Silylation-desilylation of propargyl amides: rapid synthesis of functionalised aldehydes and β-lactams

Article abstract of DOI:10.1016/j.tet.2007.04.064

Propargyl functionalised β-silylalkenals were easily prepared starting from suitable propargyl compounds by a silylformylation process. In particular the use of propargyl tosyl amides allowed the synthesis of α,β-unsaturated aldehydes through a two-step sequence of silylformylation-desilylation reactions. TBAF was employed to induce the desilylation process that was performed under very mild experimental conditions and occurred along with an elimination step of the tosylamido moiety affording 2-methylaryl-2-alkenals with good yields and stereoselectivity. When the tosyl amides were reacted with a hydrosilane in the presence of catalytic amounts of 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) α-silylmethylene-β-lactams were synthesised through a silylcarbocyclisation process. A high chemoselectivity towards the β-lactam was observed when dialkyl propargyl amides were employed. The obtained β-lactams were easily transformed into the corresponding methylaryl-β-lactams by fluoride induced aryl migration-desilylation with total retention of configuration of the migrating group and complete stereoselectivity towards the more stable β-lactam (E)-isomer.

Full text of DOI:10.1016/j.tet.2007.04.064

Tetrahedron 63 (2007) 6843–6854
Silylation–desilylation of propargyl amides: rapid synthesis of
functionalised aldehydes and b-lactams
*
Laura Antonella Aronica, Giulia Valentini, Anna Maria Caporusso and Piero Salvadori
Dipartimento di Chimica e Chimica Industriale, Universitaꢀ di Pisa, Via Risorgimento, 35, 56126 Pisa, Italy
Received 16 January 2007; revised 2 April 2007; accepted 19 April 2007
Available online 25 April 2007
Abstract—Propargyl functionalised b-silylalkenals were easily prepared starting from suitable propargyl compounds by a silylformylation
process. In particular the use of propargyl tosyl amides allowed the synthesis of a,b-unsaturated aldehydes through a two-step sequence of
silylformylation–desilylation reactions. TBAF was employed to induce the desilylation process that was performed under very mild exper-
imental conditions and occurred along with an elimination step of the tosylamido moiety affording 2-methylaryl-2-alkenals with good yields
and stereoselectivity. When the tosyl amides were reacted with a hydrosilane in the presence of catalytic amounts of 1,8-diazabicyclo[5.4.0]-
undec-7-ene (DBU) a-silylmethylene-b-lactams were synthesised through a silylcarbocyclisation process. A high chemoselectivity towards
the b-lactam was observed when dialkyl propargyl amides were employed. The obtained b-lactams were easily transformed into the corre-
sponding methylaryl-b-lactams by fluoride induced aryl migration–desilylation with total retention of configuration of the migrating group
and complete stereoselectivity towards the more stable b-lactam (E)-isomer.
Ó 2007 Published by Elsevier Ltd.
1. Introduction
hydrosilanes and with vinylsilanes, metathesis of silicon
containing olefins, silylcarbonylation and silylformylation
reactions. In the last case, treatment of terminal acetylenes
with CO and a hydrosilane usually results in the formylation
of the internal sp carbon of the triple bond and in the addition
of the silicon group to the terminal one, thus affording (Z)-b-
silylalkenals in high yields and with high degree of regio and
stereochemical control (Scheme 1, step 1).3
Although catalytic hydrosilylation1 reactions are well
known processes of industrial importance, in the last two
decades other reactions of silicon compounds promoted by
transition metal complexes have been revealed and inten-
sively developed.2 They include double silylation, dehydro-
genative coupling of hydrosilanes, coupling of olefins with
step 1:
R1
R1
TBAF
(CH2)nX
SiMe2Ar
silylformylation
(CH2)nX
Ar
(CH2)nX
R2
R2
R1
CO, Rh4(CO)12
ArMe2SiH
OHC
R2
1
OHC
step 2:
X = leaving
aryl migration
group
TBAF
R1
R2
R1 R2
(CH2)n
Ar
Ar
2
OHC
n = 2
O
O- alkylation
n = 1,3,4
C- alkylation
Scheme 1.
Keywords: Silylformylation; Silylcarbocyclisation; Desilylation; a,b-Unsaturated aldehydes; b-Lactams.
* Corresponding author. E-mail: psalva@dcci.unipi.it
0040–4020/$ - see front matter Ó 2007 Published by Elsevier Ltd.
doi:10.1016/j.tet.2007.04.064

6844
L. A. Aronica et al. / Tetrahedron 63 (2007) 6843–6854
The silylformylation reaction has been studied extensively
in the past few years since it can be easily extended to unsat-
urated compounds bearing several functional groups such as
alcohols, ethers, esters, ketones, aldehydes, halogens and
double bonds. Moreover, b-silylalkenals can be easily trans-
formed into silyl substituted dienes,4 dienones,5 a,b-unsatu-
rated ketones,6 and can be important precursors for the
synthesis of more complicated molecules via Peterson olefi-
nation,7 Nazarov type cyclopentenone annulation,8 Trost
type cyclopentane annulation,9 isomerisation of the double
bond, reduction and Wittig transformation of the carbonyl
group.10
2. Results and discussion
Initially the silylformylation reaction of propargyl com-
pounds 1–8 was considered and the principal results ob-
tained are described in Scheme 3 and summarised in Table
1. The reactions were performed in a stainless steel auto-
clave, under 30 atm of CO, in the presence of catalytic
amounts of Rh4(CO)12 (0.1–0.5 mol % with respect to the
acetylene) at 100 ꢀC. These preliminary data confirmed
that the nature of the propargylic substituents is a key ele-
ment of the process. Indeed, 3-bromopropyne 1 and sulfo-
nates 3 and 4 were completely consumed during the
reaction but the formation of unidentified decomposed mate-
rial was observed (Table 1, entries 1, 3 and 4). The propargyl
alcohol 2, the benzoate 5 and acetate 6 were successfully
converted into the corresponding b-silylalkenals (Z)-11, 14
and 15 (Table 1, entries 2, 5 and 6). As far as the propargyl
amides 7 and 8a are concerned, both tert-butoxy carbonyl
(Boc) and tosyl protections of the nitrogen atom were effec-
tive for the formation of the functionalised aldehydes (Z)-16
and (Z)-17 (Table 1, entries 7 and 8). In particular the reac-
tion of the propargyl tosyl amide was quantitative affording
the expected product in high yield (71% of pure compound).
Recently11 we observed that b-arylsilylalkenals can be re-
acted with tetrabutylammonium fluoride (TBAF) affording
2-methylaryl aldehydes in good yield. The reaction involved
the fluoride promoted 1,2-migration of the aryl group of the
silyl moiety to the adjacent carbon atom followed by a desi-
lylation step (Scheme 1, step 2). CN, OH or unsaturated
functionalities (C]C, C^C) in the u position of the alkyne
precursor were not involved in the migration step but were
directly transferred to the saturated products (Scheme 1,
step 2, route 1).12 On the contrary, when a leaving group,
such as a halide or a tosyl substituent, was situated at the
end of the hydrocarbon chain, ring closure reactions took
place with the formation of three-, five- and six-membered
ring products. Cycloalkanecarbaldehydes and 5-methyl-
aryl-3,4-dihydro-2H-pyrans were generated by intramolecu-
lar C-alkylation or O-alkylation of the carbanion formed
after the fluoride addition to the silicon atom and subsequent
aryl migration (Scheme 1, step 2, route 2).12
Considering our interest in the propargyl amides as precur-
sors of more complex compounds such as b-lactams we ex-
tended our investigations to the reactivity of tosyl amides
and arylsilanes with different steric and electronic require-
ments (Scheme 4). As can be easily deduced from the data
described in Table 2 (step 1), the silylformylation of prop-
argyl amides was appreciably affected by the structure of
the acetylenic reagents, in agreement with the results
In this paper we initially present an extension of our silyla-
tion–fluoride promoted aryl migration protocol to several
acetylenes characterised by substituents in the propargylic
position.13 Particular attention will be paid to propargyl
amides since they are useful synthetic building blocks that
can be precursors of biologically important molecules such
as b-lactams. Indeed Matsuda reported a direct synthesis
of b-lactam rings starting from propargyl amides through
a one pot base catalysed silylcarbocyclisation that requires
X
R1
+
PhMe2SiH
9a
R2
1-8
CO, 30atm
Rh4(CO)12
R1
X
(Z)-10-17
R2
OHC
SiMe2Ph
t
a sterically hindered hydrosilane such as BuMe2SiH to
succeed (Scheme 2).14
Scheme 3.
R2
R1
NHp-Ts
SiR3
CO Rh4(CO)12
R1
Table 1. Silylformylation of propargyl derivatives 1–8a with dimethylphe-
nylsilane 9aa
R3SiH
base
R2
N
p-Ts
O
Entry
Substrate
X
R1
R2
Yieldb (%)
Scheme 2.
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8a
Br
OH
H
H
H
H
Me
Me
Me
Me
H
H
H
H
H
Et
Et
H
(Z)-10
dec
(Z)-11
(Z)-12
(Z)-13
(Z)-14
(Z)-15
(Z)-16
(Z)-17
83c (71)
dec
OSO2Me
OSO2Ph
OCOPh
OCOMe
NHBoc
NH-p-Ts
It is well known that the b-lactam skeleton is the key struc-
tural unit of the most widely employed b-lactam antibiotics
and inhibitors of b-lactamase15 and can be an important in-
termediate for the synthesis of a- and b-amino acids, aspartic
acid derivatives, alkaloids, heterocycles and taxoids.16
Hence we took into account the application of the silylcarbo-
cyclisation reaction to suitable propargyl amides and aryl-
dimethylsilanes that could allow the formation of
3-(arylsilylmethylene)-b-lactams. In particular, a detailed
study of the reactivity of different arylsilanes is reported
and the application of the TBAF induced aryl migration–
desilylation step to the synthesis of functionalised b-lactams
is investigated.
decd
78 (54)
100 (75)
70 (63)
91 (71)
a
Reactions were carried out with 2 mmol of silane, 2 mmol of propargyl
substrate, 2ꢁ10ꢂ3–10ꢂ2 mmol of Rh4(CO)12, 3 mL of CH2Cl2 in a stain-
less steel autoclave under 30 atm of CO at 100 ꢀC for 24 h.
Determined by GLC of the reaction mixture after work up. The isolated
yields of pure compounds are reported in parentheses.
Reaction performed at room temperature; 17% of (E)-isomer was detected
by 1H NMR analysis.
b
c
d
When the reaction was performed at room temperature the propargyl
precursor was recovered unreacted.

L. A. Aronica et al. / Tetrahedron 63 (2007) 6843–6854
6845
R1
NHp-Ts
R1
SiMe2Ar
CHO
p-TsHN
CO, 30atm
R2
+
R1
R2
+ ArMe2SiH
9
R2
Rh4(CO)12
OHC
SiMe2Ar
(Z)-17
8
18
step 1: silylformylation
TBAF
step 2: aryl migration-
desilylation
R1
CH2 Ar
CHO
19
R2
Scheme 4.
Table 2. Silylformylation–desilylation reactions of propargyl amides 8
Entry
8
R1
R2
9
Ar
Step 1: silylformylationa
Step 2: aryl migrationb
Conv.c (%)
(Z)-17, 18d
Yieldc (%)
19
Yielde (%) (E/Z)f
(Z)-17
18d
1
2
3
4
5
a
b
c
d
e
H
H
Me
Me
Me
Me
tBu
Me
Et
a
a
a
a
a
Ph
Ph
Ph
Ph
Ph
100
73
100
79
aa
ba
ca
da
ea
91 (71)g
95 (49)g
87 (42)
80 (44)
38 (15)h
—
—
13
20
—
aa
ba
ca
da
—
52 (100/0)
45 (100/0)
75
59 (65/35)
—
tBu
53
6
7
a
c
H
Me
Me
Me
b
c
o-Me–C6H4
p-OMe–C6H4–
65
68
ab
cc
100 (38)
87 (48)
—
13
ab
cc
67 (100/0)
55
Reactions were performed with 2 mmol of silane, 2 mmol of amide, 2ꢁ10ꢂ3–10ꢂ2 mmol of Rh4(CO)12, 3 mL of CH2Cl2 in a stainless steel autoclave under
a
30 atm of CO at 100 ꢀC for 24 h.
b
Reactions were performed by adding 1 mmol of b-silylalkenals to a THF solution (10 mL) of TBAF (2.5 mmol) at room temperature; 100% conversion of the
precursors was detected by 1H NMR analyses.
c
d
e
f
Determined by GLC of the reaction mixture after work up. The isolated yields of pure compounds are reported in parentheses.
An E/Z mixture was always observed.
Yields of pure compounds.
Diastereomeric ratio was obtained by 1H NMR analysis. E and Z configurations of the products were determined by NOE experiments.
Small amounts of isomerisation byproducts were observed.
g
h
Hydrosilylated products (62%) were detected by 1H NMR analysis.
previously observed studying the reaction of nonfunctional-
with an elimination step of the tosyl amide moiety yielding
2-methylaryl-2-alkenals 19. The reaction was totally stereo-
selective when a tertiary allylic carbon was present on the
(Z)-17 precursors and the more stable isomer (E) was exclu-
sively formed (Table 2, step 2, entries 1, 2 and 6). The 1,2-
rearrangement of the aromatic ring occurred with complete
retention of the original configuration of the Ar, as observed
in the cases of ortho- and para-functionalised phenyl silanes
(Table 2, step 2, entries 6 and 7).
ised 1-alkynes.10 Indeed, the less hindered tosyl amides
reacted rapidly with almost total selectivity towards the
corresponding b-silylalkenals (Z)-17 (Table 2, step 1, entries
1 and 2). On the other hand, decreasesin both the reaction rate
and selectivity were detected when the silylformylation was
carried out on acetylenes with bulky substituents on the prop-
argyl carbon (Table 2, step 1, entries 3–5). In particular, in the
case of N-(1-tert-butyl-1-methyl-2-propynyl)-p-toluenesul-
fonamide 8e (Table 2, entry 5), the conversion after 24 h
was only 53% and the hydrosilylation reaction was highly
competitivewith the formylation one (62% vs 38%). An anal-
ogous reaction trend was observed when hindered arylsilanes
were employed: the use of ortho-tolyldimethylsilane resulted
in a significant lowering of the reaction rate with respect to
Me2PhSiH (Table 2, entry 6 vs entry 1). However, the chemo-
selectivity of the process was quite good, thus allowing the
extension of the silylformylation of propargyl amides to
functionalised hydrosilanes.
The described silylformylation–desilylation protocol repre-
sents a new simple pathway for the synthesis of a,b-
unsaturated aldehydes from propargyl tosyl amides. An
improvement of this methodology was achieved by replac-
ing the amide moiety on the acetylene precursors with a
benzoate or an acetate group. The propargyl esters can be
generally prepared by means of easy organic chemistry pro-
cedures17 starting from the corresponding alcohols (often
commercially available) thus enhancing the applicability
of the protocol. Indeed, a,b-unsaturated aldehydes 19aa
and 19da were quantitatively generated by the TBAF in-
duced reactions of b-silylalkenals (Z)-14 and (Z)-15 derived
from propargyl benzoate and propargyl acetate 5 and 6, re-
spectively (Scheme 5). As shown in Scheme 5 the presence
of a good leaving group induced the elimination step that
occurred with complete selectivity towards the (E)-isomer
in the case of benzoate (Z)-14 confirming the stereochemical
trend described in Table 2.
The obtained b-silylalkenals (Z)-17 were then submitted to
the aryl migration–desilylation process (Scheme 4, Table
2, step 2). The reactions were performed under very mild ex-
perimental conditions, adding 1 mmol of aldehyde to a THF
solution of TBAF (2.5 mmol) and hydrolysing immediately
with water. Complete consumption of the reagents was ob-
served and the products were recovered in good yields. In
this case, the 1,2-anionotropic rearrangement is coupled

6846
L. A. Aronica et al. / Tetrahedron 63 (2007) 6843–6854
R1
obtained results clearly indicated that the structure of the
OX
R1
R2
CH2 Ph
CHO
TBAF
R2
propargyl precursors played a crucial role in the selectivity
of the reaction, the presence of a bulky propargyl carbon be-
ing essential to force the closure of the ring (cf. entries 1–3
vs entries 4–9, Table 3). Moreover the high acidity of the
NH-tosyl proton seemed to be fundamental for the b-lactam
formation since the cyclisation process requires the removal
of the nitrogen proton by the base DBU.
OHC
SiMe2Ph
R1 R2
yield E/Z
n
X
Me
COPh
(Z)-19aa
(Z)-19da
100/0
69%
57/43
75%
H
(Z)-14
(Z)-15
COMe
Et
Me
Scheme 5.
This hypothesis was confirmed by the results obtained react-
ing different arylsilanes with 3-amino-3-methyl-1-pentyne
protected by a benzyl (21) or a tert-butoxy carbonyl group
(7) (Scheme 7, Table 4). It is evident from the data reported
in Table 4 that both the presence of a Boc and a CH2Ph func-
tionality on the nitrogen atom clearly favoured the silylfor-
mylation reaction that occurs without breaking of the N–H
bond (Table 4, entries 1 and 2); even the use of 1 equiv of
the base was ineffective to afford the b-lactam ring (Table
4, entry 3). In the case of the benzyl derivative 21 the b-silyl-
alkenal could not be isolated since it immediately rearranged
to the elimination product 18 (Table 4, entries 2 and 4).13,18
When different arylsilanes were tested, only MePh2SiH
showed 54% chemoselectivity towards the silylcarbo-
cyclisation process (Table 4, entry 4), while no reaction
was detected employing more hindered silanes such as
triphenylsilane 9i or ortho-tolyldimethylsilane 9b (Table 4,
entries 5 and 6).
The good results obtained both in the silylformylation and in
the desilylation processes of the tosyl amides prompted us to
explore the reactivity of such substrates in the preparation of
functionalised b-lactams through the silylcarbocyclisation–
desilylation sequence. Initially we investigated the reactivity
of N-(1-tert-butyl-2-propynyl)-p-toluene sulfonamide 8b
(Scheme 6, Table 3, entries 1–3) chosen as a model substrate.
The reactions were performed with equimolar amounts of si-
lane and amide and catalytic quantities both of Rh4(CO)12
(0.1 mol %) and of DBU (10%). The silylformylation pro-
cess was highly competitive with the silylcarbocyclisation
reaction. Only in the presence of a sterically hindered hydro-
silane such as ortho-tolyldimethylsilane (Table 3, entry 3)
a good amount of the desired b-lactam was formed, but the
reaction rate was quite slow (59% of conversion after 4 h).
This reaction trend completely changed when amides with
a quaternary a-carbon atom were employed. Indeed a high
chemoselectivity towards the b-lactam was observed when
dialkyl functionalised propargyl amides were reacted (Table
3, entries 4–9) regardless of the steric requirements of the
hydrosilanes. The use of functionalised silanes allowed the
preparation of the polyfunctionalised b-lactams 20ee–eg. It
is noteworthy that the reaction with dimethylthiophenylsi-
lane 9g determined the addition of the heteroaromatic ring
on the silylmethylene portion of the product 20eg. The
With the access to the arylmethylene b-lactams 20 in hand
we turned to the TBAF promoted aryl migration–desilyla-
tion process that would allow a very easy and direct synthe-
sis of 3-methylaryl-b-lactams. As it is shown in Scheme 8
and Table 5, azetidinones 20ca–eg were successfully reacted
with 1 equiv of TBAF affording the corresponding a-meth-
ylaryl substituted rings 23. All the reactions proceeded
with good yields of purified products. A very high
R1
N
R1
R2
NHp-Ts
SiMe2Ar
+
p-TsHN
CO, 30atm, 100°C
R2
OHC
(Z)-17
R1
+ ArMe2SiH
9
Rh4(CO)12
R2
8
SiMe2Ar
p-Ts
O
20
DBU
Scheme 6.
Table 3. Silylcarbocyclisation reactions of propargyl tosyl amides 8 with aryldimethylsilanes 9a
Entry
8
R1
R2
9
Ar–
t (h)
Conv.b (%)
20, (Z)-17
Yieldc (%)
(Z)-17
20
1
2
3
b
b
b
H
H
H
tBu
tBu
tBu
a
d
b
Ph
p-Ph–C6H4–
o-Me–C6H4–
4
4
4
54
50
59
ba
bd
bb
—
—
70 (35)
100
100 (33)
30
4
5
6
7
8
c
d
e
e
e
Me
Me
Me
Me
Me
Me
Et
a
a
a
e
f
Ph
Ph
4
4
4
6
6
100
100
100
58
ca
da
ea
ee
ef
95 (69)
96 (58)
100 (76)
100 (52)
100 (45)
5
4
—
—
—
tBu
tBu
tBu
Ph
p-Me–C6H4–
p-NMe2–C6H4–
67
9
e
Me
tBu
g
6
77
eg
100 (60)
—
S
Reactions were performed with 2 mmol of silane, 2 mmol of amide, 2ꢁ10ꢂ3 mmol of Rh4(CO)12, 0.2 mmol of DBU, 3 mL of CH2Cl2 in a stainless steel
a
autoclave under 30 atm of CO at 100 ꢀC.
Determined by GLC conversion of silane.
The isolated yields of pure compounds are reported in parentheses.
b
c

L. A. Aronica et al. / Tetrahedron 63 (2007) 6843–6854
6847
Table 4. Silylcarbocyclisation reactions of 3-amino-3-methyl-1-pentyne derivatives with arylsilanesa
Entry
Substrate
X
9
R3
Conv.b (%)
Product distributionc (%)
1
7
Boc
9a
9a
9a
9h
9i
Me2Ph
Me2Ph
Me2Ph
MePh2
Ph3
Me2(o-Me-C6H4)
100
84
0
62
0
—
22a (30)
—
22h (54)
—
—
(Z)-16 (95)
18da (70)
—
18dh (46)
—
—
2
21
21
21
21
21
CH2Ph
CH2Ph
CH2Ph
CH2Ph
CH2Ph
3d
4
5
6
9b
0
Reactions were performed with 2 mmol of silane, 2 mmol of amine derivative, 2ꢁ10ꢂ3 mmol of Rh4(CO)12, 0.2 mmol of DBU, 3 mL of CH2Cl2 in a stainless
a
steel autoclave under 30 atm of CO at 100 ꢀC.
Determined by GLC conversion of silane.
b
c
d
Determined by GLC and 1H NMR analysis; the percentage of the different products is reported in parentheses.
Reaction performed with 1 equiv of DBU (2 mmol).
Et
Me
HN
substituents on the b-lactam rings was confirmed by means
of the NOESY spectra. For instance in the cases of 4-tert-
butyl-1-azetidin-2-ones 23ea–eg, relevant NOE effects be-
tween the tert-butyl protons and the adjacent CH(CH2Ar)
hydrogen were detected in the (E)-products (i.e., tert-butyl
and CH are in a cis configuration) (Fig. 1).
+ R3SiH
9
X
CO, 30atm
Rh4(CO)12
DBU, 4h
100°C
X = BOC (7)
X = CH2Ph (21)
It is noteworthy that both the functionalised benzene rings
and the heteroaromatic thiophenyl ring were transferred
from the silicon to the carbon atom with total retention of
the initial configuration. All the observed results seemed to
indicate that the formation of the arylmethyl-b-lactams is
achieved through a reaction pathway very similar to the
one proposed for the desilylation reaction of b-silylalke-
nals.11 As shown in Scheme 9 a plausible mechanism
involves the addition of fluoride to silicon yielding a pentava-
lent Si atom (24), aryl-1,2-anionotropic rearrangement to the
adjacent carbon atom with formation of enolate 25, its pos-
sible Brook rearrangement (26, 27)19 or direct protonation
(28) and final removal of silyl moiety by water or excess
fluoride itself.
Et
Et
Me
OHC
NHBOC
SiR3
Me
Et
Me
NHCH2Ph
SiR3
N
+
SiR3
(Z)-16
PhCH2
O
OHC
22
Et
SiR3
CHO
Me
18
Scheme 7.
diastereoselectivity towards the formation of the less hin-
dered (E)-b-lactams was observed in all cases regardless
of the steric requirements of the silyl moiety of the employed
substrates (Table 5, entries 2–6). The configuration of the
H
t-Bu
Me
Ar
R1
N
R1
H
SiMe2Ar
R2
∗
R2
∗
Ar
TBAF
100%
N
p-Ts
O
N
23ea-eg
p-Ts
O
p-Ts
O
23
20
Scheme 8.
Figure 1.
Table 5. TBAF mediated aryl migration–desilylation reactions of p-Ts-b-lactams 20a
Entry
20
R1
R2
Ar
23
Yieldb (%)
Diastereoselectivityc
1
2
3
4
5
ca
da
ea
ee
ef
Me
Me
Me
Me
Me
Me
Et
Ph
Ph
ca
da
ea
ee
ef
60
58
91
82
51
—
91/9 (E/Z)
95/5 (E/Z)
100 (E)
100 (E)
tBu
tBu
tBu
Ph
p-CH3–C6H4–
p-NMe2–C6H4–
6
eg
Me
tBu
eg
63
100 (E)
S
a
Reactions were performed by adding 1 mmol of p-Ts-b-lactams to a THF solution (10 mL) of TBAF (2.5 mmol) at room temperature; 100% conversion of the
precursors was detected by 1H NMR analyses.
Yields of pure compounds.
Determined by NOESY spectral analyses.
b
c

6848
L. A. Aronica et al. / Tetrahedron 63 (2007) 6843–6854
Ar
Si
R2
(1 M in THF) were purchased from Fluka and used without
purification. Alkynes 3, 5 and 6 were prepared from the cor-
responding commercial propargyl alcohols according to lit-
erature methods.21 Rh4(CO)12 was prepared and purified as
previously reported.22 1H NMR (200 MHz) and 13C NMR
(50.3 MHz) spectra were recorded in CDCl3 solution with
Me4Si or CHCl3 as internal standard; d values are given in
parts per million and coupling constants (J) in hertz. The
Z/E configurations were determined by means of NOE
experiments. Infrared absorption spectra were recorded as
neat films. Mass spectra were obtained with a Perkin–Elmer
Q-Mass 910 connected to a Perkin–Elmer 8500 gas chro-
matograph. GLC analyses were performed with a DB1
capillary column (30 mꢁ0.52 mm, 5 mm) using He as the
carrier gas and a flame ionisation detector (FID). Column
chromatography was performed on silica gel 60 (230–400
mesh). All products were identified and characterised by
spectroscopic and analytical data.
R2
Ar
R1
Si
Me
F-
R1
F
Me
N
Me
Me
N
p-Ts
O
p-Ts
O
20
24
Ar
Ar
R2
R1
R2
R1
SiMe2F
N
26
N
p-Ts
OSiMe2F
p-Ts
O
25
H2O
Ar
Or
H2O
Ar
R2
R2
R1
R1
SiMe2F
N
N
p-Ts
OSiMe2F
p-Ts
OH
28
27
H2O or F-
R2
N
H
4.1.1. Synthesis of 3-methyl-3-(N-tert-butoxycarbonyl-
amino)-1-pentyne, 7. To a solution of 2.83 g (29.2 mmol)
of 3-amino-3-methyl-1-pentyne in 44 mL of DMF and
10 mL of triethylamine were added 12.75 g (58.4 mmol)
of di-tert-butyldicarbonate. The mixture was stirred at
50 ꢀC for 30 min and at 25 ꢀC for 24 h. The reaction mixture
was hydrolysed with water (50 mL), extracted with Et2O
(3ꢁ30 mL) and the organic layers were washed with diluted
HCl and with water until neutral pH. The solvent was re-
moved under vacuum and the crude product purified by
distillation affording 4.2 g (73% yield) of 3-methyl-3-(N-
tert-butoxycarbonylamino)-1-pentyne (colourless oil); bp
60 ꢀC (0.1 mmHg); 1H NMR d 0.96 (3H, t, J¼7.2 Hz),
1.41 (9H, s), 1.52 (3H, s), 1.60–2.00 (2H, m), 2.72 (1H, s),
4.65 (1H, s); 13C NMR d 8.6, 26.6, 28.3, 33.5, 51.1, 69.8,
79.4, 86.3, 153.9; IR n 3288, 2112, 1700, 1488, 1361,
1250, 1161. Anal. Calcd for C11H19NO2: C 66.97, H 9.71,
N 7.10; found: C 66.78, H 9.74, N 7.08.
R1
p-Ts
Ar
O
23
Scheme 9.
3. Conclusions
In conclusion we have shown that it is possible to prepare
a,b-unsaturated aldehydes and 3-methylaryl-b-lactams
from easily available propargyl amides through a two-step
protocol of silylformylation or silylcarbocyclisation–desily-
lation processes. Reaction trends are strictly influenced by
the structural features of the reagents. The substituent on
the nitrogen atom markedly affected both carbonylation re-
actions, b-silylalkenals and a-silylmethylene-b-lactams be-
ing formed in the presence of tosyl protected amines. Poorly
hindered propargyl amides reacted smoothly with different
arylsilanes and the obtained aldehydes were quantitatively
converted into the corresponding unsaturated products
with complete diastereoselectivity towards the more stable
(E) isomers. On the other hand, the cyclisation reactions re-
quired hindered substrates to occur with high chemoselectiv-
ity. The obtained b-silylmethylene-b-lactams are stable and
can be submitted to a desilylation process by treatment with
TBAF. No ring opening is observed and the aryl moiety is
transferred to the adjacent carbon atom with total retention
of its configuration thus generating 3-methylaryl azetidi-
nones that represent useful precursors to amino acid deriva-
tives and potential enzyme inhibitors.
4.1.2. General procedure for the synthesis of N-prop-
argyl-p-toluenesulfonamides 8.23 To a solution of the prop-
argylamine24 in 15% DMF–water (v/v) was added a slight
excess of p-TsCl in three portions (60%, 30%, 10% of the to-
tal, respectively). After the first addition (60%), the reaction
mixture was stirred at 50 ꢀC until the pH of the solution had
decreased to ca. 3 and was adjusted to pH 8 with 25% aque-
ous NaOH. This adjustment was followed with a second por-
tion of p-TsCl (30%). Within 20 min the pH was again ca. 3
and readjusted to pH 8 with more 25% NaOH. A final por-
tion (10%) of p-TsCl was added. After 10 min, the pH 3
solution was again adjusted to pH ca. 9 and stirred for 2 h,
during which time the pH remained approximately constant.
The reaction mixture was acidified (to pH 3) with 6 N HCl,
cooled in ice with stirring and the snow white product crys-
tals filtered, washed and recrystallised from toluene.
4. Experimental section
4.1. General remarks
4.1.2.1.
N-(1-Methyl-2-propynyl)-p-toluenesulfon-
All solvents were reagent grade materials purified by stan-
dard methods. THF was distilled from sodium, CH2Cl2
from P2O5 and DBU from KOH just before use. All silanes
9 were distilled and stored under inert gas. Noncommercial
silanes 9b–g were prepared from the corresponding
Grignard reagents according to the method described by
Hiyama and Fujita.20 Alkynes 1, 2, 4 and TBAF solution
amide (8a).25 The general procedure was followed using
25 mL of 15% DMF–water solution, 8.15 g (0.043 mol) of
p-TsCl (total amount) and 2.28 g (0.033 mol) of 3-amino-
1-butyne. After the usual work up, it gave 5.09 g (69% yield)
of N-(1-methyl-2-propynyl)-p-toluenesulfonamide as white
1
solid; mp 79–81 ꢀC; H NMR d 1.34 (3H, d, J¼6.9 Hz),
2.02 (1H, d, J¼2.2 Hz), 2.35 (3H, s), 4.02–4.18 (1H, m),

L. A. Aronica et al. / Tetrahedron 63 (2007) 6843–6854
6849
5.27 (1H, d, J¼8.4 Hz), 7.23 (2H, d, J¼8.1 Hz), 7.73 (2H, d,
J¼8.1 Hz); 13C NMR d 21.4, 23.1, 40.4, 71.7, 82.7, 127.3,
129.4, 137.2, 143.4; MS (EI) m/z (rel int.%): 208 (M+ꢂ15,
24), 155 (40), 132 (5), 91 (100), 77 (5), 68 (7), 65 (20); IR
n 3265, 2110, 1599, 1330, 1158.
MS (EI) m/z (rel int.%): 222 (M+ꢂ57, 46), 155 (63), 139
(5), 108 (3), 91 (100), 77 (5), 68 (22), 57 (7); IR (KBr) n
3302, 3256, 2124, 1597, 1321, 1157. Anal. Calcd for
C15H20NO2S: C 64.72, H 7.24, N 5.03; found: C 6.83, H
7.22, N 5.04.
4.1.2.2. N-(1-tert-Butyl-2-propynyl)-p-toluenesulfon-
amide (8b). The general procedure was followed using
10 mL of 15% DMF–water solution, 4.50 g (0.024 mol) of
p-TsCl (total amount) and 2.22 g (0.020 mol) of 3-amino-
4,4-dimethyl-1-pentyne. After the usual work up, it gave
4.12 g (78% yield) of N-(1-tert-butyl-2-propynyl)-p-tolu-
4.1.3. General procedure for the silylformylation of prop-
argyl derivatives with aryldimethylsilanes catalysed by
Rh4(CO)12. Catalytic runs were performed in a 25 mL stain-
less steel autoclave fitted with a Teflon inner crucible and
a stirring bar. In a typical run, freshly distilled CH2Cl2
(3 mL), previously degassed ArMe2SiH (2 mmol), the re-
quired propargyl derivative (2 mmol) and 2ꢁ10ꢂ3 mmol of
Rh4(CO)12 were put, under CO atmosphere, in a Pyrex
‘Schlenk’ tube. This solution was introduced in the auto-
clave, previously placed under vacuum (0.1 mmHg), by
a steel syphon. The reactor was pressurised with 30 atm
of carbon monoxide and the mixture was stirred at 100 ꢀC
for 24 h. After removal of excess CO (fume hood), the reac-
tion mixture was diluted with CH2Cl2 (10 mL), filtered
through Celite and concentrated in vacuo. The reagent con-
version and the product composition were determined by
1
enesulfonamide as white solid; mp 149–153 ꢀC; H NMR
d 0.99 (9H, s), 1.99 (1H, d, J¼2.4 Hz), 2.42 (3H, s), 3.72
(1H, dd, J¼10.2, 2.4 Hz), 5.01 (1H, d, J¼10.2 Hz), 7.29
(2H, d, J¼8.1 Hz), 7.80 (2H, d, J¼8.1 Hz); 13C NMR
d 21.5, 25.7, 35.3, 55.3, 73.2, 80.6, 127.4, 129.4, 137.2,
143.3; MS (EI) m/z (rel int.%): 208 (M+ꢂ57, 15), 155
(34), 139 (18), 110 (23), 91 (96), 65 (36), 54 (100), 41
(10); IR (KBr) n 3291, 3250, 2116, 1598, 1329, 1162.
Anal. Calcd for C14H18NO2S: C 63.61, H 6.86, N 5.30;
found: C 63.73, H 6.84, N 5.29.
1
GLC and H NMR. The purification of the crude oil by
column chromatography on silica gel afforded the pure
b-silylalkenals.
4.1.2.3. N-(1,1-Dimethyl-2-propynyl)-p-toluenesulfon-
amide (8c).14 The general procedure was followed using
50 mL of 15% DMF–water solution, 19.06 g (0.1 mol) of
p-TsCl (total amount) and 7.27 g (0.087 mol) of 3-amino-
3-methyl-1-butyne. After the usual work up, it gave
10.31 g (50% yield) of N-(1,1-dimethylpropynyl)-p-toluene-
sulfonamide as white solid; mp 118–121 ꢀC; 1H NMR d 1.55
(6H, s), 2.09 (1H, s), 2.42 (3H, s), 4.86 (1H, br s), 7.28 (2H,
d, J¼8.4 Hz), 7.82 (2H, d, J¼8.4 Hz); 13C NMR d 21.5,
30.7, 49.9, 71.2, 85.5, 127.6, 129.2, 138.9, 143.1; MS (EI)
m/z (rel int.%): 222 (M+ꢂ15, 65), 155 (81), 105 (3), 91
(100), 77 (4), 65 (16), 52 (4); IR (KBr) n 3270, 3232,
2110, 1322, 1149.
4.1.3.1. (Z)-2-(Hydroxymethyl)-3-[(dimethylphenyl)-
silyl]acrylaldehyde, (Z)-11. The crude oil was purified by
column chromatography on silica gel using hexane–
AcOEt¼90/10 as eluent (71% yield, colourless oil); 1H
NMR d 0.52 (6H, s), 2.00 (1H, s), 4.35 (2H, d, J¼1.4 Hz),
7.17 (1H, t, J¼1.4 Hz), 7.34–7.38 (3H, m), 7.49–7.53 (2H,
m), 9.78 (1H, s); 13C NMR d ꢂ0.2, 64.7, 128.8, 130.2,
134.1, 137.8, 140.5, 144.8, 193.8; IR n 3422, 3066, 2955,
2888, 2700, 1950, 1885, 1811, 1677, 1422, 1250. Anal.
Calcd for C12H16O2Si: C 65.41, H 7.32, found: C 65.24, H
7.30.
4.1.2.4. N-(1-Methyl-1-ethyl-2-propynyl)-p-toluene-
sulfonamide (8d).12 The general procedure was followed
using 30 mL of 15% DMF–water solution, 11.4 g
(0.060 mol) of p-TsCl (total amount) and 5.06 g
(0.052 mol) of 3-amino-3-methyl-1-pentyne. After the usual
work up, it gave 10.04 g (77% yield) of N-(1-methyl-1-
ethyl-2-propynyl)-p-toluenesulfonamide as white solid; mp
4.1.3.2. (Z)-3-Formyl-4-(dimethylphenylsilyl)-but-3-
en-2-yl benzoate, (Z)-14. The crude oil was purified by
column chromatography on silica gel using hexane–
AcOEt¼90/10 as eluent (54% yield, colourless oil); 1H
NMR d 0.55 (6H, s), 1.52 (3H, d, J¼6.4 Hz), 6.00 (1H, q,
J¼6.4 Hz), 7.24 (1H, s), 7.38–7.60 (8H, m), 8.04–8.12
(2H, m), 9.85 (1H, s); 13C NMR d ꢂ0.3, 20.5, 68.6, 128.2,
128.4, 129.5, 129.6, 130.2, 133.0, 133.5, 137.3, 147.2,
156.0, 165.2, 191.3; MS (EI) m/z (rel int.%): 323 (11), 261
(11), 217 (100), 218 (19), 181 (6), 139 (15), 105 (69).
Anal. Calcd for C19H20O3Si: C 70.34, H 6.21; found: C,
70.55, H 6.23.
1
92 ꢀC; H NMR d 0.97 (3H, t, J¼7.4 Hz), 1.50 (3H, s),
1.62–1.90 (2H, m), 2.09 (1H, s), 2.41 (3H, s), 5.60 (1H, br
s), 7.26 (2H, d, J¼8.4 Hz), 7.84 (2H, d, J¼8.4 Hz); 13C
NMR d 8.4, 21.4, 27.5, 35.9, 53.9, 72.5, 84.0, 127.5,
129.1, 139.2, 142.8; MS (EI) m/z (rel int.%): 222 (M+ꢂ29,
33), 155 (52), 91 (100), 89 (6), 77 (4), 65 (13); IR (KBr) n
3290, 2113, 1596, 1321, 1145.
4.1.3.3. (Z)-3-Acetoxy-3-methyl-2-[(dimethylphenyl-
silyl)methylene]pentanal, (Z)-15.12 The crude oil was
purified by column chromatography on silica gel using
hexane–AcOEt¼80/20 as eluent (75% yield, colourless
4.1.2.5. N-(1-tert-Butyl-1-methyl-2-propynyl)-p-tolu-
enesulfonamide (8e). The general procedure was followed
using 30 mL of 15% DMF–water solution, 14.45 g
(0.076 mol) of p-TsCl (total amount) and 6.39 g
(0.051 mol) of 3-amino-3,4,4-trimethyl-1-pentyne. After
the usual work up, it gave 5.69 g (40% yield) of N-(1-tert-
butyl-1-methyl-2-propynyl)-p-toluenesulfonamide as white
1
oil); H NMR d 0.62 (6H, s), 1.15 (3H, t, J¼7.5 Hz), 1.78
(3H, s), 1.96–2.08 (2H, m), 2.13 (3H, s), 6.99 (1H, s),
7.47–7.50 (3H, m), 7.62–7.80 (2H, m), 9.88 (1H, s).
1
solid; mp 125–127 ꢀC; H NMR d 0.99 (9H, s), 1.45 (3H,
4.1.3.4. (Z)-3-Methyl-2-[(dimethylphenylsilyl)methyl-
(Z)-16.12
s), 2.09 (1H, s), 2.39 (3H, s), 5.21 (1H, br s), 7.24 (2H, d,
J¼8.4 Hz), 7.80 (2H, d, J¼8.4 Hz); 13C NMR d 21.4, 22.4,
24.8, 38.8, 59.8, 73.5, 83.3, 127.7, 129.0, 138.9, 142.87;
ene]-3-(tert-butoxycarbonylamino)pentanal,
The crude product was purified by column chromatography
on silica gel with dichloromethane (63% yield, colourless

6850
L. A. Aronica et al. / Tetrahedron 63 (2007) 6843–6854
1
oil); H NMR d 0.62 (6H, s), 0.76 (3H, t, J¼7.4 Hz), 1.36
(9H, s), 1.42 (3H, s), 1.66–1.88 (2H, m), 6.91 (1H, s),
7.29–7.54 (5H, m), 9.75 (1H, s); 13C NMR d ꢂ0.4, 7.9,
23.7, 28.2, 31.7, 58.3, 79.0, 127.9, 129.2, 133.5, 138.0,
147.7, 154.3, 157.8, 192.5; IR n 3354, 2972, 2742, 1718,
1694, 1583, 1426, 1250.
4.1.3.9. (Z)-3,4,4-Trimethyl-2-[(dimethylphenylsilyl)-
methylene]-3-(p-tosylamino)pentanal, (Z)-17ea. The
crude oil was purified by column chromatography on silica
1
gel using CH2Cl2 as eluent (15% yield, colourless oil); H
NMR d 0.40 (6H, s), 0.86 (9H, s), 1.38 (3H, s), 2.35 (3H,
s), 6.56 (1H, br s), 6.85 (1H, s), 7.10–7.25 (7H, m), 7.64
(2H, d, J¼8.4 Hz), 9.62 (1H, s). Anal. Calcd for
C24H33NO3SSi: C 64.97, H 7.50, N 3.16; found: C 65.12,
H 7.52, N 3.15.
4.1.3.5. (Z)-2-[(Dimethylphenylsilyl)methylene]-3-(p-
tosylamino)butanal, (Z)-17aa. The crude oil was purified
by column chromatography on silica gel using CH2Cl2 as el-
1
uent (71% yield, colourless oil); H NMR d 0.35 (3H, s),
4.1.3.10. (Z)-2-[(Dimethyl-o-tolylsilyl)methylene]-3-
(p-tosylamino)butanal, (Z)-17ab. The crude oil was puri-
fied by column chromatography on silica gel using CH2Cl2
0.36 (3H, s), 1.23 (3H d, J¼7 Hz), 2.37 (3H, s), 4.15–4.23
(1H, dq, J¼7, 9 Hz), 5.39 (1H, d, J¼9 Hz), 6.91 (1H, s),
7.19 (2H, d, J¼8.4 Hz), 7.32–7.36 (5H, m), 7.64 (2H, d,
J¼8.4 Hz), 9.45 (1H, s); 13C NMR d ꢂ0.6, 21.5, 22.3,
53.0, 127.1, 128.2, 129.6, 129.7, 133.4, 136.8, 137.8,
143.2, 150.8, 155.1, 192.3; MS (EI) m/z (rel int.%): 372
(M+ꢂ15, 15), 292 (10), 281 (27), 230 (29), 215 (25), 198
(9), 155 (52), 141 (13), 135 (55), 105 (12), 91 (100), 77
(8); IR n 3310, 2965, 2717, 1677, 1596, 1419, 1333, 1250,
1165. Anal. Calcd for C20H25NO3SSi: C 61.98, H 6.50, N
3.61; found: C 61.78, H 6.49, N 3.62.
1
as eluent (38% yield, colourless oil); H NMR d 0.37 (6H,
s), 1.19 (3H, d, J¼4.4 Hz), 2.24 (3H, s), 2.36 (3H, s), 4.17
(1H, m), 5.17 (1H, d, J¼5.8 Hz), 6.98 (1H, s), 7.10–7.34
(6H, m), 7.60 (2H, d, J¼5.2 Hz), 9.36 (1H, s); 13C NMR
d 0.2, 1.3, 21.7, 22.5, 23.6, 52.4, 125.7, 127.3, 129.9,
130.4, 130.5, 134.3, 135.7, 138.0, 143.4, 143.5, 151.8,
155.2, 192.6. Anal. Calcd for C21H27NO3SSi: C 62.81, H
6.78, N 3.49; found: C 62.94, H 6.76, N 3.48.
4.1.3.11. (Z)-3-Methyl-2-[(dimethyl-4-methoxyphenyl-
silyl)methylene]-3-(p-tosylamino)butanal, (Z)-17cc. The
crude oil was purified by column chromatography on silica
4.1.3.6. (Z)-4,4-Dimethyl-2-[(dimethylphenylsilyl)-
methylene]-3-(p-tosylamino)pentanal, (Z)-17ba. The
1
crude oil was purified by column chromatography on silica
gel using CH2Cl2 as eluent (49% yield, colourless oil); H
gel using CH2Cl2 as eluent (48% yield, colourless oil); H
1
NMR d 0.39 (6H, s), 1.46 (6H, s), 2.40 (6H, s), 3.82 (3H,
s), 5.89 (1H, br s), 6.93 (2H, d, J¼7.8 Hz), 6.96 (1H, s),
7.21 (2H, d, J¼7.8 Hz), 7.38 (2H, d, J¼7.8 Hz), 7.64 (2H,
d, J¼7.8 Hz), 9.50 (1H, s). Anal. Calcd for C22H29NO4SSi:
C 61.22, H 6.77, N 3.25; found: C 61.33, H 6.78, N 3.26.
NMR d 0.30 (3H, s), 0.31 (3H, s), 0.83 (9H, s), 2.36 (3H,
s), 3.92 (1H, d, J¼10.0 Hz), 5.80 (1H, br s), 6.72 (1H, s),
7.16 (2H, d, J¼8.4 Hz), 7.30–7.36 (5H, m), 7.58 (2H, d,
J¼8.4 Hz), 9.36 (1H, s); MS (EI) m/z (rel int.%): 344
(M+ꢂ85, 19), 228 (100), 189 (69), 174 (27), 149 (37), 135
(19), 91 (57), 77 (3); IR n 3277, 2962, 2734, 1687, 1597,
1426, 1322, 1247, 1166.
4.1.4. General procedures for the TBAF promoted rear-
rangements of (Z)-14, (Z)-15 and (Z)-17. To a solution of
2 mmol of b-silylalkenal in 10 mL of THF were added, at
room temperature, 2 mL of TBAF (1 M in THF). The reac-
tion mixture was hydrolysed with water (15 mL), extracted
with Et2O (3ꢁ10 mL) and the organic layers were dried
over Na2SO4. After concentration under vacuum, the crude
product was purified by column chromatography on silica
gel using CH2Cl2 as eluent.
4.1.3.7. (Z)-3-Methyl-2-[(dimethylphenylsilyl)methyl-
ene]-3-(p-tosylamino)butanal, (Z)-17ca. The crude oil was
purified by column chromatography on silica gel using
CH2Cl2 as eluent (42% yield, colourless oil); 1H NMR
d 0.37 (6H, s), 1.44 (6H, s), 2.37 (3H, s), 5.81 (1H, s), 6.93
(1H, s), 7.17 (2H, d, J¼8.3 Hz), 7.36–7.41 (5H, m), 7.60
(2H, d, J¼8.3 Hz), 9.45 (1H, s); 13C NMR d ꢂ0.4, 21.5,
28.2, 58.0, 127.5, 128.2, 129.4, 129.7, 133.4, 137.0, 138.9,
143.0, 149.7, 157.6, 193.2; MS (EI) m/z (rel int.%): 306
(M+ꢂ95, 17), 230 (42), 228 (22), 215 (23), 212 (76), 155
(69), 153 (15), 149 (24), 135 (36), 91 (100). Anal. Calcd
for C21H27NO3SSi: C 62.81, H 6.78, N 3.49; found: C
62.96, H 6.80, N 3.48.
4.1.4.1. (E)-2-Benzylbut-2-enal, (E)-19aa. Yield 52%
1
(colourless oil); H NMR d 2.11 (3H, d, J¼7.2 Hz), 3.71
(2H, s), 6.79 (1H, q, J¼7.2 Hz), 7.22–7.36 (5H, m), 9.53
(1H, s); 13C NMR d 15.1, 29.3, 126.0, 128.2, 128.3, 138.9,
143.5, 150.9, 194.4; MS (EI) m/z (rel int.%): 160 (M+, 82),
159 (35), 145 (100), 131 (35), 130 (45), 115 (49), 91 (88),
77 (5), 65 (24), 51 (24), 39 (22); IR n 3023, 2924, 2718,
1682. Anal. Calcd for C11H12O: C 82.46, H 7.55; found: C
82.76, H 7.58.
4.1.3.8. (Z)-3-Methyl-2-[(dimethylphenylsilyl)methyl-
ene]-3-(p-tosylamino)pentanal, (Z)-17da. The crude oil
was purified by column chromatography on silica gel using
CH2Cl2 as eluent (44% yield, colourless oil); 1H NMR d 0.48
(6H, s), 0.80 (3H, t, J¼7 Hz), 1.51 (3H, s), 1.68–1.99 (2H,
m), 2.47 (3H, s), 5.88 (1H, s), 6.98 (1H, s), 7.27 (2H, d,
J¼8.2 Hz), 7.45–7.52 (5H, m), 7.71 (2H, d, J¼8.2 Hz),
9.54 (1H, s); 13C NMR d ꢂ0.5, ꢂ0.4, 8.1, 21.4, 22.1, 33.9,
61.5, 127.4, 128.2, 129.3, 129.6, 133.4, 137.1, 139.1,
142.9, 151.3, 156.4, 193.1; MS (EI) m/z (rel int.%): 306
(M+ꢂ95, 17), 230 (42), 228 (22), 215 (23), 212 (76), 155
(69), 153 (15), 149 (24), 135 (36), 91 (100). Anal. Calcd
for C22H29NO3SSi: C 63.58, H 7.03, N 3.37; found: C
63.45, H 7.01, N 3.36.
4.1.4.2. (E)-2-Benzyl-4,4-dimethylpenten-2-al, (E)-
1
19ba.12 Yield 45% (colourless oil); H NMR d 1.20 (9H,
s), 3.80 (2H, s), 6.58 (1H, s), 7.10–7.35 (5H, m), 9.41 (1H,
s); 13C NMR d 26.4, 29.5, 30.1, 125.9, 127.9, 128.3, 139.2,
139.3, 166.0, 196.4; MS (EI) m/z (rel int.%): 202 (M+, 36),
187 (8), 159 (40), 145 (32), 131 (53), 115 (37), 91 (85), 77
(8), 65 (16), 55 (23), 51 (30), 43 (40), 41 (100), 39 (89);
IR n 3025, 2959, 2708, 1685, 1632.
4.1.4.3. 2-Benzyl-3-methylbut-2-enal, 19ca. Yield 75%
(colourless oil); 1H NMR d 2.09 (3H, s), 2.34 (3H, s), 3.77

L. A. Aronica et al. / Tetrahedron 63 (2007) 6843–6854
6851
(2H, s), 7.20–7.37 (5H, m), 10.32 (1H, s); 13C NMR d 19.4,
23.8, 30.7, 125.7, 128.1, 128.2, 135.9, 140.0, 156.7, 190.5;
MS (EI) m/z (rel int.%): 174 (M+, 93), 159 (100), 131
(31), 129 (24), 128 (24), 115 (27), 91 (73), 68 (25), 51
(20); IR n 2921, 2756, 1663, 1626. Anal. Calcd for
C12H14O: C 82.72, H 8.10; found: C 82.70, H 8.08.
oil); 1H NMR d 0.34 (6H, s), 0.97 (9H, s), 2.35 (3H, s), 3.98
(1H, m), 5.96 (1H, m), 6.81 (1H, s), 7.15–7.84 (13H, m),
9.40 (1H, s). Anal. Calcd for C29H35NO3SSi: C 68.87, H
6.98, N 2.77; found: C 69.04, H 6.99, N 2.78.
4.1.5.2.
(Z)-4,4-Dimethyl-2-[(o-tolyldimethylsilyl)-
methylene]-3-(p-tosylamino)-pentanal, (Z)-17bb. Yield
15% (colourless oil); 1H NMR d 0.36 (3H, s), 0.38 (3H, s),
1.00 (9H, s), 2.30 (3H, s), 2.43 (3H, s), 3.73 (1H, d,
J¼10.3 Hz), 5.22 (NH, d, J¼10.3 Hz), 7.0 (1H, s), 7.12–
7.40 (5H, m), 7.65 (2H, d, J¼8.4 Hz), 7.82 (2H, d,
J¼8.4 Hz), 9.37 (1H, s); 13C NMR d 0.0, 21.3, 21.4, 25.7,
35.3, 55.2, 125.3, 127.1, 127.4, 129.3, 129.4, 130.0, 130.1,
134.0, 135.1, 137.2, 142.9, 143.3, 192.4. Anal. Calcd for
C24H33NO3SSi: C 64.97, H 7.50, N 3.16; found: C 65.09,
H 7.48, N 3.15.
4.1.4.4. (E)-2-Benzyl-3-methylpenten-2-al, (E)-19da.12
1H NMR d 1.08 (3H, J¼7.8 Hz), 2.31 (3H, s), 2.41 (2H, q,
J¼7.8 Hz), 3.75 (2H, s), 7.19–7.35 (5H, m), 10.31 (1H, s);
13C NMR d 11.6, 16.7, 30.1, 30.3, 125.7, 128.0, 128.2,
135.0, 140.3, 161.5, 191.3; MS (EI) m/z (rel int.%): 188
(M+, 43), 173 (5), 159 (77), 141 (13), 131 (42), 129 (28),
115 (33), 105 (18), 91 (91), 77 (19), 65 (27), 51 (44), 43
(44), 41 (88), 39 (100).
4.1.4.5. (Z)-2-Benzyl-3-methylpenten-2-al, (Z)-19da.12
1H NMR d 1.26 (3H, t, J¼7.6 Hz), 2.07 (3H, s), 2.74 (2H, q,
J¼7.6 Hz), 3.73 (2H, s), 7.19–7.35 (5H, m), 10.28 (1H, s);
13C NMR d 14.2, 21.5, 26.2, 30.7, 125.7, 128.0, 128.2,
135.3, 139.9, 162.6, 190.2; MS (EI) m/z (rel int.%): 188
(M+, 48), 159 (74), 141 (13), 131 (42), 129 (26), 128 (26),
117 (26), 115 (31), 105 (17), 91 (89), 77 (19), 67 (26), 65
(27), 53 (25), 51 (44), 46 (45), 41 (40), 39 (100); IR n
3021, 2965, 2756, 1660, 1616.
4.1.5.3. (Z)-4-tert-Butyl-3-[(o-tolyldimethylsilyl)-
methylene]-1-(p-tosyl)-1-azetidin-2-one, (Z)-20bb. Yield
1
35% (white solid); mp 99–101 ꢀC; H NMR d 0.49 (3H,
s), 0.51 (3H, s), 0.94 (9H, s), 2.30 (3H, s), 2.41 (3H, s),
4.22 (1H, d, J¼1.4 Hz), 6.31 (1H, d, J¼1.4 Hz), 7.10–7.24
(4H, m), 7.29 (2H, d, J¼7.6 Hz), 7.82 (2H, d, J¼7.6 Hz);
13C NMR d ꢂ1.8, ꢂ1.5, 21.6, 22.9, 26.2, 34.4, 74.1,
125.0, 127.4, 129.7, 129.8, 134.0, 134.6, 135.2, 136.2,
139.8, 143.2, 144.7, 150.6, 161.1. Anal. Calcd for
C28H31NO3SSi: C 68.67, H 6.38, N 2.86; found: C 68.82,
H 6.39, N 2.85.
4.1.4.6. (E)-2-(2-Methylbenzyl)but-2-enal, (E)-19ab.
Yield 67% (colourless oil); 1H NMR d 1.90 (3H, d,
J¼7.5 Hz), 2.31 (3H, s), 3.55 (2H, s), 6.80 (1H, q,
J¼7.5 Hz), 7.03–7.09 (5H, m), 9.46 (1H, s); 13C NMR
d 15.4, 20.0, 26.9, 126.2, 126.3, 127.4, 130.3, 136.5,
136.6, 143.2, 151.8, 194.6. Anal. Calcd for C12H14O: C
82.72, H 8.10; found: C 82.70, H 8.08.
4.1.5.4. (Z)-4,4-Dimethyl-3-[(dimethylphenylsilyl)-
methylene]-1-(p-tosyl)-1-azetidin-2-one, (Z)-20ca. Yield
1
69% (white solid); mp 98 ꢀC; H NMR d 0.48 (6H, s),
1.54 (6H, s), 2.41 (3H, s), 6.14 (1H, s), 7.28–7.38 (5H, m),
7.50 (2H, m), 7.90 (2H, m); 13C NMR d ꢂ2.4, 21.6, 24.8,
71.6, 127.2, 128.0, 129.4, 129.8, 132.9, 133.6, 137.0,
137.5, 144.8, 158.9; MS (EI) m/z (rel int.%): 399 (M+, 1),
385 (6), 323 (5), 244 (19), 229 (9), 213 (3), 187 (7), 155
(27), 135 (81), 105 (14), 91 (100), 75 (7), 65 (16); IR n
1766, 1597, 1428, 1354, 1244, 1166. Anal. Calcd for
C21H25NO3SSi: C 63.12, H 6.31, N 3.51; found: C 62.90,
H 6.33, N 3.50.
4.1.4.7.
2-(4-Methoxy-benzyl)-3-methylbut-2-enal,
1
(Z)-19cc. Yield 55% (colourless oil); H NMR d 1.99 (3H,
s), 2.31 (3H, s), 3.59 (2H, s), 3.75 (3H, s), 6.77 (2H, d,
J¼7.8 Hz), 6.89 (2H, d, J¼7.8 Hz), 7.05 (2H, d,
J¼7.8 Hz), 7.24 (2H, d, J¼7.8 Hz), 10.20 (1H, s); 13C
NMR d 19.4, 28.9, 29.8, 55.1, 113.6, 129.3, 132.0, 135.3,
136.2, 157.6, 190.6. Anal. Calcd for C12H14O2: C 75.76,
H 7.42; found: C 75.45, H 7.38.
4.1.5.5. (Z)-4-Ethyl-4-methyl-3-[(dimethylphenyl-
silyl)methylene]-1-(p-tosyl)-1-azetidin-2-one, (Z)-20da.
4.1.5. General procedure for the synthesis of a-silyl-
methylene-b-lactams. Catalytic runs were performed in
a 25 mL stainless steel autoclave fitted with a Teflon inner
crucible and a stirring bar. In a typical run, 2 mmol of N-
(propargyl)-p-toluenesulfonamide, 3 mL of freshly distilled
CH2Cl2, 2 mmol of ArMe2SiH, 0.2 mmol of DBU and
2ꢁ10ꢂ3 mmol of Rh4(CO)12 were put, via syringe and under
CO atmosphere, in a Pyrex Schlenk tube. This solution was
introduced in the autoclave, previously placed under vacuum
(0.1 mmHg), by a steel syphon. The reactor was pressurised
to 30 atm of CO and stirred at 100 ꢀC for 4 h. The autoclave
was then cooled to room temperature and the excess of CO
was removed (fume hood). The reaction mixture was diluted
with CH2Cl2, filtered through silica gel (CH2Cl2 as eluent),
concentrated under reduced pressure and recrystallised
from hexane. The reagent conversion and the product compo-
sition were determined by GLC and 1H NMR.
1
Yield 58% (white solid); mp 92 ꢀC; H NMR d 0.49 (6H,
s), 0.81 (1H, t, J¼7.3 Hz), 1.54 (3H, s), 1.83 (1H, dq,
J¼21.8, 7.3 Hz), 2.02 (1H, dq, J¼21.8, 7.3 Hz), 2.43 (3H,
s), 6.11 (1H, s), 7.30–7.38 (5H, m), 7.47–7.53 (2H, m),
7.92 (2H, d, J¼8.3 Hz); 13C NMR d ꢂ2.4, ꢂ2.3, 8.6, 21.7,
23.6, 30.3, 75.7, 127.3, 128.0, 129.4, 129.8, 133.1, 133.6,
133.8, 137.4, 144.8, 157.0, 159.2; MS (EI) m/z (rel int.%):
384 (M+ꢂ29, 1), 279 (73), 217 (43), 201 (65), 188 (26),
173 (35), 155 (6), 143 (48), 142 (39), 135 (95), 115 (41),
105 (100), 91 (42), 83 (76), 75 (96), 59 (15), 43 (12); IR
n 1764, 1596, 1428, 1354, 1250, 1165. Anal. Calcd for
C22H27NO3SSi: C 63.89, H 6.58, N 3.39; found C 63.65,
H 6.56, N 3.38.
4.1.5.6. (Z)-4-Methyl-4-tert-butyl-3[(dimethylphenyl-
silyl)methylene]-1-(p-tosyl)-1-azetidin-2-one, (Z)-20ea.
1
Yield 76% (white solid); mp 97 ꢀC; H NMR d 0.48 (3H,
4.1.5.1. (Z)-4,4-Dimethyl-2-(dimethylbiphenylsilyl)-3-
(p-tosylamino)-pentanal, (Z)-17bd. Yield 33% (colourless
s), 0.49 (3H, s), 0.98 (9H, s), 1.68 (3H, s), 2.43 (3H, s),
6.18 (1H, s), 7.30–7.36 (5H, m), 7.37–7.53 (2H, m), 7.92

6852
L. A. Aronica et al. / Tetrahedron 63 (2007) 6843–6854
(2H, d, J¼8.3 Hz); 13C NMR d ꢂ2.5, ꢂ2.3, 19.1, 21.6, 26.4,
27.7, 83.8, 127.5, 127.9, 129.3, 129.6, 133.6, 134.4, 137.4,
144.6, 157.6, 160.6; MS (EI) m/z (rel int.%): 425 (M+ꢂ16,
4), 279 (73), 217 (49), 201 (74), 188 (30), 155 (5), 145
(54), 135 (78), 105 (100), 91 (28), 77 (91), 75 (95), 61
(16), 59 (18), 53 (24); IR n 1761, 1596, 1427, 1359, 1245,
1168. Anal. Calcd for C24H31NSO3Si: C 65.27, H 7.07, N
3.17; found: C 65.43, H 7.08, N 3.18.
68.4, 121.9, 127.6, 127.8, 128.6, 129.3, 134.6, 134.7,
136.5, 136.9, 162.9, 163.0; MS (EI) m/z (rel int.%): 396
(M+ꢂ15, 1), 334 (21), 197 (25), 137 (8), 105 (13), 91
(100), 77 (3), 53 (8), 43 (10); IR n 3066, 2968, 1739,
1456, 1252. Anal. Calcd for C27H29NOSi: C 78.79, H
7.10, N 3.40; found: C 78.64, H 7.12, N 3.41.
4.1.5.12. (Z)-3-Methyl-2-[(dimethylphenylsilyl)methyl]-
2-pentenal, (Z)-18da. Colourless liquid; 1H NMR
d 0.27 (6H, s), 0.94 (3H, t, J¼7.4 Hz), 1.99 (2H, s), 2.03
(2H, q, J¼7.4 Hz), 2.13 (3H, s), 7.15–7.62 (5H, m), 10.14
(1H, s); 13C NMR d ꢂ2.5, 14.6, 15.1, 23.3, 29.9, 127.6,
128.0, 128.9, 133.5, 139.0, 156.4, 191.1; MS (EI) m/z (rel
int.%): 246 (M+, 1), 231 (13), 217 (19), 137 (16), 136
(14), 135 (100), 105 (11), 43 (42), 41 (23), 39 (16). Anal.
Calcd for C15H22OSi: C 73.11, H 9.00; found: C 73.25, H
8.98.
4.1.5.7. (Z)-4-Methyl-4-tert-butyl-3-[(dimethyl-p-tolyl-
silyl)methylene]-1-(p-tosyl)-1-azetidin-2-one, (Z)-20ee.
1
Yield 52% (white solid); mp 98–100 ꢀC; H NMR d 0.49
(3H, s), 0.50 (3H, s), 1.01 (9H, s), 1.70 (3H, s), 2.35 (3H,
s), 2.45 (3H, s), 6.19 (1H, s), 7.17 (2H, d, J¼7.6 Hz), 7.34
(2H, d, J¼8.1 Hz), 7.41 (2H, d, J¼7.6 Hz), 7.96 (2H, d,
J¼8.1 Hz); 13C NMR d ꢂ2.4, ꢂ2.2, 19.1, 21.4, 21.6, 26.4,
37.7, 83.8, 127.5, 128.8, 129.6, 133.0, 133.6, 134.7, 137.4,
139.3, 144.6, 157.4, 160.6; IR n 3066, 2967, 1770, 1448,
1357, 1245, 1171. Anal. Calcd for C25H33NO3SSi: C
65.89, H 7.30, N 3.07; found: C 66.07, H 7.31, N 3.06.
4.1.5.13. (E)-3-Methyl-2-[(dimethylphenylsilyl)methyl]-
2-pentenal, (E)-18da. Colourless liquid; H NMR d 0.28
1
(6H, s), 1.09 (3H, t, J¼7.4 Hz), 1.67 (3H, s), 1.97 (2H, s),
2.55 (2H, q, J¼7.4 Hz), 7.15–7.62 (5H, m), 10.10 (1H, s).
Anal. Calcd for C15H22OSi: C 73.11, H 9.00; found: C
73.23, H 9.01.
4.1.5.8. (Z)-4-Methyl-4-tert-butyl-3-[(dimethyl-p-di-
methylaminophenylsilyl)methylene]-1-(p-tosyl)-1-azeti-
din-2-one, (Z)-20ef. Yield 45% (white solid); mp 103–
105 ꢀC; 1H NMR d 0.44 (6H, s), 0.97 (9H, s), 1.66 (3H, s),
2.42 (3H, s), 2.94 (6H, s), 6.18 (1H, s), 6.68 (2H, d,
J¼8.4 Hz), 7.25–7.38 (4H, m), 7.93 (2H, d, J¼8.4 Hz);
13C NMR d ꢂ2.3, ꢂ2.1, 19.1, 21.6, 26.3, 37.6, 40.1, 83.6,
111.9, 127.5, 129.1, 129.6, 134.7, 135.8, 137.5, 138.9,
144.6, 156.6, 160.7. Anal. Calcd for C26H36N2O3SSi: C
64.42, H 7.49, N 5.78; found: C 64.53, H 7.50, N 5.80.
4.1.5.14. (Z)-3-Methyl-2-[(methyldiphenylsilyl)methyl]-
2-pentenal, (Z)-18dh. Colourless liquid; H NMR d 0.46
1
(3H, s), 0.78 (3H, t, J¼7.4 Hz), 1.85 (2H, q, J¼7.4 Hz),
2.06 (3H, s), 2.30 (2H, s), 7.32–7.56 (10H, m), 10.07 (1H,
s); 13C NMR d ꢂ3.6, 13.2, 13.6, 16.3, 29.9, 127.7, 129.7,
133.0, 134.5, 136.9, 157.1, 191.1; MS (EI) m/z (rel int.%):
308 (M+, 0.3), 307 (M+ꢂH, 0.4), 279 (9), 231 (10), 197
(100), 181 (8), 165 (7), 137 (26), 119 (9), 105 (23), 93
(10), 53 (18), 43 (29). Anal. Calcd for C20H24OSi: C
77.87, H 7.84; found: C 77.97, H 7.82.
4.1.5.9. (Z)-4-Methyl-4-tert-butyl-3-[(dimethyl-a-thi-
enylsilyl)methylene]-1-(p-tosyl)-1-azetidin-2-one,
(Z)-
20eg. Yield 60% (white solid); mp 110 ꢀC; 1H NMR
d 0.54 (3H, s), 0.56 (3H, s), 1.02 (9H, s), 1.71 (3H, s), 2.43
(3H, s), 6.21 (1H, s), 7.17 (1H, dd, J¼4.8, 3.2 Hz), 7.30
(1H, dd, J¼3.2, 0.6 Hz), 7.33 (2H, d, J¼8.4 Hz), 7.59 (1H,
dd, J¼4.8, 0.6 Hz), 7.95 (2H, d, J¼8.4 Hz); 13C NMR
d ꢂ1.3, ꢂ1.1, 18.9, 21.5, 26.3, 37.6, 83.8, 127.4, 128.2,
129.5, 131.1, 133.5, 135.0, 136.5, 137.2, 144.6, 157.6,
160.4. Anal. Calcd for C22H29NS2O3Si: C 59.02, H 6.53,
N 3.13; found: C 58.88, H 6.55, N 3.12.
4.1.5.15. (E)-3-Methyl-2-[(methyldiphenylsilyl)methyl]-
2-pentenal, (E)-18dh. Colourless liquid; H NMR d 0.48
1
(3H, s), 0.99 (3H, t, J¼7.4 Hz), 1.50 (3H, s), 2.27 (2H, s),
2.48 (2H, q, J¼7.4 Hz), 7.32–7.56 (10H, m), 10.03 (1H,
s); 13C NMR d ꢂ3.5, 11.1, 14.5, 21.7, 26.1, 127.7, 129.2,
133.4, 134.4, 134.5, 158.3, 190.1. Anal. Calcd for
C20H24OSi: C 77.87, H 7.84; found C 77.75, H 7.81.
4.1.5.10. (Z)-1-Benzyl-3-[(dimethylphenylsilyl)methyl-
ene]-4-ethyl-4-methyl-1-azetidin-2-one, (Z)-22a. Yield
18% (thick oil); 1H NMR d 0.57 (6H, s), 0.72 (3H, t,
J¼7.2 Hz), 1.17 (3H, s), 1.55 (2H, q, J¼7.2 Hz), 4.40 (2H,
2d, J¼15 Hz), 5.78 (1H, s), 7.20–7.70 (10H, m); 13C NMR
d ꢂ2.0, ꢂ1.9, 8.5, 22.4, 29.2, 43.4, 68.2, 124.2, 127.5,
127.6, 127.8, 128.5, 129.0, 133.7, 136.9, 138.5, 161.5,
163.3; MS (EI) m/z (rel int.%): 349 (M+, 1), 348 (M+ꢂH,
1), 334 (M+ꢂ15, 24), 320 (9), 272 (19), 135 (39), 91
(100); IR n 3064, 2962, 1738, 1455, 1379, 1248, 1113.
Anal. Calcd for C22H27NOSi: C 75.59, H 7.79, N 4.01;
found: C 75.70, H 7.77, N 4.02.
4.1.6. General procedures for the TBAF promoted rear-
rangements of (Z)-20. To a solution of 2 mmol of (Z)-20 in
10 mL of THF was added, at room temperature, 2 mL of
TBAF (1 M in THF). The reaction mixture was hydrolysed
with water (20 mL), extracted with Et2O (3ꢁ10 mL) and
the organic layers were dried over Na2SO4. After concentra-
tion under vacuum, the crude product was purified by col-
umn chromatography on silica gel using CH2Cl2 as eluent.
4.1.6.1. 3-Benzyl-4,4-dimethyl-1-(p-tosyl)-1-azetidin-
2-one, 23ca. Yield 60% (thick oil); H NMR d 1.55 (3H,
1
s), 1.62 (3H, s), 2.50 (3H, s), 2.85 (1H, dd, J¼15, 9.2 Hz),
3.14 (1H, dd, J¼15, 6.6 Hz), 3.33 (1H, dd, J¼9.2, 6.6 Hz),
7.18–7.38 (5H, m), 7.40 (2H, d, J¼8.4 Hz), 7.97 (2H, d,
J¼8.4 Hz); 13C NMR d 21.6, 21.7, 27.3, 30.5, 60.2, 66.9,
126.6, 127.2, 128.2, 128.6, 129.8, 137.2, 137.5, 144.9,
166.2; IR n 2978, 1782, 1358, 1165. Anal. Calcd for
C19H21NO3S: C 66.45, H 6.16, N 4.08; found: C 66.58, H
6.17, N 4.09.
4.1.5.11. (Z)-1-Benzyl-3-[(methyldiphenylsilyl)methyl-
ene]-4-ethyl-4-methyl-1-azetidin-2-one, (Z)-22h. Yield
21% (thick oil); 1H NMR d 0.09 (3H, s), 0.76 (3H, t,
J¼7.2 Hz), 1.21 (3H, s), 1.54–1.66 (2H, m), 4.32 (1H, d,
J¼15.3 Hz), 4.50 (1H, d, J¼15.3 Hz), 6.00 (1H, s), 7.20–
7.65 (15H, m); 13C NMR d ꢂ3.1, 8.5, 22.6, 29.2, 43.5,

L. A. Aronica et al. / Tetrahedron 63 (2007) 6843–6854
6853
527–538; Marciniec, B. Silicon Chem. 2002, 1, 155–174;
Marciniec, B. Coord. Chem. Rev. 2005, 249, 2374–2390;
Trost, B. M.; Ball, Z. T. Synthesis 2005, 853–887.
4.1.6.2. (E)-3-Benzyl-4-ethyl-4-methyl-1-(p-tosyl)-1-
azetidin-2-one, (E)-23da. Yield 58% (thick oil); H NMR
1
d 0.75 (3H, t, J¼7.4 Hz), 1.57 (3H, s), 1.71–1.89 (1H, m),
1.99–2.14 (1H, m), 2.51 (3H, s), 2.79 (1H, dd, J¼14.6,
8.6 Hz), 3.14 (1H, dd, J¼14.6, 6.6 Hz), 3.32 (1H, dd,
J¼8.8, 6.6 Hz), 7.20–7.38 (5H, m), 7.40 (2H, d,
J¼8.0 Hz), 7.99 (2H, d, J¼8.0 Hz); 13C NMR d 8.5, 19.4,
21.5, 30.8, 32.4, 57.7, 70.7, 126.6, 127.2, 128.4, 128.6,
129.7, 137.2, 137.7, 144.8, 166.3; IR n 2969, 1781, 1357,
1163. Anal. Calcd for C20H23NO3S: C 67.20, H 6.49,
N 3.92; found: C 67.06, H 6.47, N 3.91.
2. For recent reviews see: Corey, J. Y.; Braddock-Wilking, J.
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4.1.6.3.
(E)-3-Benzyl-4-tert-butyl-4-methyl-1-(p-to-
1
syl)-1-azetidin-2-one, (E)-23ea. Yield 91% (thick oil); H
NMR d 0.98 (9H, s), 1.69 (3H, s), 2.51 (3H, s), 2.75 (1H,
dd, J¼14.4, 7 Hz), 3.09 (1H, dd, J¼14.4, 8.2 Hz), 3.42
(1H, dd, J¼8.2, 7 Hz), 7.25–7.35 (5H, m), 7.40 (2H, d,
J¼8.6 Hz), 8.01 (2H, d, J¼8.6 Hz); 13C NMR d 16.2, 21.6,
25.8, 31.3, 37.0, 55.9, 78.6, 126.7, 127.7, 128.6, 128.8,
129.6, 136.9, 138.0, 144.8, 167.7; IR n 2958, 1773, 1356,
1167. Anal. Calcd for C22H27NO3S: C 68.54, H 7.06, N
3.63; found: C 68.33, H 7.04, N 3.62.
4.1.6.4. (E)-3-(4-Methylbenzyl)-4-tert-butyl-4-methyl-
1-(p-tosyl)-1-azetidin-2-one, (E)-23ee. Yield 82% (thick
oil); 1H NMR d 0.93 (9H, s), 1.61 (3H, s), 2.29 (3H, s), 2.43
(3H, s), 2.65 (1H, dd, J¼14.2, 6.6 Hz), 2.97 (1H, dd,
J¼14.2, 8.2 Hz), 3.34 (1H, dd, J¼8.2, 6.6 Hz), 7.09 (4H, m),
7.32 (2H, d, J¼8.2 Hz), 7.94 (2H, d, J¼8.2 Hz); 13C NMR
d 16.1, 20.8, 21.5, 25.6, 30.7, 36.8, 55.9, 78.4, 127.5, 128.6,
129.1, 129.5, 134.8, 136.0, 136.8, 144.7, 167.6; IR n 2964,
1774, 1379, 1357, 1171. Anal. Calcd for C23H29NO3S: C
69.14, H 7.32, N 3.51; found: C 69.27, H 7.34, N 3.52.
4.1.6.5. (E)-3-[4-(Dimethylamino)benzyl]-4-tert-butyl-
4-methyl-1-(p-tosyl)-1-azetidin-2-one, (E)-23ef. Yield
51% (thick oil); 1H NMR d 0.91 (9H, s), 1.60 (3H, s), 2.43
(3H, s), 2.58 (1H, dd, J¼14.4, 7.0 Hz), 2.89 (6H, s), 2.96
(1H, dd, J¼14.4, 7.0 Hz), 3.26–3.34 (1H, m), 6.63 (2H, d,
J¼8.8 Hz), 7.05 (2H, d, J¼8.8 Hz), 7.32 (2H, d,
J¼8.3 Hz), 7.93 (2H, d, J¼8.3 Hz); 13C NMR d 16.2, 21.6,
25.8, 30.3, 36.9, 40.6, 56.3, 78.6, 112.8, 125.6, 127.6,
129.4, 129.6, 137.0, 144.7, 149.4, 168.0; IR n 2960, 1771,
1380, 1354, 1168. Anal. Calcd for C24H32N2O3S: C 67.26,
H 7.53, N 6.54; found: C 69.13, H 7.51, N 6.53.
4.1.6.6. (E)-4-tert-Butyl-4-methyl-3-[(thiophen-2-yl)-
methyl]-1-(p-tosyl)-1-azetidin-2-one, (E)-23eg. Yield
60% (thick oil); 1H NMR d 0.93 (9H, s), 1.62 (3H, s), 2.43
(3H, s), 2.95 (1H, dd, J¼15.4, 7.4 Hz), 3.18 (1H, J¼15.4,
7.4 Hz), 3.37 (1H, t, J¼7.4 Hz), 6.67–6.92 (2H, m), 7.10–
7.13 (1H, m), 7.33 (2H, d, J¼8.3 Hz), 7.93 (2H, d,
J¼8.3 Hz); 13C NMR d 16.0, 21.6, 25.4, 25.7, 37.0, 56.1,
78.7, 124.1, 126.1, 127.1, 127.7, 129.6, 136.8, 140.0,
144.9, 167.0; IR n 2960, 1773, 1380, 1356, 1170. Anal.
Calcd for C20H25NO3S2: C 61.35, H 6.44, N 6.58; found:
C 67.44, H 6.48, N 6.60.
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