A highly atom efficient, solvent promoted addition of tetraallylic, tetraallenic, and tetrapropargylic stannanes to carbonyl compounds

Article abstract of DOI:10.1021/jo015904x

Tetraallylic, tetraallenic, and tetrapropargylic stannanes (0.25 equiv) react with aldehydes in methanol to provide unsaturated alcohols in good to excellent yields (56-99%). These reactions proceed exclusively with allylic rearrangement for tetra(2-butenyl)tin 2b and tetra(1,2-butadienyl)-tin 16c and predominantly with allylic rearrangement for tetrapropadienyltin 16a and tetra(2-butynyl)tin 6e. Allylation reactions also proceeded smoothly with reactive ketones such as ethyl pyruvate (9a) and cyclohexanone (9b). The corresponding TFA-catalyzed reactions of dimethyl acetals 4d and 4e are regiospecific with allylic rearrangement.

Full text of DOI:10.1021/jo015904x

J . Org. Chem. 2001, 66, 7811-7817
7811
A High ly Atom Efficien t, Solven t P r om oted Ad d ition of
Tetr a a llylic, Tetr a a llen ic, a n d Tetr a p r op a r gylic Sta n n a n es to
Ca r bon yl Com p ou n d s
Adam McCluskey,*,† I. Wayan Muderawan,‡ Muntari,‡ and David J . Young*,‡
Chemistry, School of Biological and Chemical Sciences, The University of Newcastle, University Drive,
Callaghan, NSW 2308, Australia, and Faculty of Science and Technology, Griffith University,
Nathan Campus, Brisbane, Qld 4111, Australia
amcclusk@mail.newcastle.edu.au
Received J uly 10, 2001
Tetraallylic, tetraallenic, and tetrapropargylic stannanes (0.25 equiv) react with aldehydes in
methanol to provide unsaturated alcohols in good to excellent yields (56-99%). These reactions
proceed exclusively with allylic rearrangement for tetra(2-butenyl)tin 2b and tetra(1,2-butadienyl)-
tin 16c and predominantly with allylic rearrangement for tetrapropadienyltin 16a and tetra(2-
butynyl)tin 6e. Allylation reactions also proceeded smoothly with reactive ketones such as ethyl
pyruvate (9a ) and cyclohexanone (9b ). The corresponding TFA-catalyzed reactions of dimethyl
acetals 4d and 4e are regiospecific with allylic rearrangement.
In tr od u ction
In this procedure the carbonyl compound and stannane
(0.25 equiv) react rapidly in methanol, water,7 or ionic
liquid8 over a range of temperatures from room temper-
ature (aldehydes) to 100 °C (ketones over approximately
4-20 h; Weinreb amides over 5 days). The resulting
homoallyl alcohol can be easily separated from insoluble
tin methoxide salts. (Weinreb amides afford moderate to
good yields of the corresponding allylic ketones.) Unlike
the corresponding reactions of allyltrialkylstannanes, this
procedure does not require anhydrous conditions, the use
of expensive catalysts, or chromatography to remove the
organotin byproduct. Acetals are also allylated with this
reagent, but require the addition of TFA or silica gel.9
This latter procedure is particularly suited to the reaction
of unstable amino aldehydes, which are more conve-
niently handled as the corresponding acetals.
It has long been known that the allylation of carbonyl
groups provides homoallylic alcohols possessing useful
functionality suitable for further elaboration.1 Not sur-
prisingly, numerous protocols have been developed al-
lowing this transformation to be achieved with high levels
of regio- and stereocontrol.2 A large body of work revolves
around the use of allylstananne reagents to act as allyl
donors and their use in the synthesis of complex natural
products.3 Although these reactions are typically regio-
selective and high yielding, environmental concerns
regarding disposal and poor atom efficiency abound. One
of the great remaining difficulties associated with the use
of allylstannane reagents, which has not been adequately
addressed, is the removal of the stannane byproducts.4
Recently, we and others reported a particularly mild,
convenient, environmentally friendly procedure for the
chemoselective allylation of aldehydes5 and Weinreb
amides6 with commercially available tetraallylstannane.
The related propargylation and allenylation of alde-
hydes has also received considerable attention over the
past decade. We10 and others and have developed a
variety of methods to achieve regio- and stereocontrol
which have been employed for the asymmetric synthesis
of complex natural products.11
† The University of Newcastle.
‡ Griffith University.
(1) For reviews see: (a) Yamamoto, Y.; Asao, N. Chem. Rev. 1993,
93, 2207. (b) Marshall, J . A. Chem. Rev. 1996, 96, 31. (c) Thomas, E.
J . Chem. Commun. 1997, 411.
(2) See for example: (a) Marshall, J . A. J . Org. Chem. 1996, 61,
4247. (b) Hamasaki, R.; Chounan, Y.; Horino, H.; Yamamoto, Y.
Tetrahedron Lett. 2000, 41, 9883. (c) Marshall, R. L.; Muderawan, I.;
Wayan; Young, D. J . J . Chem. Soc., Perkin Trans. 2 2000, 957. (d)
Taylor, N. H.; Thomas, E. J . Tetrahedron 1999, 55, 8757. (e) Keck, G.
E.; Yu, T. Org. Lett. 1999, 1, 289. (f) Curran, D. P.; Luo, Z. Med. Chem.
Res. 1998, 8, 261.
(3) (a) Micalizio, G. C.; Pinchuk, A. N.; Roush, W. R. J . Org. Chem.
2000, 65, 8730. (b) Micalizio, G. C.; Roush, W. R. Tetrahedron Lett.
1999, 40, 3351. (c) Williams, D. R.; Clark, M. P.; Berliner, M. A.
Tetrahedron Lett. 1999, 40, 2287. (d) Arista, L.; Gruttadauria, M.;
Thomas, E. J . Synlett 1997, 627.
(4) Enholm, E. J .; Gallagher, M. E.; Moran, K. M.; Lombardi, J . S.;
Schulte, J . P., II. Org. Lett. 1999, 1, 689.
(5) (a) Cokely, T, M.; Marshall, R. L.; McCluskey, A.; Young, D. Y.
Tetrahedron Lett. 1996, 37, 1905. (b) Cokely, T, M.; Harvey, P. J .;
Marshall, R. L.; McCluskey, A.; Young, D. J . J . Org. Chem. 1997, 62,
1961. (c) Casolari, S.; D’Addrio, D.; Tagliavini, E. Org. Lett. 1999, 1,
1061.
(6) McCluskey, A.; Garner, J .; Caballero, S.; Young, D. J . Tetrahe-
dron Lett. 2000, 41, 8147.
We have previously suggested that the methanol-
promoted allylation of carbonyl compounds might be
concerted with the activating influence of the solvent
primarily as a result of hydrogen bonding to the carbonyl
oxygen.5d (The reaction in ionic liquids is believed, in part,
to be due to the encapsulation of small quantities of water
in the “dry” liquid and the serendipitous entrainment of
water within the extracting solvent (diethyl ether).12)
Thus, the allylation should be regiospecific with addition
(7) McCluskey, A. Green Chem. 1999, 1, 161.
(8) Gordon, C. M.; McCluskey, A. Chem. Commun. 1999, 1431.
(9) McCluskey, A.; Mayer, D. M.; Young, D. J . Tetrahedron Lett.
1997, 38, 5217.
(10) McCluskey, A.; Muderawan, I. W.; Muntari; Young, D. J . Synlett
1998, 909.
(11) (a) Marshall, J . A.; Lu, Z. H.; J ohns, B. A. J . Org. Chem. 1997,
62, 837. (b) Marshall, J . A.; Hinkle, K. W. J . Org. Chem. 1997, 62,
5989.
(12) Gordon, C. M.; McCluskey, A. Manuscript in preparation.
10.1021/jo015904x CCC: $20.00 © 2001 American Chemical Society
Published on Web 10/12/2001

7812 J . Org. Chem., Vol. 66, No. 23, 2001
McCluskey et al.
5, with 2b a mixture of 6 and 7, and with 2c only 8 were
expected as the products of these reactions (Scheme 2).
As can be seen from Table 2, aldehyde addition to
stannane 2a proceeded cleanly, under all of the conditions
examined, and in high yield (ca. 90%) affording the
expected â-methyl homoallylic alcohols 5a -f (Table 2,
entries 1-6) as the sole product of the reaction. The
corresponding reaction with stannane 2b was regiospe-
cific proceeding with allylic rearrangement, but with low
diastereoselectivity in favor of the syn isomers 6a -f over
the anti isomers 7a -f (de ) 0-30%). As with stannane
2a , the yields of homoallylic alcohols from 2b were
excellent (Table 2, 65-80%, entries 9-26). Finally in this
series, tetraalylic stannane 2c also afforded good to
excellent yields of the â-methyl homoallylic alcohols 8a -f
(Table 2, 57-82%, entries 29-34). In all instances, the
product could be isolated by aqueous workup or by
evaporation of the solvent and washing the resulting
slurry of allylated product 5-8 and stannane salts with
dichloromethane followed by Kugelrohr distillation or
filtration through silica gel. This procedure is markedly
simpler than those associated with allyltrialkylstan-
nanes.
F igu r e 1. 119Sn {1H} NMR spectrum of 2b in CDCl3. Assign-
ments (from L to R): cis,cis,cis,cis (δ -27.53, 7.2%); cis,cis,-
cis,trans (δ -31.73, 26.6%); cis,cis,trans,trans (δ -36.18,
37.2%); cis,trans,trans,trans (23.9%); trans,trans,trans,trans
(δ -45.92, 5.1%).15
Sch em e 1
Several of the allylation experiments with stannane
2b and aldehydes 3 were conducted both at room tem-
perature in methanol and at methanol reflux. Compari-
son of the outcomes of these reactions indicates that there
is no significant change in the final reaction yield;
however, elevated temperature shows a slight syn isomer
6 preference with aromatic aldehydes 3d -f. For example,
the room-temperature reaction with 3d affords 6d + 7d
as a 50:50 mixture (Table 2, entry 16, 83%); at methanol
reflux 55:45 (Table 2, entry 17, 80%); with 3e at room-
temperature yielding 6e + 7e as a 56:44 mixture (Table
2, entry 20, 71%); and at methanol reflux 59:41 (Table
2, entry 21, 71%).
of the aldehyde or ketone to the γ-position of the allylic
triad. As part of an ongoing investigation into the
regiochemistry of this reaction, we have extended it to
the analogous propargylation and allenylation reactions.
In previous studies from our laboratories, we have
noted a significant acceleration in reaction rate after
transfer of the first allyl group from tetraallylstannane
to the carbonyl compound.5d We postulated that this
acceleration was due, at least in part, to the in situ
generation of triallylmethoxystannane, which acted as
a Lewis acid catalyst the addition of the remaining allyl
groups. We envisaged that the addition of a methoxy-
stannane Lewis acid, would yield ostensibly the same
outcome in these reactions by mimicking the in situ
generated Lewis acid, further strengthening our initial
hypothesis. Accordingly, we examined the effect of con-
ducting allylation reactions in the presence of dimeth-
yldimethoxystannane (DDS, 10 mol %).
Resu lts a n d Discu ssion
Syn th esis of Tetr a a llylic Sta n n a n es 2a -c. Using
a slight modification of the literature procedure, that is
allowing the magnesium metal to stir at room tempera-
ture overnight under an nitrogen atmosphere (formation
of a “magnesium mirror”), Grignard methodology (Scheme
1) and the readily available allylic chlorides 1 rapidly
afforded the methyl-substituted teraallylic stannanes
2a -c in excellent yield.13
Chloride 1b (E/Z ) 90:10) yielded a mixture of tetra-
organostannanes that isomerized to an almost perfect
binomial distribution of the five diastereomers of 2b on
standing (Figure 1). Stereochemical assignments were
based on comparisons with the corresponding 13C and
119Sn NMR data for 2-butenyltributylstannane.14
Rea ction s of Tetr a a llylic Sta n n a n es (2a -c) w ith
Ald eh yd es a n d Aceta ls. The addition of allylic stan-
nanes 2a -c to aldehydes 3a -f was examined under a
variety of reaction conditions, including stirring in metha-
nol at room temperature (30 °C), methanol reflux,
methanol reflux in the presence of dimethyldimethoxy-
stannane (DDS) and in acidic (HCl) THF. With 2a only
Interestingly, DDS acted in an almost identical fashion
to HCl (in THF) allowing a slight increase in reaction
yield and a change in the ratio of products. For example,
the reaction of stannane 2b and aldehyde 3d in methanol
with added DDS (Table 2 entry 18) affords 6d + 7d as a
60:40 mixture (Table 2, entry 18, 92%). The correspond-
ing reaction in HCl/THF affords identical products as a
62:38 mixture (Table 2, entry 19, 88%). Indeed, in our
hands, the HCl/THF-mediated reactions proceeded in a
fashion analogous to those conducted with added DDS,
that is, an average of a 10% increase in product yield
and a concurrent slight increase in syn (6) selectivity (de
) 0-33%). However, we note that this HCl/THF meth-
odology is not suited to reactions involving acid-sensitive
groups.
(13) (a) Gampe, D.; J acob, K.; Theile, K. H. Z. Chem. 1984, 25, 151.
(b) Cai, J .; Davies, A. G. J . Chem. Soc., Perkin Trans.1 1992, 3383.
(14) Matarasso-Chiroukhine, E.; Cadiot, P. Can. J . Chem. 1983, 61,
2476.

Addition of Substituted Stannanes to Carbonyl Compounds
Sch em e 2
J . Org. Chem., Vol. 66, No. 23, 2001 7813
Ta ble 1. Syn th esis of Tetr a a llylic Sta n n a n es (2a -c)
of the tetraallylic stannane in either polar protic or polar
aprotic solvents, suggesting an ion-pair mechanism was
unlikely. We have therefore proposed an eight-membered
transition state involving tin-solvent coordination and
concomitant H-bonding activation of the aldehyde. The
present study confirms regiospecific addition with allylic
rearrangement for the allylic stannanes studied, even for
the highly hindered substrate 2c, which is consistent
with this cyclic mechanism. An equivalent activated
species can be drawn for the HCl- and DDS-promoted
reactions. With respect to the stereochemistry of addition,
there are no clear stereoisomeric preferences or trends
that can be unambiguously assigned to a particular
transition state conformation (Scheme 3). This is perhaps
not surprising if the transition state does indeed resemble
a flexible, eight-membered heterocycle.
allylic halide
tetraallylic stannane
yielda (%)
1a
1b
1c
2a
80
94
88
2bb
2c
a
b
Isolated yield. Consists of five diastereomers (Figure 1).
Ta ble 2. Rea ction of Tetr a a llylic Sta n n a n es 2a -c w ith
Ald eh yd es 3 a n d Selected Dim eth yl Aceta ls 4
aldehyde/
acetal
yieldc
(%)
entry stannane
methoda product ratiob
1
2
3
4
5
6
7
8
9
2a
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2b
2c
2c
2c
2c
2c
2c
2c
2c
3a
3b
3c
3d
3e
3f
A
A
A
A
A
A
E
5a
5b
5c
5d
5e
5f
5d
5e
99
92
90
94
88
66
75
trace
77
72
78
86
67
68
90
83
80
92
88
71
71
77
82
65
4d
4e
3a
3b
3b
3b
3c
3c
3c
3d
3d
3d
3d
3e
3e
3e
3e
3f
The corresponding reactions of tetrapropargylic and
tetraallenic stannanes are not so invariably regiospecific.
There is no literature precedence for SE, rather than SE′,
electrophilic cleavage of allylic stannanes, which suggests
to us allylic rearrangement of either the starting stan-
nanes or product alcohols. Treatment of the starting
stannanes under the reaction conditions does not result
in any isomeric chang,e and so, regioleakage resulting
from allene-propargyl isomerization of the product al-
cohols seems a likely possibility.
E
B
B
C
D
A
B
D
A
B
C
D
A
B
C
D
B
C
D
E
6a + 7a 38:62
6b + 7b 45:55
6b + 7b 54:46
6b + 7b 63:37
6c + 7c 65:35
6c + 7c 57:43
6c + 7c 54:46
6d + 7d 50:50
6d + 7d 55:45
6d + 7d 60:40
6d + 7d 62:38
6e + 7e 56:44
6e + 7e 59:41
6e + 7e 49:51
6e + 7e 52:48
6f + 7f
6f + 7f
6f + 7f
6d + 7d 61:39
6e + 7e
8a
8b
8c
8d
8e
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
We also briefly examined the TFA catalyzed addition
of dimethylacetals 4 and stannanes 2a -c; however, the
expected allylated products were only observed in the
case of 4d (Table 2, entries 7, 27, and 35), and only trace
quantities were observed with 4e (Table 2, entries 8, 28,
and 36). Additionally, the isolated yields are also lower
than those observed with the parent aldehyde, e.g., with
benzaldehyde 3d affords 5d 94% (Table 2, entry 4),
whereas the corresponding reaction with 4d affords 5d
75% (Table 2, entry 7). Notwithstanding this, the ally-
lation of 4d and related compounds has possible synthetic
utility for unstable aldehydes.9,10
57:43
60: 40 72
3f
3f
67:33
80
71
trace
64
78
70
82
74
62
4d
4e
3a
3b
3c
3d
3e
3f
E
D
D
D
D
D
D
E
8f
8d
8e
Rea ction of Tetr a llylic Sta n n a n es 2a -c w ith
Eth yl P yr u va te 9a . Given the success of these allylation
reactions with aldehydes, we also investigated the reac-
tion of 2a -c with activated ketones, specifically with
ethyl pyruvate (9a ) (Scheme 3).
4d
4e
56
trace
E
a
Methods: (A) MeOH, rt, 4-24 h; (B) MeOH, reflux, 48 h; (C)
MeOH + DDS, reflux, 24 h; (D) THF/HCl, rt, 24 h; (E) MeOH/
TFA, rt, 24 h. Ratios determined by 1H NMR and 13C NMR.
b
c Isolated yields.
For simplicity in analysis, the mixture of methyl and
ethyl ester-formed esters (trans-esterification) were sa-
ponified with NaOH and subsequently neutralized with
HCl to afford the corresponding acids in good to excellent
yields (Table 3). However, only poor diastereoselctivity
was apparent with 2b; essentially equal quantities of syn
(11) and anti (12) products were observed.
We have previously noted that the solvent-promoted
addition of tetraallylic stannanes to aldehydes requires
a protic solvent and does not proceed in polar, aprotic
solvents such as dimethyl sulfoxide.5b This previous study
also noted no observable, structural change on solvation

7814 J . Org. Chem., Vol. 66, No. 23, 2001
McCluskey et al.
Sch em e 3
Ta ble 3. Rea ction of Tetr a a llylsta n n a n es 2a -c w ith
Each tetraorganostannane was obtained as a single
Eth yl P yr u va te 9a
regioisomer determined by the substitution pattern of
starting propargylic halide (Table 4). Thus, propargylic
halides 14c and 15c,d with a methyl/ethyl group at the
terminal position yielded tetrapropargylic stannanes
stannane
methoda
product
ratiob
yieldc (%)
2a
2b
2b
2c
A
A
D
D
10
79
64
70
49
11/12
11/12
13
56:44
46:54
(15) NMR data for tetra(2-butenyl)stannane 2b. 1H NMR (CDCl3):
δ 1.59 (br, s, J (119Sn) ) 19.0 Hz, 12H), 1.67 (br s, J (119Sn) ) 77.8 Hz,
J (117Sn) ) 59.4 Hz, 8H), 1.71 (br s, J (119Sn) ) 24.9 Hz, 12H), 5.28 (m,
4H). 13C NMR: cis,cis,cis,cis [δ(J (117Sn), J (119Sn))] 10.60 (240.4, 251.1),
12.51, 118.87 (50.2), 128.00 (48.4); cis,cis,cis,trans 11.09 (240.3, 251.8),
12.51, 14.51a (255.6, 267.0), 17.92a (13.08), 119.01 (49.7), 121.10a (51.9),
128.06 (48.6), 128.87a (48.2); cis,cis,trans,trans 11.09 (240.3, 251.8),
12.51, 14.78a (254.9, 267.0), 17.92a (13.08), 119.16 (49.7), 121.22a (51.9),
128.13 (48.9), 128.94a (47.8); cis,trans,trans,trans 11.30 (241.2, 251.9),
12.51, 15.01a (254.8, 267.1), 17.92a (13.08), 119.32 (50.2), 121.34a (51.9),
128.20 (48.5), 129.01a (48.1); trans,trans,trans,trans 15.23 (255.6,
267.8), 17.92 (13.08), 121.46 (52.5), 129.09 (48.7). Note a ) trans butenyl
units
a
Methods: (A) MeOH, rt, 4-24 h; (D) THF/HCl, rt, 24 h.
Ratios determined by 1H NMR and 13C NMR. c Isolated yields.
b
Syn th esis of Tetr a a llen ic a n d -p r op a r gylic Sta n -
n a n es 16a ,c a n d 17c,d . Tetraallenic 16 and tetrapro-
pargylic 17 stannanes were prepared, in moderate yields,
from the corresponding propargylic chlorides 14 and
bromides 15 by a Grignard reaction in the presence of a
catalytic amount of HgCl2 (ca. 2 mol %) (Scheme 4).16
(16) Dabdoub, M. J .; Rotta, J . C. G. Synlett 1996, 526.

Addition of Substituted Stannanes to Carbonyl Compounds
J . Org. Chem., Vol. 66, No. 23, 2001 7815
Ta ble 5. Rea ction of Tetr a a llen ic (16a ,c) a n d
-p r op a r gylic Sta n n a n es (17c,d ) w ith Ald eh yd es a n d
Aceta ls
Sch em e 4
aldehyde/
acetal
yieldc
(%)
entry stannane
methoda product
ratiob
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
16a
16a
16a
16a
16a
16a
16a
16a
16a
16a
16a
16c
16c
16c
16c
17c
17c
17c
17c
17c
17c
17c
17d
17d
17d
17d
17d
3a
3a
3c
3c
3d
3d
3e
3e
3g
4d
4e
3c
3d
3e
3g
3a
3c
3d
3e
3g
4d
4e
3a
3c
3d
3e
3g
A
D
A
D
A
D
A
D
A
E
18a /19a
18a /19a
18c/19c
18c/19c
18d /19d
18d /19d
18e/19e
18e/19e
18g/19g
18d /19d
18e/19e
20c/21c
20d /21d
20e/21e
30:70
28:72
30:70
35:65
25:75
50:50
27:73
54:46
81:19d
0:100
0:100
85:15
63:37
74:26
77
85
78
86
79
88
79
86
73
74
78
88
84
80
72
75
85
87
77
75
81
79
79
82
81
83
76
Ta ble 4. Syn th esis of Tetr a a llen ic a n d -p r op a r gyic
Sta n n a n es (16a ,c a n d 17c,d )
tetraallenic and propargylic
E
propargyl halide
stannanes
yielda (%)
A
A
A
A
A
A
A
A
A
E
14a
15a
14b
15b
14c
15c
15d
16a
16a
16cb
16cb
17c
17c
17d
61
61
59
63
61
62
55
20g/21g 82e:18f
22a /23a
22c/23c
22d /23d
22e/23e
89:11
90:10
83:17
94:6
22g/23g 90g:10h
22d /23d 100:0
22e/23e 100:0
a
b
Isolated yields. Consists of three diastereomers in the ratio
50:37:13 as determined by 119Sn NMR spectroscopy.
E
A
A
A
A
A
24a /25a
24c/25c
24d /25d
24e/25e
88:12
93:7
91:9
92:8
Sch em e 5
24g/25g 90i:10
a
Methods: (A) MeOH, rt, 4-24 h; (D) THF/HCl, rt, 24 h; (E)
MeOH/TFA, rt, 24 h. Ratios determined by 1H NMR and 13C
b
NMR. c Isolated yields. Two diastereomers (68:13) were observed
d
in the 13C NMR spectrum. e Two diastereomers (68.4:12.8) of 19 g
were observed in the 13C NMR spectrum. f Two diastereomers (52:
30) were observed in the 13C NMR spectrum. g Two diastereomers
(46.4:43.8) were observed in the 13C NMR spectrum. Two dia-
h
stereomers (7.0:2.8) were observed in the 13C NMR spectrum. i Two
diastereomers (74.8:15.0) were observed in the 13C NMR spectrum.
The addition of aldehydes to tetrapropadienylstannane
16a was regioselective in favor of the allylically rear-
ranged homopropargylic alcohols 19 but contaminated
with up to 30% of the isomeric allenyl alcohols 18. Tetra-
(1,2-butadienyl)tin 16c, however, reacted exclusively with
allylic rearrangement to provide diastereomeric homo-
propargylic alcohols 20 (syn) and 21 (anti) with a
predominance of the former (Table 5, entries 12-15, de
) 26-70%). Tetra(2-butynyl)tin 17c yielded a mixture
of regioisomers favoring the allylically rearranged allenyl
alcohols 22 over the homopropargylic alcohols 23.
17c,d while the other propargylic halides not substituted
at this position provided tetraallenic stannanes 16a or
16c exclusively. Propargylic triarylstannanes are re-
ported to isomerize in methanol to the corresponding
allenyl isomer depending on the substitution pattern.17
No isomerization of 16a , 16c, 17c, or 17d was observed
in methanol after 48 h at room temperature, suggesting
that the Grignard reaction yields the thermodynamically
favored product in each case.
Rea ction s of Tetr a a llen ic- a n d -p r op a r gylic Sta n -
n a n es (16a ,c a n d 17c,d ) w ith Ald eh yd es 3 a n d
Aceta ls 4. As with 2a -c, the corresponding reactions of
tetraallenic stannanes 16a ,c and tetrapropargylic stan-
nanes 17c,d with aldehydes 3 (Scheme 5) in methanol
at room temperature and with HCl/THF in a limited
number of cases were also examined. As expected the
room temperature reaction typically proceeded cleanly
and in good to excellent yields (Table 5, entries 1, 3, 5, 7,
9, 12-20, and 23-27, 72-88%).
Reactions of 16a and aldehydes conducted in HCl/THF
also proceeded smoothly (Table 5, entries 2, 4, 6, and 8),
with modest improvements in reaction yields compared
with equivalent reactions conducted at room temperature
in methanol. For example, the reaction of 16a with 3d
in methanol affords 18d + 19d in a 79% yield (Table 5,
entry 5, 25:75), whereas in HCl/THF 18d + 19d were
isolated in an 88% yield (Table 5, entry 6, 50:50).
Interestingly, with aromatic aldehydes (3d and 3e)
reactions conducted in acidic media show preferential
formation of the rearranged proparagylic isomers 19,
increasing from 25 to 50% (Table 5, entries 5 and 6
respectively) of the reaction mixture (compared with
methanol). The corresponding acetal reactions afford 19d
and 19e exclusively (Table 5, entries 10 and 11).
With 17c, the corresponding TFA-mediated additions
to acetals 4d and 4e also gave rise to a single isomeric
(17) Lequan, M. M.; Guillerm, G. Hebd. Seances Acad. Sci. Ser. C
1969, 268, 858; Chem. Abstr. 1969, 70, 115280d.

7816 J . Org. Chem., Vol. 66, No. 23, 2001
McCluskey et al.
Exp er im en ta l Section
Sch em e 6
Ma ter ia ls. All reagents were of commercial quality and
were used as received (Aldrich). Solvents were dried and
purified using standard techniques. Reactions were monitored
by TLC, on aluminum plates coated with silica gel with
fluorescent indicator (Merck 60 F254). Boiling points are
uncorrected. Unless otherwise noted, NMR spectra were
recorded in CDCl3 at 200, 300 or 400 MHz for 1H and at 50,
75 MHz for 13C (Varian Gemini 200 MHz, Bruker Avance
300MX, Varian Unity 400 MHz). Elemental analyses were
determined by the University of Strathclyde Microanalysis
service and the University of Queensland Microanalysis
Service. Mass spectra (m/e) were obtained in the EI (70 eV)
mode at the Organic Mass Spectrometry Facility at the
University of Tasmania using a Kratos Analytical Concept ISQ
high-resolution mass spectrometer.
Gen er a l P r oced u r e for Rea ction of Tetr a a llylic, -a l-
len ic, a n d -p r op a r gylic Sta n n a n es w ith Ca r bon yl Com -
p ou n d s. Meth od A. The stannane (1.0 mmol) and aldehyde
3 (4.0 mmol) were dissolved in methanol (4 mL) and the
mixture stirred at room temperature (ca. 25 °C) for ap-
proximately 16-24 h (overnight). Water (10 mL) was then
added, and the resulting white precipitates were allowed to
settle. The solvent was filtered and the solid was washed with
dichloromethane (2 × 10 mL). The aqueous methanol was then
extracted with dichloromethane (3 × 15 mL) and the combined
organic extracts were dried over Na2SO4 and concentrated in
vacuo. The crude allylated product was purified by distillation.
Ta ble 6. Rea ction of Tetr a a llen ic (16a ,c) a n d
-p r op a r gylic Sta n n a n es (17c,d ) w ith Activa ted Ca r bon yl
Com p ou n d s 9a a n d 9b
stannane ketone methoda
product
ratiob
yield (%)
16a
16a
16c
16c
17c
17d
9a
9b
9a
9b
9a
9b
A
B
A
B
A
A
26a /27a
26b/27b
28a /29a
28b/29b
30a /31a
32a :33a
74:26
64:34
63:37
54c
36
Meth od B. The stannane (1.0 mmol) and aldehyde 3 (4.0
mmol) were dissolved in methanol (4 mL) and refluxed for 48
h. Water (10 mL) was then added and the resulting white
precipitate allowed to settle. The mixture was filtered, and the
solid was washed with dichloromethane (2 × 10 mL). The
aqueous methanol was then extracted with dichloromethane
(3 × 15 mL) and the combined organic extracts were dried
(Na2SO4) and concentrated in vacuo. The crude allylated
product was purified by distillation.
56c
38
100:0
100:0
50c
52
a
b
Methods: (A) MeOH, rt; (B) MeOH reflux. Determined by
1H and 13C NMR. c Isolated as the carboxylic acid.
product, in these instances, the allylically rearranged
allenyl alcohols 22 (Table 5, entries 21 and 22).
Meth od C. The stannane (1.0 mmol) and dimethyldimethox-
ystannane (DDS) (0.1 mmol) were dissolved in methanol (4
mL) and stirred at room temperature (ca. 25 °C) for 2 h.
Aldehyde 3 (4.0 mmol) was added, and the mixture was
refluxed for 24 h. Water (10 mL) was then added to the cooled
mixture, and the resulting white precipitates were allowed to
settle. The mixture was filtered, and the solid was washed with
dichloromethane (2 × 10 mL). The aqueous methanol was then
extracted with dichloromethane (3 × 15 mL), and the combined
organic extract was dried (Na2SO4) and concentrated in vacuo.
The crude allylated product was purified by distillation.
Rea ction of Tetr a a llen ic 16a ,c a n d P r op a r gylic
Sta n n a n es 17c,d w ith Eth yl P yr u va te 9a a n d Cy-
cloh exa n on e 9b. We have also examined the reactions
of tetra- allenic 16a ,c and propargylic stannanes 17c,d
with activated ketones, with ethyl pyruvate (9a ), and
cyclohexanone (9b) (Scheme 6).
Again, for simplicity in analysis, the reactions involving
additions to ethyl pyruvate (9a ) were saponified with
NaOH and subsequently neutralized with HCl to afford
the corresponding acids in good to excellent yields (Table
6). With 16a , moderate yields and moderate selectivities
were noted with the major homopropargylic alcohol 26
being contaminated with up to 34% of the homoallenyl
alcohol 27, with both 9a and 9b. No such contamination
was observed with 16c, with these additions giving rise
to moderate diastereoselectivity of syn (28) versus anti
(29), and no allenyl alcohol products were observed. A
single product, 28, was isolated after addition of 16c to
9b. Addition of 17c and 17d to ethyl pyruvate afforded
exclusively the allenyl alcohols 30a and 32a , respectively.
Meth od D. The stannane (1.0 mmol) and aldehyde 3 (4.0
mmol) were dissolved in THF (4 mL). A solution of HCl (0.5
mL, 2 N) was added, and the mixture was stirred at room
temperature (ca. 25 °C) for 24 h. A solution of saturated sodium
hydrogen carbonate NaHCO3 (10 mL) was added, and the
aqueous THF was then extracted with dichloromethane (3 ×
15 mL) and the combined organic extract was dried (Na2SO4)
and concentrated in vacuo. The crude allylated product was
purified by distillation.
Meth od E. The stannane (1.0 mmol) and acetal 4 (4.0
mmol) were dissolved in methanol (4 mL). TFA (0.5 mL) was
added, and the mixture was stirred at room temperature (ca.
25 °C) for 24 h. A solution of saturated sodium hydrogen
carbonate NaHCO3 (10 mL) was added. The aqueous methanol
was then extracted with dichloromethane (3 × 15 mL), and
the combined organic extract was dried (Na2SO4) and concen-
trated in vacuo. The crude allylated product was purified by
distillation.
Con clu sion s
We have developed experimentally simple, high yield-
ing and atom economic procedures for the selective
addition of unsaturated carbon fragments to carbonyl
compounds under a variety of extremely mild conditions.
Diastereoselectivities are low, but regioselectivity is
generally high, with addition to the γ-position of the
allylic triad.
Allyla tion P r od u cts. Homoallylic, -allenic, and -propar-
gylic alcohols (5-8, 10-13, and 18-33) obtained herein were
characterized by 1H and 13C NMR spectroscopy, microanalysis,
and high-resolution mass spectrometry (where appropriate),
and by comparison with literature values: 5a ,18 5b,19 5d ,20 5f,21

Addition of Substituted Stannanes to Carbonyl Compounds
J . Org. Chem., Vol. 66, No. 23, 2001 7817
6a ,18b 7a ,18b 6b,22 7b,22 6c,23 7c,23 6d ,24 7d ,24 6f,25 7f,25 8a ,18a
8b,26 8d ,22,26 8f,27 11,28 12,29 18a ,29 19a ,29 18c,30 19c,30 18d ,20a,31
19d ,20a,31 18e,32 19e,32 20c,33 21c,33 20d ,34 21d ,34 24d ,35 25d ,35
26b,34 27b,34 28b,34 29b.34
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Ack n ow led gm en t. Financial support from the Aus-
tralian Research Council (D.Y.) and from the University
of Newcastle (A.McC).
Su p p or tin g In for m a tion Ava ila ble: Experimental de-
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at http://pubs.acs.org.
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