Synthesis of organotin derivatives of optically active eleven-membered macrodiolides

Article abstract of DOI:10.1016/j.tetasy.2016.02.014

The synthesis and the results obtained in the hydrostannation of eight new TADDOL diacrylates and methacrylates are reported. The addition of triorganotin hydrides, R₃SnH, 12-14 (R = nBu, neophyl, Ph, respectively) to diesters 6-11 containing different combinations of substituents at the C-2 carbon of the dioxolane ring, led to macrocyclization products in all cases. The cyclohydrostannation of diacrylate 10 proceeded with complete diastereoselectivity. The cyclohydrostannation of diesters 33 and 34 with hydrides 12 and 14 in all cases only afforded one stannylated macrocycle.

Full text of DOI:10.1016/j.tetasy.2016.02.014

Tetrahedron: Asymmetry xxx (2016) xxx–xxx
Contents lists available at ScienceDirect
Tetrahedron: Asymmetry
journal homepage: www.elsevier.com/locate/tetasy
Synthesis of organotin derivatives of optically active
eleven-membered macrodiolides
⇑
Jimena Scoccia, Darío César Gerbino, Julio César Podestá
Departamento de Química e INQUISUR (UNS/CONICET), Universidad Nacional del Sur, Avda. Alem 1253, Bahía Blanca 8000, Argentina
a r t i c l e i n f o
a b s t r a c t
Article history:
The synthesis and the results obtained in the hydrostannation of eight new TADDOL diacrylates and
methacrylates are reported. The addition of triorganotin hydrides, R3SnH, 12–14 (R = nBu, neophyl, Ph,
respectively) to diesters 6–11 containing different combinations of substituents at the C-2 carbon of
the dioxolane ring, led to macrocyclization products in all cases. The cyclohydrostannation of diacrylate
10 proceeded with complete diastereoselectivity. The cyclohydrostannation of diesters 33 and 34 with
hydrides 12 and 14 in all cases only afforded one stannylated macrocycle.
Received 18 February 2016
Accepted 25 February 2016
Available online xxxx
Ó 2016 Elsevier Ltd. All rights reserved.
1. Introduction
epimers, the corresponding unsaturated diesters 6 and 9 will also
be mixtures of the corresponding epimers.
Macrolides, i.e., macrolactones containing more than 8 mem-
bers, are found in natural products obtained from bacteria, insects,
and plants. Taking into account their biological and medicinal
activity, a number of synthetic strategies and methodologies have
been developed for macrolide synthesis.1 In many of them, the cru-
cial ring-making reactions proceed with good to excellent yields.2
However, because most of these syntheses involve many steps,
the global yields are very low.3 We have recently reported a new
method which enables the synthesis of 11-membered macrodi-
olides starting from TADDOL unsaturated diesters via a tandem
cyclohydrostannation reaction using triorganotin hydrides and
diorganotin chlorohydrides. The new macrocycles were obtained
in high overall yields and with very good diastereoselectivy.4
Herein we report the results obtained in studies carried out in
order to determine the effect on the stereoselectivity of the cyclo-
hydrostannation of TADDOL dipropenoates and di-2-methyl-
propenoates by (a) varying the substituents attached to carbon
C-2 of the dioxolane ring, and (b) replacing the TADDOL four phe-
nyl groups with four bulkier naphthyl groups.
Diols 1–3 were esterified following a modified version of Kaiser
and Woodruff’s method,6 by preparing the corresponding alkox-
ides using a freshly prepared solution of n-BuLi in dry diethyl ether
at ꢀ50 °C, followed by the addition of the unsaturated acids chlo-
rides. As shown in Scheme 1, the new unsaturated diesters were
obtained in yields similar to those obtained previously in the syn-
thesis of TADDOL unsaturated diesters.7 The physical characteris-
tics of the new unsaturated diesters including 1H and 13C NMR
spectra are reported in Section 4.
The effect of the substituents attached to C-2 of the dioxolane
ring on the stereoselectivity of the cyclohydrostannation reactions,
was studied by analysis of the products obtained in the addition of
tri-n-butyl-12, trineophyl-13, and triphenyltin 14 hydrides to the
unsaturated diesters 6–11 under free radical conditions
(Scheme 2).
The reactions were performed by adding a solution of the tri-
organotin hydride in toluene to a mixture of the unsaturated die-
ster and a catalytic amount of azobis(isobutyronitrile) (AIBN) in
the same solvent. The hydrostannations were carried out under
argon, at 75 °C, and with stirring. The reactions were followed by
IR (observing the disappearance of the Sn–H absorption) and 1H
NMR spectroscopy (observing olefin disappearance and product
formation). In all cases, the optimum times of the reactions and
hydride/olefin ratios required for a quantitative yield (with respect
to olefin) were determined.
2. Results and discussion
In order to carry out our studies, we had to synthesize a series of
unsaturated diesters. The new diesters 6–11 were obtained via
acylation of known diols 1–3, as shown in Scheme 1.5 It is impor-
tant to note that because diols 1 and 2 consist of mixtures of
As shown in Scheme 2, these radical additions could in principle
lead to products of diadicion (II) and of cyclization (III). However,
can be seen below, the hydrostannations led in all cases to the
products of cyclohydrostannation (III) exclusively.
⇑
Corresponding author. Tel.: +54 291 459 000x3548; fax: +54 291 459 5187.
E-mail address: jpodesta@uns.edu.ar (J.C. Podestá).
http://dx.doi.org/10.1016/j.tetasy.2016.02.014
0957-4166/Ó 2016 Elsevier Ltd. All rights reserved.
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2
J. Scoccia et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
centers, a maximum of two or four diastereomers, respectively, are
R1
O
Ph
Ph
expected. However, taking into account that the starting diesters
consist of mixtures of epimers, a maximum of four diastereomers
in the case of diester 6, and of eight diastereomers in the case of
7 should be expected.
Ph
Ph
Ph
Ph
Ph
3
O
O
O
O
O
O
R2
R2
Ph
4
5
R1
n-BuLi (Et2O)
OH
OH
2
+
Cl
Ph
O
1
Et2O / -50 ºC
R1
R1 = H, CH3
The 119Sn NMR spectroscopic analysis of the crude products
obtained in the additions of triorganotin hydrides 12–14 to die-
ster 6, showed that in the case of the hydrostannations with
hydride 14, the expected four 119Sn signals were present. On
the other hand, the addition of hydride 12 to ester 6 (Table 1)
led to a mixture of just three diastereomers We consider it pos-
sible that in this case there might be a superposition of signals.
Ph
O
Comp.
N°
R2
Comp.
R1
N°
Comp.
N°
Yield
%
25 [a]
R1 R2
[a]D
1
H
4
H
2
CH3
5
CH3
6
7
97
64
83
61
50
57
H
CH3
H
H
H
-100.2
-72
3
Ph
8
CH3 -19
9
CH3 CH3 -67.2
10
11
H
Ph
-5.4
-4.8
CH3 Ph
In the case of the hydrostannation of
6 with trineophyltin
hydride 13, the 119Sn NMR spectrum showed that a mixture of
only two diastereomers was formed. The formation of just two
diastereomers could be explained by taking into account that
the free radical additions of hydride 13 are slower and thus
are more stereoselective than those of organotin hydrides 12
and 14.8 As shown in Table 1, the diastereomeric excess (de)
obtained in the addition of trineophyltin hydride to diester 6
was 36%. It is noteworthy that in the mixtures obtained in the
[a]. In CHCl3; c = 0.5 g/mL
Scheme 1. Synthesis of diesters 6–11 at ꢀ50 °C.
The results obtained in the hydrostannation of diesters 6 and 7
are summarized in Table 1. Since with these substrates, the cyclo-
hydrostannation led to the creation of one or two new stereogenic
R1
O
Ph
Ph
Ph
Ph
R2
Ph
O
O
O
O
SnR3
II
SnR3
R1
O
Ph
Ph
Ph
Ph
R1
O
R2
Ph
O
O
O
O
75°C, AIBN
toluene
+
6
R3SnH
+
O
Ph
I
13
R1
O
5
O
SnR3
Ph
4
3 O
N°
R
R2
Ph
7
N° R1 R2
3a
12a
8
9
2
O
12 nBu
6
7
8
H
H
H
1
Ph 12O 10
13
14
Neoph
Ph
III
Me
11
Ph
O
H
Me
9
Me Me
Ph
Neoph = Neophyl =
Ph
CH2
10
H
11 Me Ph
Scheme 2. Free radical hydrostannation of unsaturated diesters 6–11.
Table 1
Triorganotin hydrides addition to unsaturated diesters 6 and 7
Ester N°
R3SnH R
119Sna (d, ppm)
D (%)b
Time (h)
4
Yield (%)c
50
Prod. N°
6
nBu
ꢀ9.2
ꢀ9.4
3
6
3
48
32
68
8
13
35
44
15ad
ꢀ12.2
ꢀ12.9
ꢀ41
Neophyl
Ph
4
4
60
16ab
17ad
ꢀ42
ꢀ101
ꢀ101.2
ꢀ104
ꢀ105
30d
7
n-Bu
ꢀ15
ꢀ22.9
ꢀ24.8
ꢀ24.9
21
24
28
7
24
22
3
8
5
7
2
2
2
77
81
83
18ah
19ah
20ah
ꢀ20.6
ꢀ20.8
ꢀ22
Neophyl
Ph
ꢀ44.9
ꢀ45.1
ꢀ46.4
ꢀ46.5
ꢀ110
ꢀ114
ꢀ114.3
ꢀ115
ꢀ50.0
ꢀ50.2
ꢀ52.9
ꢀ53.0
ꢀ116
3
3
18
23
22
2
4
27
12
13
21
ꢀ117
ꢀ117.1
3
a
b
c
In CDCl3; chemical shifts in ppm with respect to Me4Sn.
D = % of diastereomer in the mixture from the 119Sn NMR spectra of the crude products.
After column chromatography purification.
Most of the diastereomers could not be separated from the hexaphenyldistannane formed in the reaction.
d
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J. Scoccia et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
3
additions of organotin hydrides 12 and 14, two diastereomers
were always present in higher proportion.
formation of the mixtures of four diastereomers. In the case of the
addition of trineophyltin hydride 13, where only three diastere-
omers were detected, we considered it possible that there might
also be a superposition of 119Sn NMR signals. Here again, the mix-
tures of adducts 21ad and 23ad contained two diastereomers in
higher proportions, 91% and 76%, respectively. In the addition of
trineophyltin hydride 13, one of the three peaks shown in the
119Sn NMR spectrum has an area equivalent to 89% of the total.
This result supports our assumption that the superposition of sig-
nals might explain the lower number of diastereomers detected.
On the other hand, while the additions of hydrides 12 and 13 to
diester 9 led to mixtures of the corresponding eight diastereomers,
24ah and 25ah, the addition of triphenyltin hydride 14 afforded a
mixture of only four diastereomers. The latter might be connected
with the fact that hydride 14 would make a faster hydrogen trans-
fer to the macrocyclic radical resulting from the ring closure (rad-
ical B in Scheme 3) than hydrides 12 and 13. Again, in the mixtures
of products from the hydrostannations of unsaturated diester 9
with triorganotin hydrides 12–14, the formation of two of the four
diastereomers in a higher proportion was observed obtained: 68%,
65%, and 68% respectively. The yields were in the range 50–70%.
The results obtained in the additions of hydrides 12–14 to die-
sters 10 and 11 are summarized in Table 3. As shown in Table 3, the
hydrostannations of diester 10 with the three hydrides led to the
corresponding adducts with complete stereoselectivity. Unfortu-
nately, in the case of the addition of triphenyltin hydride 14, we
were unable to completely separate the diastereomer 29 from
the hexaphenyldistannane formed in the reaction. The additions
to unsaturated diester 11 led to mixtures of the corresponding four
diastereomers that, again, we could not separate. Macrodiolide 27
was obtained as a white solid, mp 116–118 °C (EtOH), with a speci-
The yields of the mixtures of diastereomers obtained in the
cyclohydrostannations with hydrides 12 and 13 were reasonable:
50% and 60% respectively. With triphenyltin hydride 14, we were
able to separate only 30% of the diastereomers from the crude mix-
ture of reaction, which also contained hexaphenyldistannane.
As shown in Table 1, the 119Sn NMR spectroscopic analysis of
the crude products obtained in the addition of triorganotin
hydrides 12–14 to diester 7 indicates that for the hydrostannations
with triorganotin hydrides 12 and 14, seven diastereomers were
obtained. We considered it possible that this might be due to peak
superposition. Only in the addition of trineophyltin hydride 13
were the expected eight diastereomers obtained. The reactions
were faster than the hydrostannations of unsaturated diester 6,
and the yields were higher between 77% and 83%.
The structures of the products were established by taking into
account the 1H and 13C NMR characteristics of the mixtures 15–
32. We assigned the 13C NMR chemical shifts through the analysis
of the multiplicity of the signals by means of DEPT experiments
and by taking into account the magnitude of nJ(13C,119Sn) coupling
constants.9 The use of some key signals in the 13C NMR spectra
enabled us to establish that these mixtures consisted exclusively
of the products of macrocyclization. Thus, the formation of the
cycles gives rise to the existence of two carbonyl signals (C-6 and
C-10), with one of them showing 3J(119Sn,13C) coupling constants
(C-6). Other key signals include those corresponding to the carbons
resulting from the ring closure (C-7). These signals show second
order 2J(119Sn,13C) coupling constants, and the DEPT experiments
indicate that these carbons are either tertiary, when the starting
diesters are 6, 8, and 10, or quaternary when the starting diesters
are 7, 9, and 11.
fic rotation [
a
]
D
25 = ꢀ20.8 (c 0.77, CHCl3). The compound 28 was
We next carried out the free radical hydrostannation of the
unsaturated diesters 8 and 9 with the triorganotin hydrides 12–
14. In Table 2 the results of these additions are shown. In Table 2,
the 119Sn NMR spectra of the crude products obtained in the reac-
tions of ester 8 with triorganotin hydrides 12 and 14 indicated the
obtained pure by column chromatography as a white solid, mp
133–135 °C, [
a
]
25 = ꢀ6.4 (c 0.77, CHCl3). Both compounds were
D
obtained in very good yields: 80% and 83% respectively.
The 13C NMR characteristics of compounds 27 and 28 are sum-
marized in Table 4. The spectrum of compound 27 showed a signal
Table 2
Triorganotin hydrides addition to unsaturated diesters 8 and 9
N°
R3SnH R
119Sna (d, ppm)
D (%)b
Time (h)
1
Yield (%)c
60
Prod. N°
8
n-Bu
ꢀ9.2
ꢀ9.4
3
6
43
48
7
21ad
ꢀ12.2
ꢀ13.9
ꢀ40.8
ꢀ40.9
ꢀ42.2
ꢀ100.5
ꢀ100.8
ꢀ104.8
ꢀ105.7
Neoph
Ph
4
1
30
d
22ac
23ad
4
89
11
13
36
40
9
n-Bu
Neoph
Ph
ꢀ15.7
ꢀ22.6
ꢀ22.9
ꢀ24.5
ꢀ24.7
ꢀ49.8
ꢀ50.4
ꢀ52.7
ꢀ52.9
3
4
8
8
5
4
4
2
29
36
2
16
3
70
60
50
24ah
25ah
26ad
ꢀ15.9
ꢀ20.5
ꢀ20.7
ꢀ45
32
36
14
13
1
ꢀ45.4
ꢀ46.6
ꢀ46.8
1
ꢀ116.4
ꢀ124.5
ꢀ129.1
ꢀ137.8
44
13
24
20
a
b
c
In CDCl3; chemical shifts in ppm with respect to Me4Sn.
D = % of diastereomer in the mixture from the 119Sn NMR spectra of the crude products.
After column chromatography purification.
The mixture of diastereomers could not be separated from the hexaphenyldistannane formed in the reaction.
d
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J. Scoccia et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
R1
SnR3
CH2
O
SnR3
CH2
Ph
Ph
Ph
O
Ph
O
R2
R2
R3Sn
O
H
H2C
O
I
Ph
Ph
H
O
H
O
-R3Sn
O
H
C
R1
O
Ph
Ph
O
Ph
O
Ph
R1
A
B
R3SnH
III
Scheme 3. Mechanism of the free radical cyclohydrostannation of unsaturated diesters.
Table 3
Triorganotin hydrides addition to unsaturated diesters 10 and 11
Ester N°
R3SnH R
119Sna (d, ppm)
D (%)b
Time (h)
Yield (%)c
Prod. N°
10
nBu
Neoph
Ph
ꢀ13
ꢀ42
100
100
100
1
1
2
80
83
d
27
28
29
ꢀ105
11
nBu
ꢀ16
ꢀ21
26
46
18
10
48
6
1
16
1
54
42
83
30ad
31ad
32ad
ꢀ23
ꢀ25
Neoph
Ph
ꢀ45
ꢀ47
ꢀ50
7
ꢀ53
39
23
30
44
3
ꢀ111
ꢀ115
ꢀ116
ꢀ117
a
b
c
In CDCl3; chemical shifts in ppm with respect to Me4Sn.
D = % of diastereomer in the mixture from the 119Sn NMR spectra of the crude products.
After column chromatography purification.
The mixture of diastereomers could not be separated from the hexaphenyldistannane formed in the reaction.
d
should belong to C-7. Of the two signals corresponding to the car-
bonyl groups at 170.93 ppm and 175.55 ppm, the signal at the
lower field has a third order coupling constant 3J(13C,119Sn) of
33.2 Hz, and could be ascribed to C-6. The value of 33.2 Hz for
the 3J(119Sn,C@O) coupling constant might be associated with dihe-
dral angles of 20/140° between the C@O group (C-6) and the
tributylstannyl group.9
Table 4
13C NMR characteristics of the new macrodiolides 27 and 28a
O
Ph
Ph
13
O
SnR3
5
6
4
3 O
R
N°
7
Ph
Ph
3a
12a
8
2
nBu
Neoph
27
28
1O
9
12O 10
Ph
11
Similarly, the 3J(119Sn,C-8) coupling constant of compound 27 is
25.1 Hz, a value which is compatible with the dihedral angles of
45/130° between C-8 and the tributylstannyl group.
O
Ph
Cycle N°
27b
28c
C-2
C-10
C-8 3J(Sn,C)
C-7 2J(Sn,C)
C-6 3J(Sn,C)
In the case of compound 28, the 3J(119Sn,C@O) with a value of
45.7 Hz could be associated with dihedral angles of 20/140°; the
3J(119Sn,C-8) coupling constant of 18.9 Hz suggests dihedral angles
of 60/120°. These data indicate that the structures proposed for
compounds 27 and 28 are essentially correct.
Unfortunately, we were unable to obtain crystals suitable for
crystallographic analysis. However, comparing the 13C NMR spec-
tra of 27 and 28 with the spectra of the corresponding macrodi-
olides obtained via hydrostannation of TADDOL’s diacrylate with
triorganotin hydrides 12 and 134 we can conclude that the config-
urations could be the same. It should be added that we had previ-
ously been able to establish the absolute configuration of this type
of molecules.4b
112.49
112.30
170.93
170.78
30.81 (25.1)
30.83 (18.9)
43.75 (16.7)
42.79 (13.7)
175.55 (33.2)
175.11 (45.7)
a
In CDCl3; chemical shifts, d, in ppm with respect to TMS; coupling constants, n
J
(Sn,C) in Hz (in parentheses).
b
Other signals: 9.82 (326.2); 12.52 (345.9) (C-13); 14.06; 27.52 (55.2); 29.31
(19.7); 34.93 (C-9); 79.68 and 79.76 (C-3a, C-12a); 87.44 and 87.48 (C-4, C-12);
125.34; 126.18; 126.21; 126.83; 127.00; 127.17; 127.20; 127.45; 127.51; 127.55;
128.53; 128.65; 129.33; 138.86; 139.20; 144.05; 144.08; 144.55.
c
Other signals: 15.31 (179.5) (C-13); 26.89 (C-9); 32.81; 33.13; 33.50; 34.47;
37.86; 38.09; 39.30 (340.3); 79.52 and 79.60 (C-4, C-12); 87.36 and 87.38 (C-3a, C-
12a); 125.22; 125.33; 125.49; 125.89; 125.19; 126.86; 127.00; 127.16; 127.21;
127.54; 128.06; 128.38; 128.50; 128.58; 128.30; 138.80; 139.02; 143.86; 143.90;
144.45; 144.50; 150.48 (21.2); 151.14 (18.0).
at 43.75 ppm with a 2J(13C,119Sn) coupling constant of 16.7 Hz, and
the DEPT indicates that it is a primary C atom. Therefore, this signal
The diastereoselectivity observed in the hydroestannation of
diester 10 with hydrides 12–14, could be connected with the
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J. Scoccia et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
5
In the case of unsaturated diesters 6–11, the two factors that
dominate the rate of addition to the olefins, i.e., electronic and
steric, are both favorable: the alkene substituent (the ester group)
is electron withdrawing, and the b-carbon of acrylate and
methacrylate esters 6–11 is unsubstituted and therefore there is
no steric hindrance for the addition.
O
R1
Nph
Nph
O
O
O
Nph
O
Nph
R1
O
Nph = 1-Naphthyl =
In order to determine the effect of the change of the steric vol-
ume of the diphenylmethyl moieties of TADDOL on the stereose-
lectivity of the hydrostannation of unsaturated diesters, the four
phenyl substituents were replaced by naphthyl groups (Fig. 1).
Comp.
25 [a]
R1
R2
[α]D
N°
34
35
H
CH3
H
H
-170.0
-284.2
The esterification of the known a,a, ,
a0 a0-tetranaphtyl-1,3-diox-
olan-4,5-dimethanol 3312 with acid chlorides 4 and 5 using the
protocol described above, led to the new unsaturated diesters 34
and 35 in yields of 86% and 50%, respectively (Fig. 1; TADDOL-Naph
denotes the replacement of TADDOL’s phenyl substituents by 1-
naphthyl groups).
[α]. In CHCl3; c = 0.5 g/mL.
Figure 1. New unsaturated diesters derived from TADDOL-Naph 33.
existence of attractive noncovalent interactions
(p-stacking)
The additions were carried out under the experimental condi-
tions used previously. The results obtained in the hydrostannation
of diesters 34 and 35 with triorganotin hydrides 12 and 14 are
summarized in Table 5. All attempts to add trineophyltin hydride
13 to 34 and 35 were unsuccessful: after 48 h under free radical
conditions, the starting substrates were recovered. The additions
of triphenyltin hydride 14 took place with an average yield of
77.5%, while the average yield of the hydrostannations with tri-
nbutyltin hydride 12 was 56.5%. Scheme 4 summarizes the free
radical addition of organotin hydrides 12 and 14 to diester 35.
The specific rotations of the new macrocycles included in
Table 5, are higher than those of their TADDOL analogues. Thus,
the specific rotations of the equivalent macrocyclic adducts of
compounds 36–39 obtained in the hydrostannation of TADDOL’s
diacrylates and dimetacrylates are ꢀ78, ꢀ65, ꢀ116, and ꢀ100,
respectively.
between the phenyl groups attached to C-2 of the dioxolane ring
and the gem diphenylmethyl units attached to C-4 and C-5 of die-
ster 10. These interactions could generate a more rigid structure
that would force the intermediate alkyl radical formed in the first
step of the reaction (radical A, Scheme 3) to add to the second ole-
finic group in a preferential way on one of the faces of the double
bond, giving rise to the observed selectivity.
These cyclohydrostannations can be explained by assuming
that the triorganotin radical will add to the backbone of one of
the unsaturated groups, thus leading to the alkyl radical A
(Scheme 3) which in turn adds to the less substituted carbon of
the other olefinic group leading to the product of endocyclization,
i.e., radical B. The final step is the hydrogen transfer from the
organotin hydride to the cyclic radical to give the product of cyclo-
hydrostannation III (Scheme 3).4
It is known that this tandem radical cyclization process takes
place with very high regio- and diastereoselectivity, with the endo-
cyclization mode being favored.10 Both polar and steric effects may
affect radical cyclization. Since carbon radicals are nucleophilic, the
presence of electron-withdrawing substituents activate alkenes
toward the addition by such radicals. Steric effects are also critical
in determining the ease of carbon radical addition to alkenes, i.e.,
substitution at the olefin site of radical attack usually reduces
the rate of addition.11
As shown in Table 5, the cyclohydrostannations took place with
complete diastereoselectivity. Of the two diastereomers expected
in the additions to diacrylate 34, only one was obtained. Similarly,
the hydrostannations of methacrylate 35 with hydrides 12 and 14
that should lead to four stereoisomers with the creation of two
new stereocenters, gave just one diastereomer. These results
clearly demonstrate that the replacement of TADDOL’s four phenyl
groups with four bulkier naphthyl groups results in a dramatic
increase of the stereoselectivity.
Table 5
Triorganotin hydrides addition to unsaturated diesters 33 and 34
a
25
Ester N°
R3SnH R
119Sn (d, ppm)
Time (h)
Yield (%)b
[a
]
(c, g/mL)c
Prod. N°
D
34
n-Bu
Ph
ꢀ13.6
1
1
63
78
ꢀ228.5
ꢀ105.1
36
37
ꢀ102.7
35
n-Bu
Ph
ꢀ20.3
24
24
50
77
ꢀ319.6
ꢀ136
38
39
ꢀ116.0
a
b
c
In CDCl3; ppm with respect to Me4Sn.
After column chromatography purification.
In CHCl3; c = 0.77 g/mL.
Nph
O
O
Nph
O
O
Nph
SnR3
R
Nph
O
O
75°C, AIBN
toluene
R3SnH
+
O
O
O
O
N°
Nph
Nph
Nph
N°
R
O
O
Nph
37
38
n-Bu
Ph
12 n-Bu
14
35
Ph
Scheme 4. Free radical hydrostannation of unsaturated diester 35.
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6
J. Scoccia et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
Table 6
13C NMR characteristics of the new macrodiolides 38 and 39a
Nph
O
7
13
8
Nph
3 O
2
O
5
SnR3
14
R
N°
6
4
3a
12a
12
n-Bu 37
Ph 38
9
O
1
10
O
Nph
11
O
Nph
Compd N°
C-10
C-6 3J(Sn,C)
C-7 2J(Sn,C)
C-8 3J(Sn,C)
C-14 3J(Sn,C)
38b
39c
175.76
175.32
175.94 (13.3)
176.33 (14.5)
46.97 (21.6)
68.35 (27.8)
48.84 (11.6)
46.93 (NO)
30.42 (13.7)
30.38 (15.0)
a
In CDCl3; chemical shifts, d, in ppm with respect to TMS; coupling constants, nJ(Sn,C) in Hz (in parentheses); NO = not observed.
Other signals: 10.51 (327.7); 13.88; 18.89; 21.18 (334.3); 26.15; 26.63; 27.32 (56.5); 29.23 (18.2); 30.26; 36.31; 77.83; 78.74; 87.95; 88.94; 110.44; 123.66; 123.99;
b
124.17; 124.23; 124.34; 124.40; 124.53; 124.61; 124.97; 125.25; 126.68; 127.58; 127.72; 127.94; 128.04; 128.28; 128.46; 128.81; 129.30; 129.65; 129.67; 129.73; 130.34;
130.63; 133.04; 133.54; 134.07; 134.24; 134.35; 134.38; 136.87; 136.91; 137.17; 139.22.
c
Other signals: 18.13; 23.40; 23.68 (NO); 26.12; 26.54; 36.01; 77.76; 78.66; 88.17; 89.30; 110.33; 123.70; 123.87; 124.10; 124.31; 124.35; 124.45; 124.60; 124.66;
124.99; 125.16; 126.17; 127.54; 127.75; 128.01; 128.35; 128.54; 128.80; 129.31; 129.54; 129.70; 129.75; 130.27; 130.55; 132.93; 133.27; 134.08; 134.19; 134.35; 136.37;
136.78; 136.88; 137.01; 137.09; 137.25; 139.06; 139.88.
Nph
O
OH
R1
Nph
O
Nph Nph
SnR3
R1
O
O
O
OH
OH
LiAlH4 / Et2O
R1
HO
+
33
O
R1
Nph
O
Nph
Nph
SnR3
Nph
O
Nº
R
R1
36 n-Bu
H
H
37
38
Ph
20
Nº
R
R1 Yield
(%)
[α]D
119Sn-RMN
n-Bu CH3
a
(c, g/mL)
(δ, ppm) c
39 Ph
CH3
b
b
40
41
n-Bu
H
-13
Ph
H
75
- 35.2 (0.75)
-100
42
43
n-Bu CH3
Ph CH3
56
73
+ 2.4 (0.70)
- 3.4 (0.70)
-15
-107
a In CHCl3. b Could not be obtained pure. c In
CDCl3 ; in ppm with respect to Me4Sn.
Scheme 5. Reduction of macrocycles 36–39 with LiAlH4.
We then attempted the structural elucidation of compounds 36
and 37 by means of NMR spectrometry. We found that although
the 119Sn spectra gave just one sharp signal for each compound,
we were unable to obtain well resolved 1H and 13C NMR spectra.
The reasons for the low resolution spectra could be ascribed to a
saturation of signals due to the great number of peaks especially
in the aromatic region. In addition, the observed broad bands
and low resolution might be connected with restrictions in the
molecular movements due to the bulk of the naphthyl groups. It
should be noted that we carried out a series of experiments and
varied the concentration of the solutions, the deuterated solvent
(CDCl3, DMSO-d6, acetone-d6), and the temperature (70 °C in
DMSO-d6) without obtaining good quality spectra. The 2D-spectra
and mass spectra were also of no help in these cases.
Unfortunately, we were unable to obtain crystals suitable for
crystallographic analysis of compounds 36–39. In order to estab-
lish the structure of these compounds, we carried out the reduction
of compounds 36–39 with LiAlH4 in ether. The reductions led to
mixtures of the corresponding triorganotin diols and
tetranaphthyl-1,3-dioxolan-4,5-dimethanol 33, as shown in
a,a, , -
a0 a0
Scheme 5.
The reactions were monitored by TLC and FT-IR, and stirred at rt
until the IR spectrum showed no mC@O band. The structures of com-
pounds 40–43 were confirmed by comparison with authentic sam-
ples previously obtained.4 Diol 40 could not be isolated pure from
the chromatography, but we were able to obtain mixtures enriched
in 40 that enabled us to achieve its spectroscopic characterization.
These results demonstrate that the proposed structures for the
starting macrocycles 36–39 are essentially correct.
The 1H and 13C NMR spectra of compounds 38 and 39, were
again of poor quality. However, in this case we were able to obtain
enough information for establishing the connectivity between the
carbon atoms. The 13C NMR characteristics of the new triorganotin
substituted macrodiolides 38 and 39 are included in Table 6.
The presence in 38 and 39 of two carbonyl signals, one of which
showed a 3J(119Sn,13C@O) coupling constant, indicates that these
compounds are the macrocycles product of the cyclohydrostanna-
tion of diester 34. In the DEPT experiments of compounds 37 and
38, the signals corresponding to the quaternary carbon C-7 disap-
pear, thus confirming the formation of the macrocycle.
3. Conclusions
In order to study the effect of the introduction of several sub-
stituents to TADDOL’s dipropenoates and di-2-methylpropenoates
on the stereoselectivity of the cyclohydrostannation, we have syn-
thesized and characterized eight new TADDOL unsaturated die-
sters 6–11 and 34–35.
We then studied the hydrostannation of diesters 6–11 contain-
ing different combinations of substituents at the C-2 carbon of the
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J. Scoccia et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
7
TADDOL dioxolane ring. Diesters 6 and 7 (with Ph and H sub-
4.2.1. ((4R,5R)-2-Phenyl-1,3-dioxolane-4,5-diyl)bis(diphenyl-
methylene) diacrylate 6
stituents at C-2), 8 and 9 (with Ph and Me), and 10 and 11 (with
two Ph groups at C-2) were hydrostannated with tri-nbutyl-12, tri-
neophyl-13, and triphenyltin 14 hydrides. The additions led in all
cases to products of macrocyclization. The hydrostannation of
unsaturated diesters 6–9 took place with low diastereoselectivity.
Diacrylates 6 and 8 led to four stereoisomers and the dimethacry-
lates 7 and 9 led to eight diastereomers. The latter was due to the
existence of epimers. However, in all cases two stereoisomers were
in a higher proportion. On the other hand, for the hydrostannation
of diacrylate 10, the two phenyl groups attached to carbon C-2,
with triorganotin hydrides 12–14 proceeded with complete
diastereoselectivity and in the three cases yielded only one of the
two possible diastereomers. In the case of dimethacrylate 11, the
expected formation of the four diastereomers was observed (the
creation of two new stereocenters). Here, again, two diastereomers
out of the four were formed in higher proportion.
A solution of 1 (2.0 g, 3.89 mmol) in dry Et2O (45 mL) under
argon, was cooled to ꢀ50 °C and then a solution of n-BuLi in Et2O
(5.2 mL, 9.34 mmol, 1.8 M) was added slowly with a syringe. The
mixture was kept at ꢀ50 °C for 1 h and the acryloyl chloride
(0.97 mL, 12 mmol) was added slowly. The mixture was allowed
to warm to room temperature and then stirred overnight. The reac-
tion was quenched by the addition of aqueous saturated sodium
bicarbonate solution (60 mL). The organic layer was separated
and the aqueous layer was extracted with Et2O (3 ꢁ 30 mL). The
combined organic extracts were washed once with water (20 mL)
and brine (20 mL), and then dried over anhydrous magnesium sul-
fate. The solvent was removed under reduced pressure. The white
solid obtained was structurally characterized as the desired pro-
duct 6 (2.34 g, 3.76 mmol, 97%) without the need for further purifi-
cation. Mp 129–131 °C.; [
a]
25 = ꢀ100 (c 0.5, CHCl3); 1H NMR
D
These results suggest that when the substituents are different,
the variation of the substituents attached to carbon C-2 of the diox-
olane ring does not improve the stereoselectivity of the cyclohy-
drostannations. When the substituents at C-2 are identical, e.g.,
TADDOL’s unsaturated diesters (two methyl substituents) and die-
sters 10 and 11 (two phenyl groups), a remarkable increase of the
stereoselectivity is observed.
(300 MHz, CDCl3): d = 4.48 (s, 1H), 5.57 (dd, 1H, J = 10.2, 1.3 Hz),
5.63 (dd, 1H, J = 10.2, 1.3 Hz), 5.82–5.97 (m, 1H), 6.12 (dd, 2H,
J = 3.9 Hz), 6.17 (dd, 1H, J = 1.26 Hz), 6.17–6.18 (m, 1H), 6.65–
6.68 (m, 1H), 6.97–7.40 (m, 25H). 13C NMR (75 MHz, CDCl3):
d = 78.0, 78.4, 86.7, 87.4, 103.9, 126.6, 126.8, 127.3, 127.4, 127.5,
127.6, 127.8, 127.9, 128.2, 128.5, 129.0, 129.1, 129.3, 130.3,
130.5, 130.7, 130.9, 136.6, 139.7; 141.2; 142.9; 143.4. 164.4,
In the case of the unsaturated diesters 34 (diacrylate) and 35
(dimethacrylate), derived from TADDOL-Naph 33, i.e., the diol in
which the four phenyl substituents of TADDOL are replaced by four
1-naphthyl groups, there is a dramatic increase in the stereoselec-
tivity of the cyclohydrostannation. The hydrostannations with both
tri-n-butyl- 12 and triphenyltin 14 hydrides of diesters 34 and 35
led in all cases to only one stannylated macrocycle, i.e., the reac-
tions took place with complete diastereoselectivity. These results
show the magnitude of the increase of the Ingold-Thorpe effect
when the phenyl groups are replaced by bulkier naphthyl groups.
164.6. FT-IR (KBr): m = 3052 (m), 3026 (m), 2985 (w), 2930 (m),
1726 (s), 1632 (m), 1497 (m), 1401 (m), 1171 (m), 1075 (m), 887
(m), 747 (s), 7079 (s) cmꢀ1. HRMS (ESI): calcd for C41H34O6Na:
645.2253 [M+Na]+; found: 645.2248.
4.2.2. ((4R,5R)-2-Phenyl-1,3-dioxolane-4,5-diyl)bis(diphenyl-
methylene)bis(2-methylacrylate) 7
The title compound was prepared from 1 to give a white solid
(1.59 g, 2.46 mmol, 64% yield). Mp 135–137 °C. SiO2 (hexane/
Et2O = 97:3); [
a
]
25 = ꢀ72 (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3):
D
d = 1.70 (s, 3H), 1.74 (s, 3H), 4.55 (s, 1H), 5.41–5.44 (m, 2H), 6.18
(dd, 2H, J = 4.8 Hz), 6.40 (dd, 2H, J = 7.6 Hz), 7.02–7.37 (m, 25H).
13C NMR (75 MHz, CDCl3): d = 18.2, 77.6, 77.1, 86.9, 87.6, 103.8,
126.8, 127.3, 127.5, 127.7, 127.8, 128.1, 128.3, 128.7, 129.1,
129.2, 129.4, 137.3, 137.4, 127.2, 136,5, 140.4, 141.6, 143.1,
4. Experimental
4.1. General
143.7, 165.8, 166.1. FT-IR (KBr):
m = 3023 (m), 2980 (w), 2926
All reactions were carried out under an argon atmosphere. Sol-
vents were dried and distilled in accordance with standard proce-
dure. Reactions were monitored by thin-layer chromatography on
silica gel plates (60F-254) visualized under UV light and/or using
5% phosphomolybdic acid in ethanol. Column chromatography
was performed over silica gel 60 (70–230 mesh). NMR spectra
were recorded at 25 °C on a Bruker Avance 300 multinuclear
instrument, using CDCl3 as solvent; chemical shifts (d) are reported
in ppm with respect to TMS, 1H and 13C. IR spectra were recorded
on a FT-IR Nicolet Nexus 470/670/870 spectrophotometer. Mass
spectra were obtained on Finnigan MAT Incos 50 Galaxy System
(DIP-MS) (EI) or Finnigan MAT 900 (ESI) spectrometers, high reso-
lution mass spectra on a Finnigan HSQ-30 (HR-EIMS) or on a Finni-
gan MAT 900 (HR-ESI-MS). The method of ionization is given in
(m), 1723 (s), 1629 (m), 1490 (m), 1401 (m), 1165 (m), 1075 (m),
884 (m), 751 (s), 705 (s) cmꢀ1. HRMS (ESI): calcd for C43H38O6Na:
673.2566 [M+Na]+; found: 673.2561.
4.2.3. ((4R,5R)-2-Methyl-2-phenyl-1,3-dioxolane-4,5-diyl)bis
(diphenylmethylene)diacrylate 8
The title compound was prepared from 2 to give a white solid
(2.0 g, 3.10 mmol, 83% yield) without the need of further purifica-
tion. Mp 138–140 °C; [
a
]
25 = ꢀ19 (c 0.5, CHCl3); 1H NMR (300 MHz,
D
CDCl3): d = 1.95 (d, 3H), 3.99–4.01 (m, 2H), 5.38–5.42 (m, 2H),
5.91–6.28 (m, 4H), 6.65–7.43 (m, 18H). 13C NMR (75 MHz, CDCl3):
d = 28.8, 79.3, 79.7, 87.3, 87.41, 109.9, 124.6; 126.3; 126.4; 126.9,
127.0, 127.2, 127.3, 127.4, 127.6, 127.7, 128.8, 129.1, 129.2,
130.0, 130.6, 130.9, 131.0, 131.1, 164.3, 164.5. FT-IR (KBr):
parentheses. Specific rotations were measured with a Polar L-lP,
m
= 3021 (m), 2982 (w), 2923 (m), 1728 (s), 1627 (m), 1492 (m),
1400 (m), 1164 (m), 1071 (m), 882 (m), 750 (s), 707 (s) cmꢀ1
.
IBZ Messtechnik instrument. The melting points were determined
with a Kofler hot stage apparatus and are not corrected. All the sol-
vents and reagents were commercially available and analytical
grade. The diols 1, 2, 3, and 33 were prepared by know
procedures.5,12
HRMS (ESI): calcd for C42H36O6Na: 659.2410 [M+Na]+; found:
659.2414.
4.2.4. ((4R,5R)-2-Methyl-2-phenyl-1,3-dioxolane-4,5-diyl)bis
(diphenylmethylene)bis(2-methyl-acrylate) 9
4.2. Synthesis of unsaturated diesters via esterification of diols
1, 2, 3, and 33 with a,b-unsaturated acid chlorides
The title compound was prepared from 2 to give a white solid
(1.50 g, 2.30 mmol, 61% yield). Mp 156–158 °C. SiO2 (hexane/
Et2O = 95:5); [
a
]
25 = ꢀ67 (c 0.5, CHCl3); 1H NMR (300 MHz, CDCl3):
D
The same procedure was used in all of the reactions. One exper-
iment is described in detail to illustrate the methods used.
d = 0.81 (s, 3H), 1.67–1.69 (m, 6H), 5.77 (dd, 4H, J = 10.3 Hz), 5.92
(dd, 2H, J = 6.0 Hz), 6.73–7.40 (m, 25H). 13C NMR (75 MHz, CDCl3):
Please cite this article in press as: Scoccia, J.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.02.014

8
J. Scoccia et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
d = 18.3, 18.4, 78.6, 79.1, 87.8, 87.9, 110.8, 124.6, 126.2, 126.9,
4.3. Addition of triorganotin hydrides to unsaturated diesters
127.0, 127.1, 127.5, 127.6, 127.7, 128.7, 129.1, 137.9 138.0, 139.5,
141.1, 143.6, 144.1, 166.1, 166.4. FT-IR (KBr):
(w), 2925 (m), 1730 (s), 1630 (m), 1495 (m), 1401 (m), 1160 (m),
1073 (m), 881 (m), 748 (s), 705 (s) cmꢀ1. HRMS (ESI): calcd for C44
40O6Na: 664.2825 [M+Na]+; found: 664.2820.
m
= 3020 (m), 2990
The same procedure was used in all of the reactions. One exper-
iment is described in detail to illustrate the methods used.
-
H
4.3.1. (3aR,7R,12aR)-2,2,4,4,12,12-Hexaphenyl-7-((tributylstan-
nyl)methyl)hexahydro-6H-[1,3]dioxolo[4,5-c][1,6]dioxacycloun-
decine-6,10(7H)dione 27
4.2.5. ((4R,5R)-2,2-Diphenyl-1,3-dioxolane-4,5-diyl)bis(diphenyl-
methylene)diacrylate 10
Diester 10 (0.12 g, 0.17 mmol) in dry toluene (5 mL) was treated
with tributyltin hydride (0.11 g, 0.34 mmol), using AIBN as a radi-
cal initiator (0.049 g, 0.3 mmol), under an argon atmosphere at
75 °C for 1 h (optimal time of reaction and adequate excess of
organotin hydride were determined in previous runs both by mon-
itoring the reaction by taking samples at intervals and observing
the disappearance of the Sn–H absorption and by IR and also by
checking that the 1H NMR spectrum of the reaction mixture did
not show the presence of unreacted olefin). The solvent was then
distilled off under reduced pressure, and the 119Sn NMR spectrum
of the crude product showed that it consisted of only one com-
pound 27. The crude product thus obtained was purified by recrys-
tallization from ethanol (0.14 g, 0.14 mmol, 80%) as a white solid,
The title compound was prepared from 3 to give a white solid
(0.88 g, 1.30 mmol, 50% yield) without the need of further purifica-
tion. Mp 180–182 °C;
[
a
]
25 = ꢀ5.4 (c 0.5, CHCl3); 1H NMR
D
(300 MHz, CDCl3): d = 5.80–5.85 (m, 4H), 6.13–6.24 (m, 2H), 6.42
(dd, 2H, J = 1.2, 17.1), 6.92–7.60 (m, 30H). 13C NMR (75 MHz,
CDCl3): d = 81.3, 87.4, 111.0, 125.42, 126.4, 127.1, 127.2, 127.4,
127.5, 127.7, 128.9, 129.1, 130.5, 131.1, 138.0, 143.0, 143.7,
164.4. FT-IR (KBr):
m = 3025 (m), 2981 (w), 2924 (m), 1721 (s),
1630 (m), 1492 (m), 1403 (m), 1162 (m), 1076 (m), 882 (m), 749
(s), 704 (s) cmꢀ1. HRMS (ESI): calcd for C47H38O6Na: 721.2566 [M
+Na]+; found: 721.2561.
4.2.6. ((4R,5R)-2,2-Diphenyl-1,3-dioxolane-4,5-diyl)bis(diphenyl-
methylene)bis(2-methylacrylate) 11
mp 115–117 °C. [
CDCl3): d = 0.63 (t, 4H, JH,H: 7.6 Hz); 0.81 (t, 9H, JH,H: 6.9 Hz);
a
]
25 = ꢀ20.8 (c 0.77, CHCl3); 1H NMR (300 MHz,
D
3
3
The title compound was prepared from 3 to give a white solid
(0.70 g, 0.97 mmol, 57% yield) without the need of further purifica-
1.16–1.57 (m, 17H); 1.93–2.27 (m, 3H); 2.47–2.61 (m, 2H); 5.94
3
3
(d, 1H, JH,H: 7.1 Hz); 6.00 (d, 1H, JH,H: 7.1 Hz); 6.63–7.44 (m,
30H). FT-IR (KBr): = 3040 (m); 3011 (m); 2946 (w); 2910 (w);
tion. Mp 203–205 °C;
[
a]
25 = ꢀ4.8 (c 0.5, CHCl3); 1H NMR
m
D
(300 MHz, CDCl3): d = 1.80 (s, 6H); 5.56 (s, 2H); 6.19 (s, 2H); 6.27
(s, 2H); 6.93–7.56 (m, 30H). 13C NMR (75 MHz, CDCl3): d = 18.3,
80.4, 87.9, 112.1, 125.2 126.3, 126.8, 126.9, 127.4, 127.6, 128.9,
1743 (s); 1600 (m); 1485 (m); 1452 (m); 1240 (m); 1160 (m);
850 (m); 750 (s); 695 (s) cmꢀ1. HRMS (ESI): calcd for C59H66O6-
SnNa: 1013.3787 [M+Na]+; found: 1013.3782.
137.9, 139.3, 143.9, 144.3, 166.2. FT-IR (KBr):
(w), 2924 (m), 1729 (s), 1628 (m), 1491 (m), 1402 (m), 1165 (m),
1073 (m), 880 (m), 750 (s), 703 (s) cmꢀ1. HRMS (ESI): calcd for C49
42O6Na: 726.2981 [M+Na]+; found: 726.2985.
m = 3022 (m), 2981
4.3.2. (3aR,7R,12aR)-2,2,4,4,12,12-Hexaphenyl-7-((tris(2-methyl-
2-phenylpropyl)stannyl)methyl)hexahydro-6H-[1,3]dioxolo[4,5-c]
[1,6]dioxacycloundecine-6,10(7H)-dione 28
-
H
The title compound was prepared from 10 to give a white solid
(0.14 g, 0.12 mmol, 83% yield). Mp 130–132 °C; SiO2 (hexane/
4.2.7. ((4R,5R)-2,2-Dimethyl-1,3-dioxolane-4,5-diyl)bis(di(naph-
thalen-1-yl)-methylene)diacrylate 34
Et2O = 90:10); [
a
]
25 = ꢀ6.4 (c 0.77, CHCl3); 1H NMR (300 MHz,
D
2
The title compound was prepared from 33 to give a pale yellow
solid (1.0 g, 1.30 mmol, 86% yield) without the need of further
CDCl3): d = 0.79 (s, 6H, JSn,H: 49.2 Hz); 1.07 (s, 9H); 1.13 (s, 9H);
1.65–1.68 (m, 2H); 2.01–2.15 (m, 4H); 2.22–2.30 (m, 1H); 5.92
3
3
purification. Mp 145–147 °C; [
a]
25 = ꢀ170 (c 0.5, CHCl3); 1H NMR
(d, 1H, JH,H: 7.3 Hz); 5.98 (d, 1H, JH,H: 7.3 Hz); 6.80–7.21 (m,
45H). FT-IR (KBr): = 3042 (m); 3011 (m); 2940 (w); 2915 (w);
D
(300 MHz, CDCl3): d = 1.47 (s, 6H); 5.46–5.53 (m, 1H); 5.97–5.95
(m, 3H); 6.39–6.43 (m, 1H); 6.55–6.64 (m, 2H); 6.91–7.02 (m,
4H); 7.12–7.16 (m, 2H); 7.30–7.84 (m, 20H); 7.91–7.94 (m, 1H);
8.22–8.25 (m, 2H). 13C NMR (75 MHz, CDCl3): d = 15.2, 79.2, 88.1,
110.9, 123.9, 124.3, 124.4, 124.7, 124.9, 125.2, 125.8, 127.7,
127.8, 127.9, 128.0, 128.6, 128.8, 129.6, 129.7, 130.4, 130.6,
130.8, 131.6, 133.2, 134.1, 134.3, 137.3, 137.9, 164.64. FT-IR
m
1741 (s); 1602 (m); 1480 (m); 1450 (m); 1242 (m); 1160 (m);
850 (m); 750 (s); 695 (s) cmꢀ1. HRMS (ESI): calcd for C77H78O6-
SnNa: 1241.4720 [M+Na]+; found: 1241.4725.
4.3.3. (3aR,7(R or S),9(R or S),12aR)-2,2,7,9-Tetramethyl-4,4,12,
12-tetra(naphthalen-1-yl)-7-((tributylstannyl)methyl)hexahydro-
6H-[1,3]dioxolo[4,5-c][1,6]dioxacycloundecine-6,10(7H)-dione
(38)
(KBr):
m = 3022 (m), 3015 (m), 2981 (w), 1731 (s), 1605 (m),
1494 (m), 1401 (m), 1163 (m), 1075 (m), 882 (m), 751 (s), 702
(s) cmꢀ1. HRMS (ESI): calcd for C53H42O6Na: 797.2291 [M+Na]+;
found: 797.2295.
The title compound was prepared from 35 to give a white solid
(0.11 g, 0.10 mmol, 54% yield). Mp 123–125 °C; SiO2 (hexane/
Et2O = 90:10); [
a
]
25 = ꢀ319 (c 0.77, CHCl3); 1H NMR (300 MHz,
D
4.2.8. ((4R,5R)-2,2-Dimethyl-1,3-dioxolane-4,5-diyl)bis(di(naph-
thalen-1-yl)-methylene)bis(2-methylacrylate) 35
CDCl3): d = 0.05 (s, 3H); 0.12 (s, 2H); 0.46–0.53 (m, 8H); 0.65 (s,
3H); 0.94 (t, 9H); 1.29–1.37 (m, 12 H); 1.47 (s, 3H); 1.56–1.67
(m, 2H); 2.55–2.67 (m, 1H); 2.77–2.88 (m, 1H); 6.38 (d, 1H);
The title compound was prepared from 33 to give a white solid
(1.2 g, 1.50 mmol, 50% yield). Mp 158–160 °C; SiO2 (hexane/
6.59–8.63 (m, 30H). FT-IR (KBr):
m = 3035 (m); 3010 (m); 2935
EtOAc = 96:4); [
a]
25 = ꢀ284 (c 0.5, CHCl3); 1H NMR (300 MHz,
(w); 2910 (w); 1743 (s); 1601 (m); 1480 (m); 1445 (m); 1242
(m); 1160 (m); 848 (m); 749 (s); 700 (s) cmꢀ1. HRMS (ESI): calcd
for C67H74O6SnNa: 1117.4407 [M+Na]+; found: 1117.4412.
D
CDCl3): d = 1.76 (s, 3H); 1.79 (s, 3H); 1.94 (s, 6H); 5.50–5.58 (m,
2H); 6.31–6.41 (m, 2H); 6.81–7.08 (m, 4H); 7.16–8.22 (m, 20H);
8.28–8.97 (m, 6H). 13C NMR (75 MHz, CDCl3): d = 18.4, 25.2, 79.3,
88.1, 111.2, 124.0, 124.3, 124.4, 124.5, 124.7, 125.2, 126.1, 126.8,
127.4, 127.7, 127.9, 128.0, 128.5, 128.9, 129.0, 129.3, 128.5,
129.7, 130.6, 133.4 134.2, 134.4, 136.3, 137.8, 138.1, 165.8. FT-IR
4.3.4. (3aR,7(R or S),9(R or S),12aR)-2,2,7,9-Tetramethyl-4,4,12,
12-tetra(naphthalen-1-yl)-7-((triphenylstannyl)methyl)hexahydro-
6H-[1,3]dioxolo[4,5-c][1,6]dioxacycloundecine-6,10(7H)-dione
39
(KBr):
m = 3025 (m), 3019 (m), 2986 (w), 1728 (s), 1603 (m),
1490 (m), 1405 (m), 1161 (m), 1073 (m), 881 (m), 752 (s), 700
(s) cmꢀ1. HRMS (ESI): calcd for C55H46O6Na: 825.3192 [M+Na]+;
found: 825.3187.
The title compound was prepared from 35 to give a white solid
(0.17 g, 0.15 mmol, 77% yield). Mp 127–129 °C; SiO2 (hexane/
Et2O = 90:10); [
a
]
D
25 = ꢀ136 (c 0.77, CHCl3); 1H NMR (300 MHz,
Please cite this article in press as: Scoccia, J.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.02.014

J. Scoccia et al. / Tetrahedron: Asymmetry xxx (2016) xxx–xxx
9
4. (a) Gerbino, D. C.; Koll, L. C.; Mandolesi, S. D.; Podestá, J. C. Organometallics
2008, 27, 660–665; (b) Gerbino, D. C.; Scoccia, J.; Koll, L. C.; Mandolesi, S. D.;
Podestá, J. C. Organometallics 2012, 31, 662–671.
CDCl3): d = ꢀ0.23 (s, 3H); ꢀ0.10 (s, 3H); 0.19 (d, 3H); 0.63 (s, 3H);
1.28–1.31 (m, 1H); 1.56–1.60 (m, 1H); 2.18 (d, 1H); 2.40–2.49 (m,
3
1H); 2.67–2.73 (m, 1H); 6.24 (d, 1H, JH,H: 6.1 Hz); 6.54 (d, 1H, 3JH,
5. (a) Seebach, D.; Beck, A. K.; Imwinketried, R.; Roggo, S.; Wonnacott, A. Helv.
Chim. Acta 1987, 70, 954–974; (b) Ito, Y. N.; Ariza, X.; Beck, A. K.; Bohác, A.;
Ganter, C.; Gawley, R. E.; Kühnle, F. N. M.; Tuleja, J.; Wang, Y. M.; Seebach, D.
Helv. Chim. Acta 1994, 77, 2071–2110; (c) Narasaka, N.; Iwasawa, N.; Inoue, M.;
Yamada, T.; Nakashima, M.; Sujimori, J. J. Am. Chem. Soc. 1989, 111, 5340–5345;
(d) Weber, E.; Dörpinghaus, N.; Goldberg, I. J. J. Chem. Soc., Chem. Commun.
1988, 23, 1566–1568; (e) Irurre, J.; Alonso-Alija, C.; Piniella, J. F.; Alvarez-
Larena, A. Tetrahedron: Asymmetry 1992, 3, 1591–1596.
H: 6.1 Hz); 1.48–6.62 (m, 4H); 7.79–7.88 (m, 43H). FT-IR (KBr):
m
= 3038 (m); 3015 (m); 2941 (w); 2912 (w); 1740 (s); 1600 (m);
1480 (m); 1450 (m); 1240 (m); 1161 (m); 850 (m); 751 (s); 699
(s) cmꢀ1
. HRMS (ESI): calcd for C73H62O6SnNa: 1154.3568
[M+Na]+; found: 1154.3572.
6. Kaiser, E. M.; Woodruff, R. A. J. Org. Chem. 1970, 35, 1198–1199.
7. Scoccia, J.; Gerbino, D. C.; Terraza, V. F.; Zúñiga, A. E.; Podestá, J. C. Eur. J. Org.
Chem. 2013, 20, 4418–4426.
Acknowledgments
8. (a) Dodero, V. I.; Koll, L. C.; Faraoni, M.; Mitchell, T. N.; Podestá, J. C. J. Org. Chem.
2003, 68, 10087–10091; (b) Faraoni, M. B.; Dodero, V. I.; Koll, L. C.; Zúñiga, A. E.;
Mitchell, T. N.; Podestá, J. C. J. Organomet. Chem. 2006, 691, 1085–1091.
9. (a) Doddrell, D.; Burfitt, I.; Kitching, W.; Lee, C.-H.; Mynott, R. J.; Considine, J. C.;
Kuivila, H. G.; Sarma, R. H. J. Am. Chem. Soc. 1974, 96, 1640–1642; (b) Mitchell,
T. N.; Podestá, J. C.; Ayala, A. D.; Chopa, A. B. Mag. Reson. Chem. 1988, 26, 497–
500.
This work was supported by grants from ANPCyT (Capital Fed-
eral, Argentina/BID, PICT project N° 2644), CONICET (Buenos Aires,
Argentina, PIP project N° 112-201101-00828), and Universidad
Nacional del Sur (Bahía Blanca, Argentina, PGI 24/Q041). A fellow-
ship from CONICET to J.S. is acknowledged.
10. (a) Porter, N. A.; Chang, V. H.-T. J. Am. Chem. Soc. 1987, 109, 4976–4981; (b)
Porter, N. A.; Chang, V. H.-T.; Magnin, D. R.; Wright, B. T. J. Am. Chem. Soc. 1988,
110, 3554–3560; (c) Porter, N. A.; Lacher, B.; Chang, V. H.-T.; Magnin, D. R. J.
Am. Chem. Soc. 1989, 111, 8309–8310.
11. (a) Walling, C. Tetrahedron 1985, 41, 3887–3900; (b) Giese, B. Angew. Chem., Int.
Ed. Engl. 1983, 22, 753–764.
References
1. Macrolides Antibiotics: Chemistry Biochemistry and Practice; Omura, S., Ed., 2nd
ed.; Academic Press, 2002.
2. Nakata, T. Chapter 4 in Ref. 5.
12. Beck, A. K.; Bastani, B.; Plattner, D. A.; Petter, W.; Seebach, D.; Braunschweiger,
H.; Gysi, P.; La Vecchia, L. Chimia 1991, 45, 238–244.
3. Shindo, M. Top. Heterocycl. Chem. 2006, 5, 179–254. and references therein
cited.
Please cite this article in press as: Scoccia, J.; et al. Tetrahedron: Asymmetry (2016), http://dx.doi.org/10.1016/j.tetasy.2016.02.014