γ-Silylated α,ss-unsaturated amides - Preparation by [1,5]-sigmatropic rearrangement and use as masked dienolate equivalents in carbonyl condensations

Article abstract of DOI:10.1139/V09-054

The reaction of lithium dienolates derived from N,N-dialkylsenecioamides (1a-1c) with triorganosilyl electrophiles occurs initially at the oxygen atom predominantly, and is followed by an O → C silicon migration to afford the γ-silylated senecioamides (4a-4h). The γ-silylated senecioamide Z-4a undergoes fluoride-ion-mediated condensations with aromatic aldehydes to give kinetic α-(6) and thermodynamic γ-(5) condensation product patterns comparable to lithium dienolates. The TiCl₄-mediated reactions with aldehydes gives a-products (6) in a highly syn-selective manner. Possible transitionstate models for the syn-selective condensations are discussed and a chair-like transition state featuring bidentate coordination to titanium (11) is proposed.

Full text of DOI:10.1139/V09-054

745
g-Silylated a,b-unsaturated amides — Preparation
by [1,5]-sigmatropic rearrangement and use as
masked dienolate equivalents in carbonyl
condensations1
James R. Green, Babajide I. Alo, Marek Majewski, and Victor Snieckus
Abstract: The reaction of lithium dienolates derived from N,N-dialkylsenecioamides (1a–1c) with triorganosilyl electrophiles
occurs initially at the oxygen atom predominantly, and is followed by an O ? C silicon migration to afford the g-silylated
senecioamides (4a–4h). The g-silylated senecioamide Z-4a undergoes fluoride-ion-mediated condensations with aromatic
aldehydes to give kinetic a-(6) and thermodynamic g-(5) condensation product patterns comparable to lithium dienolates.
The TiCl4-mediated reactions with aldehydes gives a-products (6) in a highly syn-selective manner. Possible transition-
state models for the syn-selective condensations are discussed and a chair-like transition state featuring bidentate coordina-
tion to titanium (11) is proposed.
Key words: silicon migration, amide dienolate, allylsilane, Hosomi–Sakurai reaction, stereoselective.
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Resume : La reaction des dienolates de lithium derives des N,N-dialkylsenecioamides (1a–1c) avec des electrophiles
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triorganosilyles se produit dans un premier temps par le biais de l’atome d’oxygene et l’intermediaire subit une migration
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O ? C de l’atome de silicium qui conduit eventuellement aux senecioamides g-silyles (4a–4h). Le senecioamide g-silyle
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Z-4a donne des reactions de condensation avec les aldehydes aromatiques, catalysees par l’ion fluorure, qui conduisent a
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la formation des produits de condensation cinetique, a-(6), et thermodynamique, g-(5) avec des patrons similaires a ceux
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observes pour les dienolates de lithium. Les reactions des aldehydes, catalysees par le TiCl4, conduisent aux produits a-(6)
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avec une haute selectivite syn. On discute de divers modeles d’etats de transition qui pourraient expliquer la selectivite
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syn des condensations et on suggere que la meilleure explication est un etat de transition en forme de chaise comportant
une coordination bidentate vers le titane (11).
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Mots-cles : migration du silicium, dienolate amide, allylsilane, reaction de Hosomi–Sakurai, stereoselective.
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[Traduit par la Redaction]
demonstrated that dienolates derived from esters undergo ki-
netic O-silylation to give vinyl ketene O,O-acetals,5 which
then experience a [1,5]-sigmatropic O ? C silicon migration
to g-silylated products. An analogous migration has been
observed in b-pyrrolidino vinyl ketene O,N-acetals,6 and
O ? C or C ? O silicon migrations have been observed
on related systems,7–9 for many cases after our initial re-
port in this area.10 These combined results prompted the
present systematic study on tertiary amide dienolate silyla-
tion and the potential rearrangement of the resulting vinyl
ketene N,O-acetals to g-silylated a,b-unsaturated amides
(Scheme 1).
An additional incentive for the present study was the
consideration that, with few exceptions, the reactivity of g-
silylated alkenoic acid derivatives has been restricted to elec-
trophilic cyclizations on alkenes and epoxides.11,12 Given the
rich chemistry of allylsilanes,13 such g-silylated carbonyl
compounds may be considered as storable dienolate
equivalents. This is particularly relevant in the 3-methyl-2-
butenamide (senecioamide) case, as the lithio dienolates
give modest to poor a- kinetic aldol selectivity. Conse-
quently, we set as a goal to test the functionalized allylsilane
dienolate equivalent in fluoride- and Lewis acid mediated
aldol chemistry to provide a contribution to the area of
diastereoselective C–C bond formation.10,14 The results of
Introduction
From the considerable body of literature on dienolates de-
rived from a,b-unsaturated acid derivatives,2 including our
work on a,b-unsaturated amides,3 a clear pattern of reactivity
has emerged, especially for carbon-based electrophiles. In
the absence of additional heteroatom substitution, predomi-
nant to exclusive a-carbonyl substitution is observed, with
preferential g-substitution products arising under thermody-
namic conditions. Conversely, the seminal work of Casey4
Received 21 January 2009. Accepted 31 March 2009. Published
on the NRC Research Press Web site at canjchem.nrc.ca on
2 June 2009.
J.R. Green.1 Department of Chemistry, University of Windsor,
Windsor, ON N9B 3P4, Canada.
B.I. Alo. Department of Chemistry, University of Lagos, Akoka,
Lagos, Nigeria.
M. Majewski. Department of Chemistry, University of
Saskatchewan, Saskatoon, SK S7N 5C9, Canada.
V. Snieckus.2,3 Department of Chemistry, University of
Waterloo, Waterloo, ON N21 3G1, Canada.
1Corresponding author (e-mail: jgreen@uwindsor.ca).
2Corresponding author (e-mail: snieckus@queensu.ca).
3Present address: Department of Chemistry, Queen’s University,
Kingston, ON K7L 3N6, Canada.
Can. J. Chem. 87: 745–759 (2009)
doi:10.1139/V09-054
Published by NRC Research Press

746
Can. J. Chem. Vol. 87, 2009
Scheme 1. Reagents and conditions: (a) Me3SiCl; (b) D, THF.
Scheme 2. Reagents and conditions: (a) (i) LDA, THF, –78 8C; (ii) R13 SiCl, –78 8C to RT; (b) THF, D.
Table 1. g-Silylation results for senecioamides 1a, 1b, and 1c.
Scheme 3. Reagents and conditions: (a) DMAD, benzene, 0 8C.
Entry
R31
R2
Product
4a
4b
4c
4d
4e
4f
4g
4h
Yield (%)
Z:E
91:9
1
2
3
4
5
6
7
8
Me3
Et3
i-Pr3
MePh2
Me3
Et3
Me
Me
Me
Me
Et
Et
i-Pr
i-Pr
75
74
35
92a
74
67
65
92a
77:23
63:37
36:64
53:47
31:69
35:65
59:41
Me3
MePh2
our studies concerning lithium dienolates derived from N,N-
dialkylsenecioamides and their g-silylated reaction products
are presented herein.
aThe THF at reflux step was not carried out.
Enolate silylation and silicon migration
reactions of senecioamides
trimethylsilylated-2-butenamides, Z-4a and E-4a, in 74%
and 2% yields, respectively. The stereochemistry of the two
1
compounds was determined on the basis of the downfield H
N,N,3-Trimethyl-2-butenamide
(N,N-dimethylsenecioa-
NMR chemical shifts of the protons g and cis to the amide
function relative to those g and trans to the carbonyl, and
the expected aromatic solvent induced shift (ASIS)16 of the
mide) (1a) was deprotonated with LDA under the estab-
lished conditions,3a and the resultant dienolate underwent
silylation with Me3SiCl to afford the vinylketene O,N-acetal
(2a) (Scheme 2). Compound 2a was found not to be stable
to an aqueous workup or chromatographic purification, but
1
g,cis- and g,trans-protons observed in their H NMR spectra
in C6D6 (Scheme 2).
1
The basic protocol outlined above was extended to other
chlorosilanes (chlorotriethylsilane, chlorotriisopropylsilane,
and chloromethyldiphenylsilane) and other senecioamides
(1b, 1c), and the combined results are presented in Table 1.
For reaction of the dienolates with MePh2SiCl, C-silylation
did not require the heating-to-reflux step, and it was there-
fore omitted in these cases (Table 1, entries 4 and 8). In the
isolated g-silylated products (4) other than 4a, the most
noteworthy feature was the increased relative amounts of
was identified by H NMR spectroscopy; its characterization
as the Z-isomer was supported by NOE difference experi-
ments showing an enhancement of the vinyl CH resonance
(d 4.48) upon irradiation of the N-substituted methyl
resonances (d 2.26).15 Furthermore, 2a was trapped by
Diels–Alder reaction with dimethyl acetylene dicarboxylate
to give the phthalate ester 3 in low yield (Scheme 3) (see
Supplementary data).8 In normal practice, however, 2a was
heated at reflux in THF for 18 h to afford two isomeric 4-
Published by NRC Research Press

Green et al.
747
Scheme 4. Reagents and conditions: (a) R13SiCl, –78 8C to RT; (b)
THF, D.
Scheme 5. Reagents and conditions: (a) THF, D, 19h.
at –78 8C with Et3SiCl and Me3SiCl, respectively, and, after
warming to room temperature, the respective solutions of
the two reactions were mixed in a 1:1 ratio and heated to
reflux (19 h). Analytical HPLC of the resultant mixture
revealed the presence of g-silylation products Z-4b, E-4b,
Z-4e, and E-4e, but not crossover products Z-4a, E-4a,
Z-4f, or E-4f (Scheme 5) (see Supplementary data).8 This
constitutes strong evidence for the intramolecular nature of
the [1,5]-silicon migrations of these silylated vinylketene
O,N-acetals.
With a facile method for generating g-silylated-a,b-
unsaturated amides in hand, attention was turned to the con-
densation chemistry of these compounds. Since Z-4a was
obtained with the highest stereoselectivity and possesses the
most widely employed silyl group, the reactivity of this
compound with carbonyl derivatives was pursued. As de-
scribed below, fluoride- and Lewis acid mediated condensa-
tion reactions were investigated.
the E-isomer to the point where the E-isomer predominated
in several instances (Table 1, entries 4, 6, and 7).
To further clarify the source of the g,E-isomer silylation
products, the reaction of the dienolate of 1a with Et3SiCl
was examined more closely prior to the reflux step by sub-
jecting an aliquot of the product to an anhydrous workup
and the remainder to a conventional aqueous workup. For
the former aliquot, integration of the respective vinyl proton
Fluoride-mediated condensations of Z-4a
1
resonances in the H NMR spectrum showed a 23:77 ratio
for g-silylated products (Z- + E-4b) and the ketene O,N-acetal
(2b). Conversely, the material subjected to aqueous workup
gave Z-4b and E-4b in 4% and 16% yields, respectively.
Comparing this to entry 2 in Table 1 (Z-4b, 58%; E-4b,
18%), it is apparent that most of the g,Z-silylated product
arose from the O- to C-[1,5]-silicon migration of the
vinylketene O,N-acetal (2b), whereas the corresponding
g,E-silylated product most likely resulted from direct attack
on the dienolate (Scheme 4). In the cases with MePh2SiCl
as the electrophile, it is likely that both isomers of g-
silylation products result from direct silylation, in keeping
with the relatively greater HSAB ‘‘softness’’ of MePh2SiCl,17
and in the fact that 2d and 2h are not actually formed in sig-
nificant amounts.
The variation of E/Z ratios in these g-silylated amides is
worthy of further comment. In the N,N-dimethyl amide
series, increasing amounts of E-isomers may reflect increas-
ing direct g-silylation due to a greater reactivity with bulkier
chlorotrialkylsilanes when the dienolate is in the s-trans
form. This proposal breaks down for the N,N-diisopropyl
amide series, as MePh2SiCl undergoes reaction by direct g-
attack and yet gives predominantly Z-4h. The regiochemis-
try for direct g-attack is clearly a more complex process in
these cases.
The reaction of Z-4a with benzaldehyde was induced by
subjecting its THF solution to a catalytic amount of n-Bu4NF
(5 mol%) at RT to afford a mixture of g-hydroxyalkylated
compounds Z-5a and E-5a in 58% and 14% yields, respec-
tively (Scheme 6). This process was extended to other aro-
matic aldehydes, and gave some interesting differences in
the reaction products (Table 2). Aromatic aldehydes bearing
strong electron-withdrawing groups (EWGs) gave mixtures
of g-(5) and a-hydroxyalkylation products (6) (Table 2,
entries 4 and 5); conversely, substrates not possessing these
EWGs gave only g-hydroxyalkylated products (Table 2,
entries 1–3). Reaction with benzophenone resulted in the
formation of the g-condensation products, but unless the re-
action was performed at low temperature (–45 8C), these
underwent elimination to give 7 (Table 2, entries 6 and 7).
By contrast, attempted reaction with aliphatic aldehydes re-
sulted in desilylation of Z-4a and isolation of only trace
amounts of condensation products.
These condensations, if effected at lower temperatures
(–45 8C) for short periods of time, required the use of
stoichiometric amounts of fluoride ion. Under such condi-
tions, however, a-condensation products predominated as
separable syn/anti diastereomeric mixtures, together with
small amounts of the g,Z-condensation products (Scheme 6,
Table 3).
To establish the inter- or intra-molecularity of the [1,5]-
silicon migration, a crossover experiment was performed.
The lithium dienolates of 1a and 1b were allowed to react
The identities of the condensation products were readily
1
established from their H NMR spectra. The a-products (6)
Published by NRC Research Press

748
Can. J. Chem. Vol. 87, 2009
Scheme 6. Reagents and conditions: (a) (i) ArCRO, 5 mol% n-BuNF, THF, –78 8C to RT; (ii) NH4Cl(aq); (b) (i) ArCHO, 100 mol%
n-BuNF, THF, –45 8C, 2 min; (ii) NH4Cl(aq)
.
Table 2. Fluoride-catalyzed condensations of Z-4a with aromatic aldehydes and benzophenone.
Entry
ArCRO
PhCHO
3,4-(MeO)2 C6H3CHO
Pyridine-3-CHO
Pyridine-4-CHO
4-O2NC6H4CHO
Ph2COa
g-Product
5a
5b
5c
Yield (%), (Z:E)
72, (80:20)
75, (65:35)
70, (81:19)
42, (100:0)
31, (100:0)
68, (30:70)
29, (33:67)
a-Product
Yield (%), (syn:anti)
—
—
—
37 (56:44)
48 (45:55)
—
1
2
3
4
5
6
7
5d
5e
6d
6e
5g, 5fb
7
Ph2CO
—
aReaction conducted at –45 8C.
bIsolated as the trimethylsilyl ether.
Fig. 1. Stereochemical assignments of aldol adducts.
Table 3. Low-temperature stoichiometric fluoride-mediated
condensations of Z-4a with aromatic aldehydes.
a- (%),
Entry
ArCHO
a-Product
(syn:anti)
g- (%)
1
2
3
4
PhCHO
6a
6b
6d
6e
64, (48:52)
52, (48:52)
61, (44:56) 13
57, (45:55) 30
6
6
3,4-(MeO)2 C6H3CHO
Pyridine-4-CHO
4-O2NC6H4CHO
were distinguished by virtue of the larger vicinal coupling
constant of the a-methine proton in the anti-diastereomer (J =
6–7 Hz) relative to the syn-diastereomer (J = 4–5 Hz).18
The Z- and E-isomers of the g-condensation products (5)
were most readily discriminated by the downfield ASIS of
the allylic methyl groups of the Z-isomers, versus the up-
field ASIS of the corresponding group in the E-isomers
(Fig. 1).
The observation of predominant a-condensation products at
low temperatures and short reaction times but g-condensation
products at higher temperatures and longer reaction times is
a clear kinetic (a-) versus thermodynamic (g-) product
control situation similar to that observed for analogous
lithium dienolate condensation chemistry.3a In the cases of
4-nitrobenzaldehyde and pyridine-4-carboxaldehyde, the
EWGs render the initial kinetic condensation favourable to
such a degree that reversibility is suppressed completely
(4-nitrobenzaldehyde) or partially (pyridine-4-carboxaldehyde).
We note that the amount of g-product with 4-nitrobenzaldehyde
under kinetic conditions is relatively high, although it is still
the minor product. We attribute the nearly non-existent dia-
stereoselectivity of the a-condensation in all cases to the re-
Published by NRC Research Press

Green et al.
749
Scheme 7. Competitive transition states for kinetic fluoride-mediated condensations
Scheme 8. Reagents and conditions: (a) (i) R1R2CO, TiCl4, CH2Cl2, RT; (ii) NH4Cl(aq)
.
Table 4. TiCl4-mediated condensations of 4a with aldehydes and
benzophenone.
in obtaining condensation products stereoselectively. The
use of a monodentate Lewis acid (BF3ꢀOEt2) and benzalde-
hyde under otherwise identical conditions resulted only in
minimal conversion (<10%) of Z-4a to syn-6a; even ex-
cesses of BF3ꢀOEt2 (4.4 equiv.) and PhCHO (4.8 equiv.)
afforded syn-6a in only 7% yield (see Supplementary data).
Similarly, allylsilane E-4a was much less reactive than Z-4a
under identical conditions. Even at higher temperature, at-
tempted reaction of E-4a with benzaldehyde in the presence
of TiCl4 resulted mainly in the isolation of recovered start-
ing material, along with only trace amounts of condensation
product syn-6a and desilylation product 10a (see Supple-
mentary data). In the alternative obvious approach,20 reac-
tion of the lithium dienolate of 1a with TiCl4, followed by
treatment with benzaldehyde, resulted only in the formation
of oligomeric materials (see Supplementary data).
The observed high syn diastereoselectivity in the TiCl4-
mediated reactions of Z-4a with aromatic and linear
aliphatic aldehydes is striking, particularly in light of the
related condensation reactions of g-stannyl- and g-
germylsenecioic ‘‘esters’’ reported by Yamamoto21 and
Hudlicky,22 and indium-mediated Reformatsky reactions of
g-bromocrotonates,23 which generally show high anti
diastereoselectivity.24 While experimentally the results are
nicely complementary, clearly our results cannot be ration-
alized in terms of an acyclic transition state with an anti-
periplanar relationship between the allylsilane and
aldehyde functions, as advanced by Yamamoto.25 A more
plausible explanation is based on the ability for bidentate
coordination to TiCl4, and the greater basicity of the amide
relative to the ester function.26 Working on the assumption
that the predominant s-cis-conformation of the unsaturated
tertiary amide27 is maintained, we envisage a cyclic transi-
tion state featuring coordination of both the amide and al-
dehyde carbonyls to Ti, with the allylsilane function
positioned in an exocylic mode. Formulating this transition
state as a chair, with the aldehyde R group pseudoequato-
rial and a synclinal orientation of the allylsilane and
aldehyde (11), allows rationalization of the observed syn-
Entry R1R2CO
a-Product
Yield
62
73
64
68
syn:anti
>97 : <3
97:3
1
2
3
4
5
6
PhCHO
6a
6e
6h
6i
6j
6g
4-O2NC6H4CHO
n-PrCHO
i-PrCHO
EtCHO
96:4
59:41
87:13
—
52
72
Ph2CO
action proceeding via the nearly equal in energy acyclic
transition states 8 and 9 (Scheme 7). While the pattern of
reactivity is consistent with a reaction proceeding via a free
enolate, we do not consider this as an unambiguous proof.
Attempts to induce fluoride-ion-catalyzed reactions of silyl
ketene acetal (2a) with benzaldehyde afforded only hydroly-
sis products.19
TiCl4-mediated condensations of Z-4a with
aromatic and aliphatic aldehydes and
benzophenone
The condensation reaction of the g-silylated amide Z-4a
with benzaldehyde could also be initiated by a Mukaiyama-
type process, often referred to as the Hosomi–Sakurai
reaction,14d in the presence of stoichiometric amounts of
TiCl4 under mild conditions. The condensation was found
to occur with exclusive a selectivity and nearly complete syn-
diastereoselectivity to give product 6a in reasonable yield
(Scheme 8, Table 4). This process was extended to other ar-
omatic and aliphatic aldehydes (6e–6j), with some caveats:
aldehydes with Lewis basic sites (4-methoxybenzaldehyde
and 3,4-dimethoxybenzaldehyde) gave only desilylation,
without condensation, while branched aliphatic aldehyde
(2-methylpropanal) gave much lower levels of diastereose-
lection (syn/anti 6h = 59:41).
Alteration of this basic protocol was much less successful
Published by NRC Research Press

750
Can. J. Chem. Vol. 87, 2009
Scheme 9.
diastereomeric product (Scheme 9).28 Formation of the anti-
diastereomer would require either a pseudoaxial aldehyde R
group (12), or boat transition state (13). In context of this
proposal, the analogous TiCl4-mediated condensations of
g-stannyl-/germyl-senecioic esters21,22 lead to reduced
anti-diastereoselection, which may indicate destructive
competition of analogous bidentate coordination in these
cases. In addition, it has been demonstrated that chiral sen-
ecioyl oxazolidinones undergo n-Bu2BOTf-mediated reac-
tions with aldehydes with high syn-selectivity and high
diastereofacial selectivity.29 For esters, however, the selec-
tivity profile appears complementary to our work in that
there is an apparent requirement for branching in aliphatic
aldehydes to achieve high diastereoselectivity.30
The greater reactivity of Z-4a relative to E-4a may be ra-
tionalized in two possible ways. In a chair transition state
for Z-4a, the depicted orientation (14) of the C–Si bond sug-
gests potential intramolecular transfer of an apically ligated
chloride to a syn-oriented silicon (Scheme 10), an analogous
possibility does not exist for E-4a. This possibility has been
advanced on occasion in Hosomi–Sakurai reactions,10,31 and
in silyl ketene acetal-aldehyde and allylsilane-enone conden-
sation chemistry,32 and has received computational support
at the DFT level.33 In contrast, careful experiments on intra-
molecular condensations of aldehydes with chiral allylsi-
lanes and allylstannanes are not consistent with the
stereochemical outcome for such a syn-SE0 orientation.34
The alternate plausible source of the greater reactivity of
Z-4a stems from the possibility of a stabilizing secondary
orbital overlap of the allylsilane (HOMO) with the aldehyde
(LUMO) (15), which would not be available in the reaction
path of E-4a. Originally proposed for aldol condensation
chemistry,35 this rationalization has been invoked in support
of synclinal orientations in allylstannane-aldehyde condensa-
tions,28d,36 and should, in principle, be capable of extension
to Lewis acid mediated allylsilane-aldehyde condensations.
Pursuant to this question, transition states approximating
14 and 15 were calculated at the DFT level. An ‘‘outside’’
trimethylsilyl transition state corresponding to 11/15 was lo-
Scheme 10.
cated (16, Scheme 11); it features a relatively short forming
bond (1.81 A), a significantly lengthened senecioamide C4–
Si bond (2.00 A), and nearly equal amide C2–C3 and C3–
C4 bonds (1.44 and 1.44 A). Furthermore, a senecioamide
˚
˚
˚
˚
C4 – aldehyde oxygen distance (3.17 A) shorter than the
sum of the van der Waals radii is found, consistent with a
weak bonding interaction between the two atoms. In con-
trast, an ‘‘inside’’ trimethylsilyl transition state correspond-
ing to 14 was found to be 2.9 kcal mol–1 higher in energy
˚
(17). The nearest Cl–Si contact (3.85 A) is larger than the
sum of the van der Waals radii. Consequently, the intramo-
lecular transfer of chloride transition state 14 is not sup-
ported in our system at this level of calculation.
In summary, we have shown that g-silylated senecioa-
mides 4a–4h are easily obtained by [1,5] O?C silicon mi-
gration or direct silylation of the corresponding enolates,
depending upon the softness of silyl groups. The isomeric
g-(Z)-silylsenecioamides Z-4a – Z-4c, Z-4e – Z-4g are ob-
tained by the O?C silicon migration but also are formed
from the direct silylation reactions, whereas the correspond-
ing E-isomers are exclusively or near-exclusively formed
from the direct silylation process. The simplest g-silylse-
neciomamide serves as a stable and easily stored (>1 year
at –20 8C) senecioamide dienolate equivalent. Fluoride-
catalyzed reactivity of Z-4a with aromatic aldehydes or
Published by NRC Research Press

Green et al.
751
Scheme 11. DFT-minimized transition states of 15, 14, R = CH3.
benzophenone shows product patterns analogous to those
(s: singlet, d: doublet, t: triplet, q: quartet, sept: septet, m:
multiplet, br: broad), coupling constant (J, Hz), number of
protons; assignment. Low-resolution mass spectra were de-
termined on a VG 7070F instrument at 20 eV unless other-
wise stated. High-resolution mass spectra were determined
on a VG ZAB-E spectrometer. Analytical gas chromatogra-
phy (GC) was performed on either a Hewlett Packard 5840
A instrument or a Varian 6500 instrument using commer-
cially available 10% SE-30 packed or capillary columns,
respectively. Analytical thin layer chromatography (TLC)
was performed using Merck precoated silica gel 60F-254 or
aluminum oxide 150F-254 neutral (type T) sheets.
Preparative TLC was performed using Merck silica gel
60GF-254 with a plate thickness of 1 mm. Column
chromatography was carried out using silica gel 60 (0.063–
0.20 mm and 0.04–0.063 mm). ‘‘Flash chromatography’’
refers to the method reported by Still.38 Liquid chromatogra-
phy was performed on a Varian 5000 Liquid Chromatography
employing a reverse phase (C-18) column, and preparative
HPLC was done on a Waters PREP-500 with a SiO2 column.
2,3a
observed in dienolate chemistry,
which is therefore
consistent with, but not proof of, reaction via free enolates.
The reaction of Z-4a with aromatic and aliphatic aldehydes
mediated by TiCl4 gives syn-a-condensation products 6a–
6h, and is proposed to proceed by a chair-like transition
state featuring bidentate coordination to titanium (11). Fur-
ther refinement by DFT calculations suggest involvement
of the ‘‘outside TMS’’ 15 over the ‘‘inside TMS’’ 14 tran-
sition state. Although limited in scope, the diastereoselec-
tivity observed for the TiCl4-mediated reactions of a,b-
unsaturated amides is complementary to that observed on
analogous stannyl- and germyl-senecioates.21,22
The utility of the reported chemistry for the construction
of diasteriomerically pure functionalized amides, especially
in view of the recent availability of a mild method for amide
to aldehyde conversion using the Schwartz reagent,37 and
adaption to enantioinduction modes of reaction may create
further opportunities in synthetic chemistry.
All dry solvents were employed after distilling from the ap-
propriate drying agent.39 Diethyl ether (Et2O), benzene, and
tetrahydrofuran (THF) were distilled from benzophenone-
ketyl immediately prior to use. Solutions of n-BuLi were
titrated with 2,5-dimethoxybenzyl alcohol as a standard.40
Diisopropylamine was dried and distillated over CaH2 and
Experimental section
General methods
Elemental analyses were performed by M-H-W Laborato-
ries, Phoenix, Arizona. Melting points were determined on a
Buchi SMP-20 instrument and are uncorrected. Infrared
spectra were determined on a PerkinElmer 983 spectropho-
tometer. 1H NMR spectra were determined with Bruker
WP-80, Bruker AM-250, and Bruker Avance-500 spectrom-
eters. The spectra were recorded at 80 MHz in CDCl3 with
tetramethylsilane as an internal standard unless otherwise
stated. Spectral features are tabulated in the following order:
chemical shift (d, ppm), number of protons; multiplicity
˚
stored in brown bottles over 4 A molecular sieves in a des-
sicator containing CaCl2. All other reagents were purified
according to literature procedures. All lithiation reactions,
and fluoride- or Lewis acid mediated reactions of Z-4a were
carried out under high purity nitrogen or argon (Linde).
Tetra(n-butylammonium) fluoride (TBAF, 1 mol/L in THF)
˚
was allowed to sit over 4 A molecular sieves for approxi-
Published by NRC Research Press

752
Can. J. Chem. Vol. 87, 2009
mately 15 min prior to use. Amides 1a and 1c were prepared
action mixture was subjected to
without prior heating.
a standard workup
by literature procedures.3a
The term ‘‘–78 8C’’ refers to the temperature of a CO2 –
acetone bath (normally –75 to –78 8C). The term ‘‘at –45 8C’’
refers to a reaction done in an acetonitrile–CO2 slush bath
(normally –45 to –50 8C). The term ‘‘at 0 8C’’ refers to a re-
action done in an ice bath.
The phrase ‘‘workup in the usual manner’’ or ‘‘standard
workup’’ refers to addition of saturated aqueous NH4Cl to
the reaction mixture, followed by evaporation of the organic
solvent under reduced pressure, extraction of the residue
with CH2Cl2 or diethyl ether (Et2O), drying of the organic
extract over MgSO4, followed by filtration, and subsequent
evaporation to dryness under reduced pressure to afford the
crude product. Subsequent chromatography and (or) recrys-
tallization and (or) distillation of the crude material afforded
pure products.
N,N-diethylsenecioamide(N,N-diethyl-3-methyl-Z-
butenamide) 1b
To a solution of senecioic acid (5.72 g, 57.1 mmol) in
benzene (60 mL) under a drying tube was added thionyl
chloride (9 mL, 123 mmol). The solution was allowed to
stir overnight. The benzene and excess thionyl chloride
were removed by evaporation under reduced pressure, and
the resulting senecioyl chloride was slowly added to dieth-
ylamine (20 mL, 193 mmol) in diethyl ether (75 mL). The
resulting mixture was subjected to filtration, and the filtrate
was successively washed with H2O (50 mL), 10% aqueous
NaOH (2 ꢁ 50 mL), and H2O (50 mL). The ethereal layer
was dried over MgSO4, subjected to filtration, and the fil-
trate was concentrated in vacuo. Distillation of the crude
product gave 6.19 g (70%) of 1b, bp 37.5–38.5 8C at 0.02
torr (1 torr = 133.322 Pa). IR (neat) nmax: 1653, 1624 cm–1.
1H NMR, d: 1.14 (t, J = 7, 6H), 1.84 (s, 3H), 1.93 (s, 3H),
3.37 (2 q, overlapping, J = 7, 4H), 5.81 (br s, 1H). MS m/e
(rel. intensity): 155 (M+, 25), 140(27), 83(100). Anal. calcd.
for for C9H17NO: C, 69.63; H, 11.04; N. 9.02. Found: C,
69.70; H, 11.21; N, 9.18.
DFT calculations were carried out using the B88-PW91
method, and a DZVP basis set, using CAChe1 version
6.1.12.33 (see Supplementary data). All stationary points
were confirmed via frequency calculations.
General procedure for the formation of lithium
dienolates
Z-N,N,3-trimethyl-1-trimethylsiloxyl-3-butadienamine 2a
N,N-Dimethylsenecioamide 1a (1.916 g, 15.1 mmol) was
lithiated according to procedure C. Chlorotrimethylsilane
(1.91 mL, 15.1 mmol) was then added to the solution at
0 8C. After stirring for 20 min, the solvent was evaporated
under reduced pressure, and hexane (20 mL) was added.
This mixture was subjected to filtration through glass wool,
and the hexane filtrate was evaporated under reduced
pressure. An NMR spectrum of the crude product revealed
Preparation of LDA
Diisopropylamine (5 mmol, 0.70 mL) was dissolved in
THF (25 mL) and cooled to 0 8C. To this solution, n-BuLi
(5 mmol) was added by syringe injection over a period of
~30 s. The solution was then stirred for a further 0.5 h at
0 8C.
Lithiation with LDA
1
Procedure A — The amide in question was added by
syringe to 1.05 equiv. of LDA in THF at –78 8C such that
the concentration in solution was roughly 0.2 mol/L. This
solution was stirred at –78 8C for 1 h prior to electrophile
addition.
the presence of 2a. H NMR (C6D6) d: 0.18 (s, 9H), 2.06 (s,
3H), 2.26 (s, 6H), 4.48 (s, 1H), 4.67, 5.16 (2 m, 2H).
Irradiation of the resonance at 2.26 ppm gave rise to a 7%
integrated enhancement of the 4.48 ppm peak. 13C NMR
(C6D6): 0.4, 24.6, 40.6, 92.0, 109.3, 140.7, 155.1.
Procedure B — The amide in question was added by
syringe to 1.05 equiv. of LDA in THF at 0 8C such that the
concentration in solution was roughly 0.2 mol/L. This
solution was stirred at 0 8C for 0.5 h prior to electrophile
addition.
Z- and E-N,N,3-Methyl-4-trimethylsilyl-2-butenamide Z-4a
and E-4a
N,N-Dimethylsenecioamide 1a (8.2 mL, 60 mmol) was
lithiated according to procedure A and silylated with
chlorotrimethylsilane (8.4 mL, 66 mmol) in the normal
manner for silylation (reflux 18 h) followed by a standard
workup. Preparative HPLC (5:2 hexane – ethyl acetate)
gave, in order of elution: Z-4a (8.9 g, 74%), bp 50–53 8C
Procedure C — The amide in question was added by
syringe to 1.05 equiv. of LDA in THF at RT such that the
concentration of the amide or amide dienolate in solution
was roughly 0.2 mol/L. This solution was stirred at RT for
1 h prior to electrophile addition.
1
at 0.01 torr. IR (neat) nmax: 1646 cm–1. H NMR (C6D6) d:
0.11 (s, 9H), 1.66 (d, J = 1.4, 3H), 2.41 (d, J = 0,6, 2H),
2.54 (br s, 6H), 5.62 (br s, 1H). 13C (125 MHz) d: –1.0,
25.9, 27.4, 34.9, 37.5, 113.3, 152.1, 168.4. MS m/e (rel.
intensity): 199 (M+, 3), 184(100), 157(10), 58(20). Anal.
calcd. for C10H21NOSi: C, 60.30; H, 10.55; N 7.04. Found:
C, 60.22; H, 10.51; N, 7.01. E-4a (0.1915 g, 2%), bp 61–
63 8C at 0.17 torr. IR (neat) nmax: 1610 cm–1. 1H NMR
(C6D6) d: –0.05 (s, 9H), 1.46 (d, J = 0.7, 2H), 2.16 (d,
J = 1.2, 3H), 2.51, 2.70 (2 br s, 6H), 5.60 (br s, 1H). MS
m/e (rel. intensity): 199 (M+, 18), 184(100), 155(25),
73(100). Anal. calcd. for C10H21NOSi: C, 60.30; H, 10.55;
N 7.04. Found: C, 60.27; H, 10.61; N, 7.04. A third frac-
Silylations of lithium dienolates
To the solution of the lithium dienolate in THF at –
78 8C was added, by syringe, 1.1 equiv. of the chlorosi-
lane. The resulting solution was stirred at –78 8C for
0.5 h before the low temperature bath was removed and
the reaction mixture allowed to warm to RT. Unless the
silylating reagent was diphenylmethylsilyl chloride, the re-
action mixture was then heated to reflux for the indicated
amount of time, after which a standard workup was per-
formed. In the case of chloromethyldiphenylsilane, the re-
Published by NRC Research Press

Green et al.
753
tion (0.9631 g, 13%) proved to be a mixture of the starting
5.18. A mixture of the starting material and its deconjugated
double bond isomer 10a (0.140 g, 23%).
material 1a and its deconjugated isomer 10a.3a
Z- and E-N,N,3-Trimethyl-4-triethylsilyl-2-butenamide Z-
4b and E-4b
Z- and E-N,N,3-Trimethyl-3-methyl-4-methyldiphenylsilyl-
2-butenamide Z- and E-4d
N,N-Dimethylsenecioamide, 1a (0.70 mL, 5.0 mmol), was
lithiated according to procedure A, and the resulting dieno-
late was silylated with 0.92 mL (5.5 mmol) of chlorotrie-
thylsilane in the normal manner. After a standard workup,
column chromatography gave, in order of elution: Z-4b
N,N-Dimethylsenecioamide, 1a (0.275 mL, 2.0 mmol),
was lithiated according to procedure A, and the resulting di-
enolate was silylated with diphenylmethylsilyl chloride
(0.46 mL, 2.2 mmol) in the normal manner (no reflux). The
crude reaction mixture was subjected to preparative TLC
(3:1 hexane – ethyl acetate) to give two fractions, in order
of elution: Z-4d (0.214 g, 33%), mp 56–58 8C (petroleum
(0.71 g, 58%), bp 83–84 8C at 0.17 torr. IR (neat) nmax
:
1642 cm–1. H NMR (C6D6) d: 0.5–1.2 (A2B3 spin system,
15H), 1.69 (d, J = 1.2, 3H), 2.46 (s, 2H), 2.56 (br s, 6H),
5.63 (br s, 1H). MS m/e (rel. intensity): 241 (M+, 4),
226(93), 212(100), 198(45), 115(10), 87(27). HR-MS calcd.
for C13H27NOSi: 241.1863. Found: 241.1847. E-4b (0.21 g,
18%), bp 94–96 8C at 0.15 torr. IR (neat) nmax: 1642,
1
1
ether). IR (CCl4) nmax: 1633, 1610 cm–1. H NMR d: 0.58
(s, 3H), 1.64 (s, 3H), 2.83 (2 s, overlapping, 8H), 5.69 (s,
1H), 7.2–7.7 (m, 10H). MS m/e (rel. intensity): 323 (M+,
12), 308(100), 246(18), 232(22), 197(100). Anal. calcd. for
C20H25NOSi: C, 74.25; H, 7.79; N, 4.33. Found: C, 74.48;
H, 7.87; N, 4.38. E-4d (0.380 g, 59%), mp 50.5–51.5 8C
(petroleum ether). IR (neat) nmax: 1639, 1613 cm–1. 1H
NMR d: 0.63 (s, 3H), 1.87 (d, J = 1.0, 3H), 2.20 (s, 2H),
2.64, 2.87 (2s, 6H), 5.55 (br s, 1H). MS m/e (rel. intensity):
323 (M+, 4), 308(45), 232(12), 197(100). Anal. calcd. for
C20H25NOSi: C, 74.25; H, 7.79; N, 4.33. Found: C, 74.07;
H, 7.83; N, 4.33.
1
1618 cm–1. H NMR (C6D6) d: 0.4–1.0 (A2B3 spin system,
15H), 1.54 (d, J = 1.0, 2H), 2.19 (d, J = 1.5, 3H), 2.51,
2.73 (2 br s, 6H), 5.68 (br s, 1H). MS m/e (rel. intensity):
241 (M+, 8), 226(100), 212(76), 198(93). Anal. calcd. for
C13H27NOSi: C, 64.67; H, 11.27; N 5.80. Found: C, 64.49;
H, 11.11; N, 6.01.
N,N-Dimethylsenecioamide, 1a (0.67 mL, 4.9 mmol) was
lithiated according to procedure A. To the resulting dieno-
late, at –78 8C, was added chlorotriethylsilane (0.92 mL,
5.5 mmol). After stirring the solution for 0.5 h at –78 8C,
the solution was allowed to warm to RT, and the solvents
were removed under reduced pressure. A small amount of
Z- and E-N,N-Diethyl-3-methyl-4-trimethylsilyl-2-
butenamide Z- and E-4e
N,N-Diethylsenecioamide, 1b (0.780 g, 5.02 mmol), was
lithiated according to procedure A, and the resulting dieno-
late was silylated with chlorotrimethylsilane (0.7 mL,
5.5 mmol) in the normal manner (reflux 17 h). The crude
reaction mixture was subjected to preparative HPLC (3:1
hexane – ethyl acetate) to give, in order of elution: Z-4e
1
the residual material was removed; the H NMR spectrum
(C6D6) of this sample showed d 4.35 (s, vinyl CH of 2b)
and d 5.62 (br s, vinyl CH of Z- and E-4b) with rel.ative in-
tegrals of 77:23. The rest of the material was worked up in
the usual manner, and the resultant crude product subjected
to preparative HPLC. Three fractions were isolated. The first
fraction (0.048 g, 4%) contained Z-4b (see above for spec-
tral data). The second fraction (0.20 g, 16%) was shown to
be E-4b (see above for spectral data). The third fraction
(0.34 g, 53%) was found to contain a mixture of the starting
1a and its b,g-unsaturated isomer 10a.
(0.446 g, 39%), bp 90–95 8C at 0.6 torr. IR (neat) nmax
:
1637, 1612 cm–1. H NMR (C6D6) d: 0.15 (s, 9H), 0.90 (br,
12H), 1.68 (d, J = 1.5, H), 5.51 (s, 2H), 3.10 (br, 2H), 5.70
(br s, 1H). MS m/e (rel. intensity): 227(2), 212(100), 73(30).
Anal. calcd. for C12H25NOSi: C, 63.38; H, 11.08; N, 6.16.
Found: C, 63.19; H, 10.92; N, 6.20. E-4e (0.395 g, 35%), bp
1
1
65–70 8C at 0.005 torr. IR (neat) nmax: 1641, 1617 cm–1. H
NMR (C6D6) d: –0.05 (s, 9H), 0.93 (br, 12H), 1.47 (d, J =
1.0, 2H), 2.18 (d, J = 1.5, 3H), 3.16 (br, 2H), 5.66 (br s,
1H). MS m/e (rel. intensity): 227 (M+, 8), 212(100),
155(26), 73(113). Anal. calcd. for C12H25NOSi: C, 63.38; H,
11.08; N, 6.16. Found: C, 63.64; H, 11.43; N, 6.57. A mix-
ture of the starting material Z-4e and its deconjugated double
bond isomer 10b (0.0912 g, 12%).
Z- and E-N,N,3-Trimethyl-4-triisopropylsilyl-2-butenamide
Z- and E-4c
N,N-Dimethylsenecioamide, 1a (0.66 mL, 4.8 mmol), was
lithiated according to procedure A, and the resulting dieno-
late was silylated with 1.2 mL of chlorotriisopropylsilane
(5.5 mmol) in the normal manner (reflux 40 h). Following
standard workup, the crude mixture was subjected to prepa-
rative HPLC (ethyl acetate – hexane) to give, in order of
elution: Z-4c (0.31 g, 23% bp 80–85 8C at 0.005 torr. IR
Z- and E-N,N-Diethyl-3-nethyl-4-triethylsilyl-2-butenamide
Z- and E-4f
1
(neat) nmax: 1641 cm–1. H NMR (C6D6, 250 MHz) d: 1.1–
N,N-Diethylsenecioamide, 1b (0.6606 g, 5.03 mmol) was
lithiated according to procedure A, and the resulting dieno-
late was silylated with chlorotriethylsilane (0.88 mL,
5.5 mmol) in the usual manner (reflux, 18 h). After a stand-
ard workup, flash chromatography (fine silica, 8:l hexane –
ethyl acetate) yielded, in order of elution, two significant
fractions: Z-4f (0.2805 g, 21%), bp 95–100 8C at 0.01 torr.
1.3 (AB, spin system, 21H), 1.76 (d, J = 1.2, 3H), 2.40,
2.71 (2 br s, 6H), 2.59 (s, 2H), 5.64 (s, 1H). MS m/e (rel.
intensity): 283 (M+, 1), 268(6), 240(100), 226(18). HR-MS
calcd. for C16H33NOSi: 283.2333. Found: 283.2314. E-4c
(0.18 g, 14%), bp 70–4 8C at 0.005 torr. IR (neat) nmax
:
1641 cm–1. H NMR (C6D6) d: 1.05–1.2 (AB6 spin system,
21H), 1.76 (d, J = 1.0, 3H), 2.51 (br s, 6H), 2.57 (s, 2H),
5.64 (br s, 1H). MS m/e (rel. intensity): 283 (M+, 3),
268(7), 240(100), 226(22). Anal. calcd. for C16H33NOSi: C,
67.78; H, 11.73; N, 4.94. Found: C, 67.58; H, 11.96; N;
1
1
IR (neat) nmax: 1637, 1614 cm–1. H NMR (C6D6) d: 0.5–1.2
(m, 21H), 1.71 (d, J = 1.2, 3H), 2.54 (s, 2H), 3.05 (br, 4H),
5.69 (br s, 1H). MS m/e (rel. intensity): 269 (M+, 3),
254(100), 240(88), 226(22), HR-MS calcd. for C15H31NOSi:
Published by NRC Research Press

754
Can. J. Chem. Vol. 87, 2009
269.2176. Found: 269.2152. E-4f (0.6270 g, 47%), bp 79–
83 8C at 0.01 torr. IR (neat) nmax: 1641, 1616 cm–1. 1H
NMR (C6D6) d: 0.3–1.1 (m, 21H), 1.55 (s, 2H), 2.22 (d, J =
1.2, 3H), 3.15 (br, 4H), 5.73 (br s, 1H). MS m/e (rel. inten-
sity): 269 (M+, 6), 254(100), 240(31), 226(23). Anal. calcd.
for C15H31NOSi: C, 66.85; H, 11.59; N, 5.28. Found: C,
67.04; H, 11.35; N, 5.28.
syringe. The resulting brown solution was stirred at ambient
temperature for 16 h and worked up in the usual manner.
Kinetic conditions
To a 0.3–0.4 mol/L solution of Z-4a in THF under an in-
ert atmosphere was added 1.2 equiv. of the aldehyde or ke-
tone in question. The solution was cooled to –45 8C before a
1 mol/L solution of TBAF (in THF) was added by syringe.
The resulting solution was stirred at –45 8C for 2 min before
saturated aqueous NH4Cl was added (at –45 8C), and a
standard workup was performed.
Z- and E-N,N-Diisopropyl-3-methyl-4-trimethylsilyl-2-
butenamide Z- and E-4g
N,N-Diisopropylsenecioamide 1c (1.03 mL, 5 mmol) was
lithiated according to procedure A. To the resulting solution
of the dienolate was added, at –78 8C, 0.70 mL (5.5 mmol)
of chlorotrimethylsilane. The mixture was allowed to stir
at –78 8C for 15 min before warming to RT, and subsequent
heating to 40 8C for 36 h. After a standard workup, the
crude product was subjected to preparative HPLC (5:1 hex-
ane – ethyl acetate), resulting, in order of elution, in two
fractions: Z-4g (0.290 g, 23%), bp 57–60 8C at 0.02 torr. IR
TiCl4-mediated aldol condensations of Z-4a
To 1.2 equiv. of the aldehyde in question under an inert
atmosphere was added CH2Cl2 such that the eventual con-
centration of Z-4a was 0.3 mol/L. This solution was cooled
to 0 8C, 1.1 equiv. of TiCl4 was added by syringe, and the
mixture was allowed to stir for 5 min. At this point, a solu-
tion of Z-4a, in a minimum amount of CH2Cl2, was added
by syringe. The ice-bath was immediately removed, and the
reaction mixture was allowed to stir for 3 h during which
time it reached ambient temperature. A standard workup
was then performed.
1
(neat) nmax: 1649, 1632 cm–1. H NMR (C6D6) d: 0.13 (s,
9H), 1.15 (br, 12H), 1.67 (d, J = 1.4, 3H), 2.33 (s, 2H),
3.54 (br, 2H), 5.64 (br s, 1H). MS m/e (rel. intensity): 255
(M+, 4), 240(100), 212(66), 198(22), 171(25), 155(32),
73(145). Anal. calcd. for C14H29NOSi: C, 65.82; H, 11.44;
N, 5.48. Found: C, 66.00; H, 11.46; N, 5.58. E-4g, bp 64–
66 8C at 0.02 torr. IR (neat) nmax: 1626 cm–1. 1H NMR
(C6D6) d: –0.04 (s, 9H), 1.21 (br, 12H), 1.45 (s, 2H), 2.00
(d, J = 1.2, 2H), 3.62 (br, 2H), 5.59 (br s, 1H). MS m/e (rel.
intensity): 255 (M+, 11), 240(36), 212(38), 155(100),
73(144). Anal. calcd. for C14H29NOSi: C, 65.82; H, 11.44;
N, 5.48. Found: C, 65.66; H, 11:22; N, 5.49.
syn- and anti-Z-Hydroxyphenylmethyl-N,N,3-trimethyl-3-
butenamide syn- and anti-6a
TiCl4-mediated reaction
A mixture of compound Z-4a (0.3247 g, 1.63 mmol) and
benzaldehyde (0.20 mL) in the presence of TiC14 (0.20 mL)
was allowed to react in the manner described earlier. After a
standard workup, column chromatography (1:l hexane –
ethyl acetate) gave one fraction, 0.2763 g, which proved to
be a 90:10 mixture (by 1H NMR integration) of syn-6a
(67%) and starting material Z-4a (7%). Recrystallization
gave pure syn-6a, mp 59.5–61 8C (Et2O – petroleum ether)
Z- and E-N,N-Diisopropyl-3-methyl-4-methyldiphenylsilyl-
2-butenamide Z- and E-4h
N,N-Diisopropylsenecioamide (0.9223 g, 5.03 mmol) was
lithiated according to procedure A, and the resulting dieno-
late was treated with chloromethyldiphenylsilane (1.16 mL,
5.5 mmol) in the normal manner (no subsequent heating).
After a standard workup, the crude product was subjected to
column chromatography (4:1 hexane – ethyl acetate), yield-
ing, in order of elution, two fractions: Z-4h (1.025 g, 54%),
1
(Lit.3a 59–61 8C (Et2O – hexane)) whose H NMR spectral
data were identical to those reported.3a
TBAF-mediated reaction
A mixture of compound Z-4a (0.3217 g, 1.61 mmol) and
benzaldehyde (0.20 mL) in the presence of TBAF (1.61 mL
of a 1 mol/L solution) was allowed to react under the previ-
ously described kinetic control conditions. After a standard
workup, the crude reaction mixture was subjected to prepa-
rative TLC (5:2 ethyl acetate – hexane) to give, in order of
elution: syn-6a (0.1145 g, 30%), and 72:16:12 mixture (by
1H NMR integration) (0.1610 g) of anti-6a (33%), Z-4a
(6%), and desilylated material (7%). anti-6a was purified
by recrystallization, mp 113–114 8C (CH2Cl2 – hexane)
1
mp 56–58 8C (hexane). IR (neat) nmax: 1636, 1615 cm–1. H
NMR d: 0.58 (s, 3H), 1.26 (br, 12H), 1.56 (d, J = 1.5, 3H),
2.80 (s, 2H), 3.78 (br, 2H), 5.68 (br s, 1H), 7.2–7.7 (m,
10H). MS m/e (rel. intensity): 379 (M+, 7), 364(61),
336(35), 295(23), 197(100). Anal. calcd. for C24H33NOSi:
C, 75.60; H, 8.76; N, 3.69. Found: C, 75.72; H, 8.67; N,
3.64. E-4h (0.7200 g, 38%), bp 170–175 8C at 0.005 torr.
1
IR (neat) nmax: 1644, 1620 cm–1. H NMR d: 0.63 (s, 3H),
1.12 (br, 12H), 1.77 (d, J = 1.2, 3H), 2.17 (s, 2H), 3.47 (br,
2H), 5.46 (br s, 1H), 7.2–7.7 (m, 10H, 2C6H5). MS m/e (rel.
intensity): 379 (M+, 7), 364(58), 336(34), 295(22), 197(100).
Anal. calcd. for C24H33NOSi: C, 75.93; H, 8.76; N, 3;69;
Found: C, 75.60; H, 8.53; N, 3.96.
1
(Lit.3a 114–114.5 8C (Et2O)) and showed H NMR spectral
data consistent with those reported.3a
Z- and E-5-Hydroxy-N,N,3-trimethyl-5-phenyl-2-
pentenamide Z- and E-5a
A mixture of compound Z-4a (0.3770 g, 1.89 mmol) and
benzaldehyde (0.23 mL) in the presence of TBAF (0.1 mL
of a 1 mol/L solution) was allowed to react under the previ-
ously described thermodynamic control conditions. Follow-
ing a workup in the usual manner, separation by flash
chromatography (fine silica, 4:l ethyl acetate – hexane)
gave, in order of elution: Z-5a (0.2564 g, 58%), mp 75–
TBAF-mediated aldol condensations of Z-4a
Thermodynamic conditions
To a 0.3–0.4 mol/L solution of Z-4a in THF under an
inert atmosphere was added 1.2 equiv. of the aldehyde or
ketone in question. Five mol% of a 1 mol/L solution of tet-
ra(n-butylammonium) fluoride (in THF) was then added by
Published by NRC Research Press

Green et al.
755
77 8C (CH2Cl2 – hexane) (Lit.3a 76–76.5 8C (CH2Cl2 – hex-
ane)), and E-5a (0.0625 g, 14%) as an undistillable viscous
3.5, 1H), 3.01, 3.05 (2s, 6H), 3.0 (obscured, 1H), 4.89 (dd,
J = 10 and 3, 1H), 6.16 (br s, 1H), 6.2 (br, 1H, exchange-
able), 7.27 (m, 1H), 7.87 (m, 1H), 8.4–8.7 (m, 2H). MS m/e
(rel. intensity): 235 (M+ + l, 4), 189(44), 162(29), 144(86),
112(100). HR-MS calcd. for C13H18N2O2 + H: 235.1448.
Found: 235.1452. Fraction 2 was shown to be E-5c
(0.0536 g, 13%) as an undistillable, viscous oil. IR (neat)
1
oil. IR (neat) nmax: 1647, 1606 cm–1. H NMR d: 1.89 (d, J =
1.2, 3H), 2.49 (d, J = 7, 2H), 2.81, 2.90 (2s, 6H), 3.51 (br,
1H, exchangeable), 4.85 (t, J = 7, 1H), 5.76 (br s, 1H), 7.32
(s, 5H). MS m/e (rel. intensity): 234 (M+ + l, 3), 215(11),
127(100), 112(25). HR-MS calcd. for C14H19NO2 + H:
234.1495. Found: 234.1492.
1
nmax: 3344, 1646, 1607 cm–1. H NMR d: 1.92 (s, 3H), 2.49
(d, J = 7, 2H), 2.87, 2.91 (2s, 6H), 4.6 (br, 1H, exchange-
able), 4.92 (t, J = 7, 1H), 5.81 (br s, lH), 7.28 (m, 1H), 7.73
(m, 1H), 8.52 (m, 2H). MS m/e (rel. intensity): 234 (M+, 2),
216(40), 171(44), 144(63), 127(100), 109(63). HR-MS
calcd. for C13H18N2O2: 234.1369. Found: 234.1362.
syn- and anti-2-(3,4-Dimethoxy)phenylhydroxyethyl-N,N,3-
trimethyl-3-butenamide syn- and anti-6b
A mixture of compound Z-4a (0.2752 g, 1.38 mmol) and ve-
ratraldehyde (0.3238 g) in the presence of TBAF (1.38 mL of a
1 mol/L solution) was allowed to react under the previously
described kinetic control conditions. After a standard workup,
the crude reaction mixture was subjected to preparative TLC
(5:2 ethyl acetate – hexane) yielding two fractions. The first
fraction (0.123 g) was identified by 1H NMR spectroscopy as
a 79:21 mixture of syn-6b (25%) and desilylated starting ma-
terial (7%) from which syn-6b was obtained by recrystalliza-
tion, mp 102–103 8C (Et2O – hexane) (Lit.3a 100–1.5 8C
(Et2O – hexane)). The second fraction (0.1197 g) was shown
syn- and anti-2-Hydroxy(4-pyridyl)methyl-N,N,3-trimethyl-
3-butenamide syn- and anti-6d and Z-5-Hydroxy-5-(4-
pyridyl)-N,N,3-trimethyl-2-pentenamide Z-5d
TBAF-mediated reaction
A mixture of compound Z-4a (0.2720 g, 1.36 mmol) and
4-pyridinecarboxaldehyde (1.9 mL) in the presence of TBAF
(1.37 mL of a 1 mol/L solution) was allowed to react under
kinetic control conditions. After a standard workup, the re-
sulting crude product was subjected to preparative TLC (in
1: 1 ethyl acetate – acetone) to give, in order of elution,
1
to be 81:19 mixture (by H NMR spectroscopy) of anti-6b
(27%) and Z-5b (6%) from which anti-6b was obtained by re-
crystallization, mp 120–12l 8C (Et2O) (Lit.3a 118 8C (CH2C12
1
three fractions identified by H NMR spectroscopy: Fraction
1
– hexane)). Products syn-6b and anti-6b showed H NMR
1 (0.0364 g, 13%) was shown to be starting Z-4a. Fraction 2
was identified as a 1:l mixture of syn- and anti-6d
(0.1718 g), while fraction 3 was shown to be a 35:65 mix-
ture of anti-6d and Z- 5d (0.0646 g). The individual isomers
of 6d were purified by recrystallization: syn-6d (27%), mp
111–113 8C (CH2Cl2 – Et2O – hexane) (Lit.3a 98–99 8C
(CH2Cl2 – hexane)), mixture mp 109–116 8C. anti-6d
(34%), mp 125 8C (CH2Cl2 – hexane) (Lit.3a 128–129 8C
(CH2Cl2 – hexane)). Compounds syn-6d and anti-6d showed
1H NMR spectral data consistent with those reported.3a
spectral data consistent with those reported.3a
Z- and E-5-(3,4-Dimethoxy)phenyl-5-hydroxy-N,N,3-
trimethyl-2-pentenamide Z- and E-5b
A mixture of compound Z-4a (0.4695 g, 2.36 mmol) and
veratraldehyde (0.4695 g) in the presence of a catalytic
amount of TBAF (0.12 mL of a 1 mol/L solution) was al-
lowed to react under the previously described thermodynamic
control conditions, followed by workup under the usual con-
ditions. The crude mixture was subjected to column chroma-
tography, yielding three fractions. Fraction 1 (0.067 g, 12%)
was shown to be desilylated starting material 1a/10a. Fraction
2 (0.3520 g, 49%) was shown to be Z-5b, mp 78–80 8C
(CH2C12 – hexane) (Lit.3a 78–80 8C (CH2Cl2 – hexane)) by
1
Compound Z-5d (13%) was identified by its H NMR spec-
trum (see below).
A mixture of compound Z-4a (0.3804 g, 1.908 mmol) and
4-pyridinecarboxaldehyde in the presence of TBAF
(0.10 mL of a 1 mol/L solution) was allowed to react under
thermodynamic control conditions. After a standard workup,
chromatography on aluminum oxide (activity III, 5:2 ethyl
acetate – hexane) gave two fractions. Fraction 1 (0.2813 g)
was identified as a 2:l mixture of Z-5d (42%) and syn-6d
(21%). Fraction 2 proved to be anti-6d (0.0743 g, 17%).
Compound Z- 5d was further purified by repeated prepara-
tive TLC, but remained a viscous, undistillable oil. IR
1
comparison with its H NMR spectra with that reported.3a
Fraction 3 (0.1880 g, 26%) proved to be E-5b as an undistil-
1
lable viscous oil. IR (neat) nmax: 3378, 1646, 1608 cm–1. H
NMR d: 1.93 (d, J = 1.2, 3H), 2.50 (d, J = 7, 2H), 2.90, 2.94
(2s, 6H), 3.87, 3.89 (2s, 6H), 4.83 (t, J = 7, 1H), 5.82 (br s,
1H), 6.8–7.0 (m, 3H), OH not observed. MS m/e (rel. inten-
sity): 293 (M+, 3), 127(100), 112(27). HR-MS calcd. for
C16H23NO4: 293.1628. Found: 293.1629.
1
(neat) nmax: 3229, 1637, 1598 cm–1. H NMR d: 1.95 (s,
3H), 2.33 (d, J = 13 and 3, 1H), 3.00, 3.05 (2s, 6H), 3.0 (ob-
scured, 1H), 4.85 (br d, J = 10, 1H), 6.17 (br s, 1H), 7.35,
8.55 (AA’BB’ spin system, J = 6, 4H), OH not observed.
MS m/e (rel. intensity): 235 (M+ + l, 2), 216(33), 127(100),
112(68), 83(30). HR-MS calcd. for C13H18N2O2 + H:
235.1448. Found: 235.1454.
Z- and E-5-Hydroxy-5-(3-pyridyl)-N,N,3-trimethyl-2-
pentenamide Z- and E-5c
A mixture of compound Z-4a (0.3428 g, 1.72 mmol) and
3-pyridinecarboxaldehyde (0.18 mL) in the presence of a
catalytic amount of TBAF (0.17 mL of a 1 mol/L solution)
was allowed to react under the previously described thermo-
dynamic control conditions. Following a standard workup,
the crude product was subjected to column chromatography
(100% acetone) yielding two fractions. Fraction 1 was
shown to contain Z-5c (0.2289 g, 57%) as an undistillable,
viscous oil. IR (neat) nmax: 3223, 1648, 1598 cm–1. 1H
NMR d: 1.96 (d, J = 1.4, 3H, CH3), 2.32 (dd, J = 13 and
syn- and anti-2-Hydroxy(4-nitro)phenylmethyl-N,N,3-
trimethyl-3-butenamide syn- and anti-6e and Z-5-Hydroxy-
5-(4-nitro)phenyl-N,N,3-trimethyl-2-pentenamide Z-5e
TiCl4-mediated reaction
A mixture of compound Z-4a (0.3766 g, 1.89 mmol) and
Published by NRC Research Press

756
Can. J. Chem. Vol. 87, 2009
4-nitrobenzaldehyde (0.3429 g) in the presence of TiC14
(0.23 mL) was allowed to react under the previously de-
scribed conditions. After a standard workup, the crude reac-
tion product was subjected to column chromatography (3:2
ethyl acetate – hexane) to give in order of elution: syn-6e
(0.3578 9, 73%), mp 119.5–121 8C (Et2O – hexane). IR
tography (fine silica, 3:1 – 9:l ethyl acetate – hexane), to
give, in order of elution: Z-5f (0.1872 g, 20%). IR (neat)
1
nmax: 1623 cm–1. H NMR (C6D6) d: –0.13 (s, 9H), 1.92 (s,
3H), 2.34, 2.78 (2s, 6H), 3.76 (s, 2H), 5.57 (br s, 1H), 7.36
(apparent s, 10H). This compound slowly underwent
desilylation on standing to give Z-5g, mp 143–145 8C
(Et2O – petroleum ether). IR (CHCl3) nmax: 3191, 1643,
1
(CHCl3) nmax: 3404, 1624 cm–1. H NMR d: 1.64 (s, 3H),
1
1598. cm–1. H NMR d: 1.25 (s, 3H), 2.96, 3.03 (2 s, 6H),
2.96 (s, 6H), 3.42 (d, J = 3.7, 1H), 4.51, 4.96 (2s, 2H), 5.26
(s, 1H, exchangeable), 5.36 (d, J = 3.7, 1H), 7.54 and 8.18
(AA’BB’ spin system, J = 9, 4H). MS m/e (rel. intensity):
278 (M+, 1), 127(100), 112(90), 83(100). Anal. calcd. for
C14H18N2O4: C, 60.42; H, 6.52; N, 10.07. Found: C, 60.66;
H, 6.51; N, 10.21. anti-6e (0.0047 g, 1%), mp 177–178 8C
3.42 (s, 2H), 6.08 (br s, 1H), 7.1–7.7 (m, 10H), 7.41 (s, 1H,
exchangeable). MS m/e (rel. intensity): 291 (M+ –18, 8),
182(49), 128(41), 105(100), 84(24), 77(48), 72(32). Anal.
calcd. for C20 H23NO2: C, 77.64; H, 7.49; N, 4.53. Found:
C, 77.16; H, 7.46; N, 4.62. E-5f (0.4418 g, 48%), mp 65–
67 8C (Et2O – petroleum ether). IR (CHCl3) nmax: 1646,
1
(CH2Cl2 – hexane). IR (CHCl3) nmax: 3443, 1626 cm–1. H
1
1610 cm–1. H NMR (C6D6) d: –0.12 (s, 9H), 1.71 (s, 3H),
NMR d, 1.69 (s, 3H),. 2.91, 2.94 (2s, 6H), 3.41 (d, J = 6,
1H), 4.65–5.25 (m, 4H; on addition of D2O gives 4.73 (s,
1H), 4.96 (s, 1H), 5.11 (d, J = 6, 1H)), 7.53, 8.19 (AA’BB’
spin system, J = 8, 4H). MS m/e (rel. intensity): 278 (M+, 1),
127(100), 112(38), 83(89). Anal. calcd.. for C14H18N2O4: C,
60.42; H, 6.52; N, 10.07. Found: C, 60.54; H, 6.45; N, 10.06.
2.36, 2.81 (2s, 6H), 3.18 (s, 2H), 5.45 (br s, 1H), 7.25 (s,
10H). MS m/e (rel. intensity): 366 (M+ – 15, 2), 291(6),
255(100), 199(28), 73(100). Anal. calcd. for C22H31NO2Si:
C, 72.39; H, 8.19; N, 3.67. Found: C, 72.62; H, 8.25; N,
3.80.
TBAF-mediated reaction
TiCl4-mediated reaction
A mixture of compound Z-4a (0.3061 g, 1.54 mmol) and
4-nitrobenzaldehyde (0.3139 g) in the presence of TBAF
(1.55 mL of a 1 mol/L solution) was allowed to reaction
under the previously described kinetic control conditions.
Following a standard workup, preparative (5:2 ethyl acetate
– hexane) TLC of the crude product gave, in order of elution:
recovered Z-4a (0.0096 g, 3%), syn-6e (0.1082 g, 25%), and
a 51:49 mixture (by 1H NMR spectroscopy) of anti-6e (31%)
and Z-5e (30%) (0.2631 g). Compound Z-5e was obtained by
crystallization, mp 113–115 8C (CH2Cl2 – Et2O – hexane). IR
A mixture of compound Z-4a (0.211 g, 1.06 mmol) and
benzophenone (0.273 g) in the presence of TiC14 (0.23 mL)
was allowed to react under the previously described condi-
tions. After a standard workup, the crude reaction product
was subjected to column chromatography (3:1 ethyl acetate
– hexane) to afford 6g (0.236 g, 72%), whose spectroscopic
data was shown to be identical with those reported.3a
Z- and E-N,N,3-Trimethyl-5,5-diphenyl-2,4-butadienamide
Z- and E-7
1
(CHCl3) nmax: 3194, 1650, 1598 cm–1. H NMR d: 1.95 (s,
A mixture of compound Z-4a (0.5210 g, 2.61 mmol) and
benzophenone (1.6385 g, 3 equiv.) in the presence of
TBAF (0.13 mL of a 1 mol/L solution) was allowed to re-
act under thermodynamic conditions. After a standard
workup, the crude product was subjected to flash chroma-
tography (4:1 – 9:1 ethyl acetate – hexane) to give a mix-
ture of Z- and E-7 (0.2815 g, 29%), bp 145–150 8C at 0.01
3H), 2.33 (dd, J = 13 and 3), 3.0 (obscured, 1H), 3.01, 3.06
(2 s, 6H), 4.94 (m, 1H; on addition of D2O becomes dd, J =
10 and 3), 6.18 (br s, 1H), 7.19 (d, J = 6, 1H, exchangeable),
7.63, 8.20 (AA’BB’ spin system, J = 9, 4H). MS m/e (rel. in-
tensity): 278 (M+, 2), 260(37), 216(39), 127(100), 112(97),
83(100). Anal. calcd. for C14H18N2O4: C, 60.42; H, 6.52; N,
10.07. Found: C, 60.35; H, 6.44; N, 9.93.
1
torr. IR (neat) nmax: 1630 cm–1. H NMR d: 1.56 and 1.81
A mixture of compound Z-4a (0.3053 g, 1.53 mmol) and
4-nitrobenzaldehyde (0.2905 g) in the presence of TBAF
(0.08 mL of a 1 mol/L solution) was allowed to reaction
under the previously described thermodynamic control
conditions. After a standard workup, the crude product was
subjected to column chromatography (2:1 – 4:1 ethyl ace-
tate – hexane) to give, in order of elution, two fractions:
syn-6e (0.0926 g, 22%) and a 46:54 mixture of anti-6e
(27%) and Z-5e (31%) (0.2468 g).
(s, 3H), 2.65 and 2.89 (s, 6H), 5.89 (br s, 1H), 6.55 and
7.24 (obscured) (br s, 1H), 7.24 (s, 10H). The relative inte-
grals of the 1.8 and 1.56 peaks established the ratio of E-
7:Z-7 as 65:35. MS m/e (rel. intensity): 291 (M+, 38),
219(100), 214(25), 204(49). HR-MS calcd. for C20H21NO:
291.1624. Found: 291.1631.
syn- and anti-2-(1-Hydroxy-l-propyl)-N,N,3-trimethyl-3-
butenamide syn- and anti-6h
A mixture of compound Z-4a (0.4114 g, 2.06 mmol) and
butanal (0.22 mL) in the presence of TiCl4 (0.25 mL) was
allowed to react under the previously described conditions.
Following standard workup, the crude reaction product was
subjected to column chromatography (2:l hexane – ethyl
acetate) to give, in order of elution: syn-6h (0.2552 g,
62%), mp 44–45 8C (Et2O – hexane) (Lit.3a 44–46 8C (Et2O
– hexane)). anti-6h (0.0097 g, 2%), mp 68–70 8C (CH2Cl2 –
hexane) (Lit.3a 70 8C (CH2Cl2 – hexane)) both of which
were shown to exhibit 1H NMR spectral data consistent
with their structures,3a and a mixture of desilylated 2- and
3-butenamides (0.0391 g, 14%).
Z-5-Hydroxy-N,N,3-trimethyl-5,5-diphenyl-2-pentenamide
Z-5g and Z- and E-N,N,3-trimethyl-5,5-diphenyl-5-
trimethylsiloxy-2-pentenamide Z- and E-5f
TBAF-mediated reaction
To a solution of Z-4a (0.4794 g, 2.40 mmol) and
benzophenone (0.5461 g, 1.24 equiv.) in 5 mL of THF
cooled to –45 8C was added TBAF (0.12 mL of a 1 mol/L
solution in THF, 5 mol%). After stirring for 1 h at –45 8C,
the reaction mixture was quenched with saturated aqueous
NH4Cl (at –45 8C) and was worked up in the usual manner.
The resultant crude product was subjected to flash chroma-
Published by NRC Research Press

Green et al.
757
syn- and anti-2-(1-Hydroxy-2-propyl)-N,N,3-trimethyl-3-
butenamide syn- and anti-6i
states 16 and 17, have been deposited as Supplementary
data for this article available on the journal Web site
(canjchem.nrc.ca) or may be purchased from the Depository
of Unpublished Data, Document Delivery, CISTI, National
Research Council Canada, Ottawa, ON K1A 0R6, Canada.
DUD 3932. For more information on obtaining material, re-
fer to cisti-icist.nrc-cnrc.gc.ca/cms/unpub_e.shtml.
A mixture of compound Z-4a (0.3818 g, 1.92 mmol) and
2-methylpropanal (0.21 mL) in the presence of TiC14
(0.23 mL) was allowed to react under the previously de-
scribed conditions. After workup in the usual manner, the
crude reaction product was subjected to column chromatog-
raphy (1:1 – 2:1 ethyl acetate – hexane) to give, in order of
elution, two fractions: syn-6i (0.1520 g, 40%), mp 74–
Acknowledgements
1
74.5 8C (hexane). IR (neat) nmax: 3373, 1619 cm–1. H NMR
We are grateful to the Natural Sciences and Engineering
Research Council of Canada (NSERC) for support of our
synthetic programs. We also wish to thank Prof. James
Gauld, Dr. Haining Liu, and Prof. Charles MacDonald (Uni-
versity of Windsor) for assistance with the DFT calculations
on the allylsilane – aldehyde transition states.
d: 0.96 (m, 6), 1.83 (obscured, 1), 1.83 (s, 3H), 2.95, 3.03
(2s, 6H), 3.41 (d, J = 4.4, 1H), 3.63 (m, 1H), 4.01 (br s, 1H,
exchangeable), 4.01, 4.08 (2 s, 2H). MS m/e (rel. intensity):
199, (M+, 2), 156(31), 127(11)0), 112(95), 83(100), 72(100) .
Anal. calcd. for C11H21NO,: C, 66.30; H, 10.62; N, 7.03.
Found: C, 66.34; H, 10.62; N, 7.05. anti-6i (0.1062 g, 28%),
mp 111.5–112.5 8C (hexane). IR (CHCl3) nmax: 3400,
References
1
1624 cm–1. H NMR d: 0.96 (d, J = 7, 6H), 1.77 (obscured,
(1) Dedicated to Peter Beak, in recognition of a career of rigor-
ous physical organic studies, which enduringly enriched the
field of carbanionic chemistry.
1H), 1.77 (s, 3H), 2.96, 3.00 (2s, 6H), 3.34 (d, J = 5.9, 1H),
3.72 (m, 1H), 3.94 (0.5 of ABq, J = 7, 1H, exchangeable),
4.86, 4.99 (2s, 2H). MS m/e (rel. intensity): 199 (M+, 4),
156(37), 127(100), 112(41), 83(98), 72(82). Anal. calcd. for
C11H21NO2: C, 66.30; H, 10.62; N, 7.03. Found: C, 66.46; H,
10.61; N, 7.08.
(2) (a) Casiraghi, G.; Zanardi, F.; Appendino, G.; Rassu, G.
Chem. Rev. 2000, 100, 1929 doi:10.1021/cr990247i. PMID:
11749280.; (b) Denmark, S. E.; Heemstra, J. R., Jr.; Beutner,
G. L. Angew. Chem., Int. Ed. 2005, 44, 4682 doi:10.1002/
anie.200462338.; (c) Green, J. R. In Science of synthesis;
Majewski, M. and Snieckus, V., Eds; Georg Thieme Verlag:
Stuttgart, 2006; Vol. 8, pp. 427–486; (d) Casinos, I.; Mes-
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J. Org. Chem. 1980, 45, 1181. doi:10.1021/jo01295a002.
(3) (a) Majewski, M.; Mpango, G. B.; Thomas, M. T.; Wu, A.;
Snieckus, V. J. Org. Chem. 1981, 46, 2029 doi:10.1021/
jo00323a012.; (b) Majewski, M.; Green, J. R.; Snieckus, V.
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syn- and anti-2-(1-Hydroxy-2-ethyl)-N,N,3-trimethyl-3-
butenamide syn- and anti-6j
A mixture of compound Z-4a (0.1075 g, 0.539 mmol) and
propanal (58 mL) in the presence of TiC14 (65 mL) was al-
lowed to react under the previously described conditions.
After workup in the usual manner, the crude reaction prod-
uct was subjected to preparative TLC (3:2 ethyl acetate–
hexane) to yield, in order of elution, two fractions: syn-6j
(0.0450 g, 45% yield), bp 72–77 8C at 0.1 torr. IR (neat)
1
nmax 3440, 1634 cm–1. H NMR (500 MHz) d: 0.96 (t, J =
7.2, 3H), 1.40–1.55 (m, 2H), 1.81 (s, 3H), 2.94, 3.00 (2s,
6H), 3.20 (d, J = 4.0, 1H), 3.93 (m, 1H), 4.28 (br s, 1H, ex-
changeable), 4.83 (s, 1H), 5.08 (t, J = 1.5, 1H), 13C NMR:
10.5, 21.9, 27.0, 35.6, 37.3, 54.0, 73.0, 116.8, 139.7, 173.5.
MS m/e (rel. intensity): 185 (M+, 14), 126 (100), 111 (29),
83 (31). HR-MS calcd. for C10H19NO2: 185.1405 (M+),
167.1312 (M+ – H2O). Found: 185.1416, 167.1310. A 53:47
mixture of anti-6j (7%) and desilylated butenamides (6%)
(0.0111g); pure anti-6j was obtained by recrystallization,
(4) Casey, C. P.; Jones, C. R.; Tukada, H. J. Org. Chem. 1981,
46, 2089. doi:10.1021/jo00323a022.
(5) (a) For reviews on ketene acetals, see: Schneider, C. In
Science of synthesis; de Meijere, A., Ed.; Georg Thieme
Verlag: Stuttgart, 2005; Vol. 24, pp. 293–322; (b) Mahrwald,
R. Chem. Rev. 1999, 99, 1095 doi:10.1021/cr980415r.
PMID:11749441.; (c) For a review on ketene O,N-acetals,
see: Kantlehner, W. In Science of synthesis; de Meijere, A.,
Ed.; Georg Thieme Verlag: Stuttgart, 2005; Vol. 24,
pp. 337–446; (d) For reviews on the chemistry of vinyl ke-
tene acetals, see: Kalesse, M. Top. Curr. Chem. 2005, 244,
43; (e) Casiraghi, G.; Zanardi, F.; Appendino, G.; Rassu, G.
Chem. Rev. 2000, 100, 1929. doi:10.1021/cr990247i. PMID:
11749280.
mp 80–82 8C (hexane). IR (neat) nmax: 3415, 1623 cm–1. H
1
NMR (500 Mz) d: 0.96 (t, J = 7.3), 1.43 (m, 1H), 1.54 (m,
1H), 1.73 (s, 3H), 2.94, 2.97 (2s, 6H), 3.16 (d, J = 6.8, 1H),
3.85 (m, 1H), 4.84 (s, 1H), 4.97 (m, 1H). 13C NMR: 10.2,
20.8, 21.2, 35.6, 37.2, 56.1, 72.8, 115.4, 140.5, 172.8. MS
m/e: 185 (M+, 13), 127 (75), 125 (100), 111(24). HR-MS
calcd.. for C10H19NO2: 185.1405 (M+). Found: 185.1416.
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Supplementary data
The experimental procedures and spectral data for the
preparation of 3, the crossover experiment of 1a and 1b, the
attempted TiCl4 mediated reaction of E-4a with benzalde-
hyde, the BF3ꢀOEt2 mediated reaction of Z-4a with benzal-
dehyde, the attempted generation of the titanium dienolate
of 1a, the attempted fluoride mediated reaction of 2a with
benzaldehyde, and the minimized structures and final Carte-
sian coordinates and energies for the calculated transition
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