hansen, E. C.; MacEwan, M.
F. Org. Process Res. Dev. 2010, 14, 466.
10. The rate law provides the stoichiometry of the transition structure
relative to that of the reactants: Edwards, J. O.; Greene, E. F.; Ross, J. J.
Chem. Educ. 1968, 45, 381.
11. Frisch, M. J.; et al. GaussianVersion 3.09; revision A.1; Gaussian, Inc.:
Wallingford, CT, 2009.
12. Haeffner, F.; Houk, K. N.; Schulze, S. M.; Lee, J. K. J. Org. Chem.
2003, 68, 2310.
13. (a) Compound 4a: Leung, D. H.; Bergman, R. G.; Raymond, K. N. J.
Am. Chem. Soc. 2007, 129, 2746; (b) Compound 4b: Heathcock, C. H.;
Buse, C. T.; Kleschick, W. A.; Pirrung, M. C.; Sohn, J. E.; Lampe, J. J. Org.
Chem. 1980, 45, 1066; (c) Compound 4c: Su, C.; Williard, P. G. Org. Lett.
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2010, 12, 5378.; (d) Compound 4d: Guha, S. K.; Shibayama, A.; Abe, D.;
Sakaguchi, M.; Ukaji, Y.; Inomata, K. Bull. Chem. Soc. Jpn. 2004, 77, 2147.
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14. Su, C.; Williard, P. G. Org. Lett. 2010, 12, 5378.
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15. The acceleration was estimated assuming a factor 2 per 10 °C with the
adjustment for the relative rates. This is likely to be an underestimate.
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21. It appears to be unreported, but 1,4-dienes can be metalated with LDA.
Literature procedures use alkyllithiums.17
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22. Reyes-Rodríguez, G. J.; Algera, R. F.; Collum, D. B. J. Am. Chem. Soc.
2017, 139, 1233.
23. Stereocontrolled silyl enol ethers are synthetically important: (a)
Denmark, S. E. and Ghosh, S. K. Angew. Chem., Int. Ed. 2001 40, 4759. (b)
Lim, S. M.; Hill, N.; Myers, A. G. J. Am. Chem. Soc. 2009, 131, 5763. (c)
Wang, X.; Meng, Q.; Nation, A. J.; Leighton, J. L J. Am. Chem. Soc. 2002,
124, 10672. (d) Schumacher, R.; Reissig, H. U. Synlett 1996, 1121.
24. (a) Taskinen, E. J. Chem. Soc., Perkin Trans. 2 2001, 1824. (b) Bank, S.;
Schriesheim, A.; Rowe, C. A. J. Am. Chem. Soc. 1965, 87, 3244. (c) Haag,
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Tetrahedron 1977, 33, 2497.
26. This stereoelectronic model rationalizes the outcome of 1-pentene
isomerization, for which poorer overlap of the allyl anion π manifold with
C–H(C) σ* results in minimal disproportionate stabilization and consequent
stereorandom isomerization.)
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27. De Carvalho, M. E.; Meunier, B. Nouv. J. Chim. 1986, 10, 223.
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28. Myrcene is commercially available with 1H and 13C NMR spectra
reported by Sigma-Aldrich.
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