Reversible stereocontrol in the Lewis acid promoted reaction of alkoxyaldehydes toward various allyltins

Article abstract of DOI:10.1016/S0040-4039(02)02867-8

In the reactions of variously substituted allyltin reagents toward achiral alkoxyaldehydes, one of the diastereomeric homoallyl alcohols was stereoselectively obtained by the help of BF₃, while TiCl₄ preferentially gave the other dia

Full text of DOI:10.1016/S0040-4039(02)02867-8

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 1405–1408
Reversible stereocontrol in the Lewis acid promoted reaction of
alkoxyaldehydes toward various allyltins
Yutaka Nishigaichi* and Akio Takuwa
Department of Material Science, Faculty of Science and Engineering, Shimane University, 1060 Nishikawatsu-cho, Matsue,
Shimane 690-8504, Japan
Received 21 November 2002; revised 17 December 2002; accepted 19 December 2002
Abstract—In the reactions of variously substituted allyltin reagents toward achiral alkoxyaldehydes, one of the diastereomeric
homoallyl alcohols was stereoselectively obtained by the help of BF , while TiCl preferentially gave the other diastereomer,
3
4
though (E)- and (Z)-3-monoalkylallyltin reagents were exceptional. This reversible diastereoselectivity can be explained by the
coordination geometry (anti or syn) of the Lewis acids toward alkoxyaldehydes. © 2003 Elsevier Science Ltd. All rights reserved.
Reaction between aldehydes and allyltin reagents is
known as a useful synthetic method to control
direction to the coordinated Lewis acid. Thus, we were
stimulated to investigate the relation between the coor-
dination site of the Lewis acid and the stereoselectivity
using simple achiral alkoxyaldehydes to control the
coordination.
1
diastereoselectivity. One of the most mentioned selec-
2
tivities is referred to as prochirality matching. For
example, the syn-selectivity for the Lewis acid-pro-
moted reaction between an achiral aldehyde and 3-
3
mono-substituted allylic tin reagents such as crotyltin
At first, a-benzyloxyacetaldehyde 1 as a most simple
alkoxyaldehyde was employed. As a non-chelative
Lewis acid, BF ·Et O was used. On the other hand, for
is the most representative. As generally accepted, the
characteristic feature of this selectivity is that it is not
affected seriously by the cis/trans-geometry of the
3
2
a
chelation controlled reaction, TiCl ·2Et O was
4 2
4
reagent and the coordination mode of the applied
employed, which is known to be effective to suppress
the SnꢀTi transmetallation. Allyltins investigated here
were (Z)-3-deuterioallyltin (2a)
(E)-crotyltin (2b), (Z)-pentenyltin (2c) and (E)-cin-
namyltin (2d) as 3-mono-substituted ones, and ger-
anyltin (2e) and neryltin (2f) as 3,3-disubstituted ones.
The results are collected in Table 1.
5
9
Lewis acid, chelation or non-chelation. This is one
7,10
reason why the methodology has been widely applied to
the stereoselective organic synthesis.
as unsubstituted one,
11
In contrast to the current understanding, we will
describe here that such Lewis acid promoted reactions
of various allylic tin reagents toward achiral
alkoxyaldehydes are often affected by the coordination
mode of the Lewis acid and the selectivity can be
controlled efficiently by the applied Lewis acid.
In the BF -promoted reactions (entries 1–6), most of
3
variously substituted allylic tins exhibited good to high
stereoselectivity (product 3), which is parallel to the
previously reported results for non-chelative alde-
1,6,12
Recently, we have reported stereospecific nature of the
hydes.
One exception was the reaction of (Z)-
6
Lewis acid promoted reaction of 3,3-disubstituted and
reagent 2c (entry 3). Its low syn-selectivity (product 4)
7
3
-deuterated allyltin reagents toward aldehydes. This
was also similar to the previous result reported by
5b
stereospecificity was accounted by the syn-synclinal
Keck.
5
b,8
transition state
where the allyltin reagent was
assumed to approach the aldehyde from the opposite
Interestingly, the TiCl -promoted reactions (entries 7–
4
1
2) showed essentially opposite and good to high
stereoselectivity (product 4), except for the reaction of
b (entry 8) which underwent an unselective reaction.
2
Keywords: allylation; chelation; diastereoselection; stereocontrol; tin
and compounds.
(
Z)-Reagent 2c, in this case (entry 9), behaved like
*
Corresponding author. Fax: +81 852 326429; e-mail: nishigai@
other reagents and exhibited much higher diastereose-
riko.shimane-u.ac.jp
lectivity of 4 compared with entry 3. Because the TiCl4-
0
040-4039/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(02)02867-8

1
406
Y. Nishigaichi, A. Takuwa / Tetrahedron Letters 44 (2003) 1405–1408
Table 1. Reactions between benzyloxyacetaldehyde and various allyltins
Allyltin reagent
[Entry] Product ratio, 3/4 (yield/%)
E
Z
a
b
R , R
R
BF ·Et O
TiCl ·2Et O
3
2
4
2
H, D
Me, H
H, Et
Ph, H
Ph
Bu
2a
2b
2c
2d
2e
2f
[1] 89/11 (quant.)
[2] 85/15 (69)
[3] 34/66 (72)
[4] 90/10 (87)
[5] 96/4 (90)
[7] 20/80 (quant.)
[8] 50/50 (69)
[9] 9/91 (67)
[10] 3/97 (80)
[11] 1/99 (83)
[12] B1/99 (75)
Me CꢁCHCH CH , Me
2
2
2
Me, Me CꢁCHCH CH
[6] 95/5 (83)
2
2
2
a
To a mixture of 1 (0.2 mmol) and 2 (0.3 mmol) in CH Cl (2 mL) was added BF ·Et O (0.4 mmol) at −78°C under N . The mixture was stirred
2
2
3
2
2
for 2 h at the same temperature and then quenched with an aqueous NaHCO3 solution. The CH Cl extract was dried (Na SO ) and
2
2
2
4
concentrated, and the products were isolated by TLC.
b
To a solution of 1 in CH Cl (1 mL) were added Et O (0.4 mmol) and TiCl (0.2 mmol) successively at −78°C under N . After 5 min, 2 (0.3
2
2
2
4
2
mmol) in CH Cl2 (1 mL) was added and the mixture was stirred for 2 h at −78°C. The work-up procedure was the same as above.
2
promoted reaction was highly regioselective in every
case and the diastereoselectivity was stereospecific as
typically shown by the reactions of 2a (entry 7), 2e
oxy one 6, and aromatic one 7, were employed to
the reactions with 3-mono-substituted cinnamyltin 2d
and 3,3-disubstituted neryltin 2f (Table 2). BF -medi-
3
12
(
entry 11), and 2f (entry 12), the influence of the
ated reactions with 2d gave the syn-isomers 3 in
good selectivity (entries 1, 3, and 5) as for the reac-
transmetallated allyltitanium species could be
excluded.
tion of 1. The corresponding TiCl
depended on aldehydes: aldehydes 5 (entry 2) and 7
entry 6), which formed six-membered chelates,
showed good anti-selectivity to give 4, while aldehyde
(entry 4) which lead to a seven-membered chelate
-mediated reactions
4
(
In addition, it is noteworthy that in the reactions of
non-chelative heptanal with 2d and 2e (Scheme 1), the
both Lewis acids gave preferentially the same
stereoisomers in more than 90% selectivity which cor-
responded to the diastereomer 3.
6
gave preferentially the syn-product 3.
On the other hand, in the reactions with 2f, all alde-
hydes 5–7 exhibited the binary stereoselectivity
These results suggest that the present binary stere-
ocontrol especially in the cases of 2a, 2d–f was
achieved by the benzyloxy substituent. Because benzyl-
(
entries 7–12). It is interesting that seven-membered
chelate of 6 also preferred the product 4 in this case
entry 10). Here again, BF -mediated reactions fol-
(
3
oxyacetaldehyde simply coordinates BF3 as
a
lowed the previously reported diastereoselectivity for
monodentate ligand, the complex takes anti-
6
1
3
the non-chelative aldehydes.
conformation (Scheme 2, A). On the other hand,
because TiCl4 can take two more ligands, the
alkoxyaldehyde chelates it as a bidentate ligand to
In conclusion, the binary diastereoselectivity in the
reaction between alkoxyaldehydes and allyltin
reagents 2a and 2d–f could be controlled by the
applied Lewis acid, of which coordination mode is
critical for the selectivity. While there are some limi-
14
form
a
cyclic complex, i.e. syn-conformation
(
Scheme 2, B). Then, if an allylic tin reagent comes
from the opposite direction to the coordinating Lewis
acid to afford the syn-synclinal conformation as pro-
tations such as BF -mediated reaction of 2c and
8a
3
posed for the reaction of an allylsilicon reagent,
TiCl -mediated reactions of 2b and of 2d with 6 of
4
diastereomer 3 or 4 would be selectively obtained
from the complex A or B via the transition structure
C or D, respectively. In contrast to these cases, the
exceptional behaviour of 3-monoalkyl-substituted
allyltin reagents 2b and 2c can not be fully explained
which reasons are still ambiguous, this methodology
is synthetically useful due to the flexible stereocontrol.
8
a
so far. But, as pointed out previously, the transition
structures C% and D% which give the other
diastereomers may be included especially in the cases
of entries 3 and 8.
Next, to clarify the scope of the reaction, various
alkoxyaldehydes such as b-benzyloxy one 5, g-benzyl-
Scheme 1. Reactions of heptanal.

Y. Nishigaichi, A. Takuwa / Tetrahedron Letters 44 (2003) 1405–1408
1407
Scheme 2. Plausible reaction pathways.
Table 2. Reactions between various alkoxyaldehydes and allyltins 2d and 2f
Alkoxyaldehyde
Lewis acid
[Entry] Product ratio, 3/4 (yield/%)
with 2f
with 2d
3
-Benzyloxypropanal (5)
-Benzyloxybutanal (6)
BF ·Et O
[1] 96/4 (55)
[7] 90/10 (55)
[8] 7/93 (52)
[9] 85/15 (80)
[10] 30/70 (82)
[11] 68/32 (92)
[12] 17/83 (83)
3
2
TiCl ·2Et O
[2] 4/96 (quant.)
[3] \99/1 (80)
[4] 75/25 (69)
[5] 79/21 (98)
[6] 29/71 (85)
4
2
4
BF ·Et O
3
2
TiCl ·2Et O
4
2
o-Anisaldehyde (7)
BF ·Et O
3 2
TiCl ·2Et O
4
2
Acknowledgements
1990, 1161; (b) Marshall J. A.; Wang, X. J. Org. Chem.
992, 57, 1242.
1
This work was partly supported by a Grant-in-Aid for
Scientific Research (No. 12640519) from the Japanese
Ministry of Education, Culture, Sports, Science and
Technology.
5. (a) Keck, G. E.; Boden, E. P. Tetrahedron Lett. 1984, 25,
1879; Keck, G. E.; Abbott, D. E. Tetrahedron Lett. 1984,
25, 1883; Keck, G. E.; Abbott, D. E.; Wiley, M. R.
Tetrahedron Lett. 1987, 28, 139; (b) Keck, G. E.; Savin,
K. A.; Cressman, E. N. K.; Abbott, D. E. J. Org. Chem.
1
994, 59, 7889.
. Nishigaichi, Y.; Takuwa, A. Tetrahedron Lett. 1999, 40,
09.
. Nishigaichi, Y.; Takuwa, A. Tetrahedron Lett. 2002, 43,
045.
References
6
7
8
1
1
. (a) Yamamoto, Y.; Asao, N. Chem. Rev. 1993, 93, 2207;
b) Nishigaichi, Y.; Takuwa, A.; Naruta, Y.; Maruyama,
K. Tetrahedron 1993, 49, 7395.
. Marshall, J. A. Chem. Rev. 1996, 96, 31.
. Yamamoto, Y.; Yatagai, H.; Naruta, Y.; Maruyama, K.
J. Am. Chem. Soc. 1980, 102, 7107.
. For exceptional cases, see: (a) Mikami, K.; Kawamoto,
(
3
. (a) Bottoni, A.; Costa, A. L.; Tommaso, D. D.; Rossi, I.;
Tagliavini, E. J. Am. Chem. Soc. 1997, 119, 12131; (b)
Denmark, S. E.; Weber, E. J. J. Am. Chem. Soc. 1984,
106, 7970; Denmark, S. E.; Weber, E. J.; Wilson, T. M.;
Willson, E. M. Tetrahedron 1989, 45, 1053.
2
3
4
K.; Loh, T.-P.; Nakai, T. J. Chem. Soc., Chem. Commun.

1
408
Y. Nishigaichi, A. Takuwa / Tetrahedron Letters 44 (2003) 1405–1408
9
. Nishigaichi, Y.; Yoshikawa, M.; Takigawa, Y.; Takuwa,
A. Chem. Lett. 1996, 961.
0. Orain, D.; Guillemin, J.-C. J. Org. Chem. 1999, 64,
563.
12. Nishigaichi, Y.; Takuwa, A. Chem. Lett. 1994, 1429.
13. Corey, E. J.; Lee, T. W. Chem. Commun. 2001, 1321 and
references cited therein.
14. Santelli, M.; Pons, J.-M. Lewis Acids and Selectivity in
Organic Synthesis; CRC Press: Boca Raton, 1996 and
references cited therein.
1
1
3
1. Nishigaichi, Y.; Ishida, N.; Takuwa, A. Bull. Chem. Soc.
Jpn. 1994, 67, 274.