Addition of lactate-derived chiral allyltrichlorostannanes to chiral aldehydes

Article abstract of DOI:10.1016/j.tetlet.2004.09.186

Chiral lactate-derived allyltrichlorostannanes reacted with chiral α-methyl, β-alkoxy and syn and anti α-methyl-β-alkoxy aldehydes to give the corresponding homoallylic alcohols with moderate to high 1,4-syn-diastereoselectivities. Chiral lactate-derived allyltrichlorostannanes reacted with chiral α-methyl β-alkoxy and syn and anti α-methyl-β-alkoxy aldehydes to give the corresponding homoallylic alcohols with moderate to high 1,4-syn-diastereoselectivities.

Full text of DOI:10.1016/j.tetlet.2004.09.186

Tetrahedron
Letters
Tetrahedron Letters 45 (2004) 8835–8841
Addition of lactate-derived chiral allyltrichlorostannanes to
chiral aldehydes
Luiz C. Dias* and Leonardo J. Steil
´
Instituto de Quımica, Universidade Estadual de Campinas, UNICAMP, C.P. 6154, 13084-971 Campinas, SP, Brazil
Received 13 September 2004; accepted 30 September 2004
This paper is dedicated to Professor Edmundo A. Ru´veda on the occasion of his 70th birthday
Abstract—Chiral lactate-derived allyltrichlorostannanes reacted with chiral a-methyl b-alkoxy and syn and anti a-methyl-b-alkoxy
aldehydes to give the corresponding homoallylic alcohols with moderate to high 1,4-syn-diastereoselectivities.
ꢀ 2004 Elsevier Ltd. All rights reserved.
The Lewis-acid mediated reaction of allylsilanes and
allylstannanes with aldehydes is a well-known procedure
for the preparation of homoallylic alcohols.1 Because
these reactions complement the aldol reactions, allylsi-
lanes and allylstannanes are among the most important
groups of organometallic-type reagents available for the
control of acyclic stereochemistry.2 The addition of eno-
lates or analogs bearing a stereogenic center is of great
importance in the application of the aldol addition to
synthesis. We recently communicated that in situ pre-
pared chiral allyltrichlorostannanes react with chiral
a-methyl, chiral b-alkoxy as well as syn and anti a-
methyl-b-alkoxy aldehydes to give 1,4-syn homoallylic
alcohols that are key intermediates for the preparation
of polyacetate and polypropionate-derived natural
products.3–11 We have described also that chiral and
achiral allyltrichlorostannanes react with N-Boc-a-ami-
noaldehydes to give 1,2-syn N-Boc-a-aminoalcohols
that are important intermediates for the preparation of
hydroxyethylene dipeptide isosteres.3–11
asymmetric induction in lactate-derived allyltrichloro-
stannane reactions with b-alcoxy and a-methyl-b-alkoxy
aldehydes under conditions that preclude internal chela-
tion with the aldehyde b-alkoxy substituent. This study
details our efforts to understand the double stereodiffer-
entiating stereocontrol elements involved in chiral allyl-
trichlorostannane additions to chiral aldehydes. Chiral
allylsilane (S)-2 and (R)-2 were prepared from benzyl-
protected methyl lactate ester 1, both enantiomers of
which are commercially available (Scheme 1).14,15
According to previously established experimental proce-
dures, allylsilane 2 was mixed with SnCl4 before the
addition of a solution of the aldehyde in order to pro-
mote the ligand exchange reaction leading to the corre-
sponding allyltrichlorostannane 3 (Scheme 1).5
Aldehydes (S)-4 and (S)-5 were prepared in excellent
yields from (3S)-1,3-butanediol and methyl 3-hydroxy-
(2S)-methyl-propionate, respectively.11 The 1,2-syn and
1,2-anti aldehydes (2R,3S)-6 and (2S,3S)-7 were easily
prepared by using syn16 and anti17 selective aldol reac-
tions, respectively, as the key steps.11 These substrates
We wish to describe here a divergently stereocontrolled
reaction between chiral aldehydes and chiral lactate-
derived allyltrichlorostannanes to give homoallylic alco-
hols with moderate to high diastereoselectivities.12 In
this part of the investigation, we have examined the
interplay between 1,2-(Felkin–Anh),13 1,3- and 1,4-
1. TMSCH2MgCl
Cl
Cl
Cl
Sn
CeCl , THF, -780C
3
TMS
O
SnCl4
OBn
o
OBn
OBn
CH2Cl2, -60 C
MeO
2. SiO2
n-hexane, 93%
1
2
Me
3
Me
Me
Keywords: Allyltrichlorostannes; Chiral allylsilanes; 1,4-Asymmetric
induction.
+
Me3SiCl
*
Corresponding author. Tel.: +55 019 3788 3021; fax: +55 019 3788
3023; e-mail: ldias@iqm.unicamp.br
Scheme 1.
0040-4039/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2004.09.186

8836
L. C. Dias, L. J. Steil / Tetrahedron Letters 45 (2004) 8835–8841
have been selected to be representative of the complex
fragments that might be coupled in polyacetate and
polypropionate-derived aldol-type reactions. For these
aldehydes, internal chelation is presumably prevented
by use of bulky silyl protecting groups since, with few
exceptions, silyl ethers are generally recognized for their
poor coordinating and chelating abilities.18,19
formation of the 1,2-syn diastereomer, with a small pref-
erence for aldehyde Si-face attack (Felkin addition).13
We next examined the stereochemical impact of both a
and b-aldehyde substituents with chiral syn- and anti-
disubstituted a-methyl-b-alkoxy aldehydes. Before start-
ing the study described in Scheme 3, we expected that
under conditions that preclude internal chelation, the
carbonyl facial bias of syn- and anti-disubstituted alde-
hydes 6 and 7 should be highly predictable.19 For 1,2-
anti aldehyde 7, we expected high levels of asymmetric
induction since the factors which favor both 1,2- and
1,3-asymmetric induction mutually reinforce nucleophi-
lic addition to this aldehyde to give the 1,2-syn-1,3-anti
diastereomer.19 However, we observed that this is not
the case under the reaction conditions described here.
Achiral allyltrichlorostannane 8 reacted with chiral
syn-a,b-disubstituted aldehyde 6 to give the correspond-
ing 1,2-syn-1,3-syn product 11 in 92% yield, with 96:04
diastereoselectivity (Scheme 3).11,21 This example shows
that under these conditions a 1,2-syn aldehyde has a
preference to give the product with Felkin13 addition
as well as 1,3-syn addition. In the presence of an a-
methyl stereocenter, 1,3-asymmetric induction imposes
an intrinsic facial bias on the carbonyl that results in
the formation of a 1,3-syn-dioxygen relationship. This
is not observed when the a-methyl stereocenter is absent.
In order to check the facial selectivities of aldehydes 4–7,
we reacted them with achiral allyltrichlorostannane 8
(Schemes 2 and 3).11 Achiral allyltrichlorostannane 8
reacted with chiral b-alkoxy aldehyde (S)-4 in CH2Cl2
at À78ꢁC to give the corresponding 1,3-anti product 9
as the major isomer in good yield and with 78:22 diaste-
reoselectivity (Scheme 2).20,21 The stereoinduction ob-
served in this reaction indicates that the intrinsic facial
bias imposed by the resident b-OTBS substituent results
in preferential formation of the 1,3-anti diastereomer,
with a preference for aldehyde Si-face attack.
Achiral allyltrichlorostannane 8 reacted with chiral a-
methyl aldehyde (S)-5 in CH2Cl2 at À78ꢁC to give the
corresponding 1,2-syn product 10 as the major product
in good yield but with only 66:34 diastereoselectivity
(Scheme 2).11,21 The stereoinduction observed in this
reaction indicates that the intrinsic facial bias imposed
by the resident a-methyl group results in preferential
Achiral allyltrichlorostannane 8 addition to chiral anti-
a,b-disubstituted aldehyde 7 gave the corresponding
1,2-syn-1,3-anti-product 12 as the major isomer in 86%
yield, although with only 55:45 diastereoselectivity
(Scheme 3).11,21
OH
OTBS
Me
O
OTBS
Me
CH2Cl2
H
-78oC
80%
9
(S)-4
diastereoselectivity
78:22 (anti:syn)
This example shows that anti aldehyde 7 has no facial
preference under these conditions, since the Felkin addi-
tion to give 1,2-syn isomer competes with the b-alkoxy
stereocenter to give the 1,3-syn isomer. Once again, we
observed that under these allyltrichlorostannane condi-
tions in the presence of an a-methyl stereocenter, the
b-OTBS has a strong preference to give the 1,3-syn iso-
mer. One might project that the transition states of these
reactions exhibit less charge separation than the aldol
processes, and are, accordingly, less subject to the elec-
trostatic influence of the b-OTBS function.
SnCl3
8
O
OTBS
OH
OTBS
CH2Cl2
H
-78oC
80%
(S)-5
10
Me
Me
diastereoselectivity
66:34 (syn:anti)
Scheme 2.
In order to check the facial selectivity of allyltrichloro-
stannane (S)-3 we reacted it with achiral aldehydes
13a–e and observed the formation of 1,4-syn products
14a–e as the major isomers (up to >95:5 diastereoselec-
tivity) (Scheme 4 and Table 1).
OH
OTBS
O
OTBS
Me
Me
Me
CH2Cl2
H
-78oC
92%
6
11
Me
Me
Me
diastereoselectivity 96:04
The stereoselectivity of these reactions is consistent with
an intermediate allyltin trichloride, which is stabilized by
tin–oxygen interaction (Scheme 4). These reactions pro-
ceed through a closed, chair-like transition structure (A)
where good information transfer from the resident ste-
reogenic center on the allyltrichlorostannane was ex-
pected. In order to avoid steric interactions with the
methyl group, the benzyl substituent at the oxygen
would adopt a trans orientation in the five-member ring.
This intermediate reacts with the aldehyde via a chair-
like six-member ring transition state (A) in which the
SnCl3
8
OH
OTBS
Me
O
OTBS
CH2Cl2
Me
Me
-78oC, 86%
H
12
7
Me
Me
Me
diastereoselectivity 55:45
Scheme 3.

L. C. Dias, L. J. Steil / Tetrahedron Letters 45 (2004) 8835–8841
8837
Cl
Cl
Cl
Sn
BnO
R
OH
(S)-3
CH2Cl2, -78oC
82—90%
Me
O
H
Me
R
+
O
Me
H
Cl3Sn
O
14a-e
OBn
Bn
(S)
diastereoselectivity
up to >95:5
13a-e
H
R
A
Scheme 4.
Table 1. Chiral allyltrichlorostannane additions to achiral aldehydes20
Addition of the enantiomeric allyltrichlorostannane (R)-
3 to aldehyde (S)-4 led to a 67:34 mixture favoring the
1,4-syn-1,3-anti product 18 (Scheme 6). It is interesting
to point out that as the facial bias of the aldehyde is
to give the 1,3-anti product, we expected a matched case
and higher levels of diastereoselectivity in the reaction of
(R)-3 with (S)-4. We were surprized to see that was not
the case.
Entry
Aldehydes (R)
ds* 14a–e
Yield (%)
1
2
3
4
5
iPr
Ph
>95:5
>95:5
>95:5
85:15
84:16
82
89
88
89
90
2-Furyl
–CH@CHPh
–C(Me)@CH2
*ds=diastereoselectivity.
The stereoselectivity of these reactions can be explained
by chair-like six-membered ring transition states (B and
C) (Scheme 6). The relative stereochemistry for homoal-
lylic alcohols 16 and 18 was unambiguously established
on the basis of the 13C NMR analysis of their respective
acetonides 17 and 19 (Scheme 6).25,26 Treatment of 16
and 18 with TBAF at rt followed by treatment of the
corresponding diols under acidic conditions with 2,2-
dimethoxypropane gave acetonides 17 (99%) and 19
(88%), respectively. Observed 13C NMR resonances at
19.9, 30.4 and 98.4 for 17 are characteristic of a syn-
1,3-diol-acetonide and 13C NMR resonances at 25.2,
25.4 and 100.5 for 19 are consistent with an anti-1,3-
diol-acetonide.25
aldehyde approaches the complex from the side opposite
to the benzyl group at the oxygen (Scheme 4). A chair-
like arrangement is proposed, as it avoids steric interac-
tions between the aldehyde substituent and the axial
groups in the chair structure. The preference of the alkyl
group of the aldehyde to adopt an equatorial position
controls the aldehyde facial selectivity, resulting in the
favored 1,4-syn stereochemistry in the adduct.
The 1,4-syn relative stereochemistry for adducts 14a–e
was confirmed, after conversion of homoallylic alcohol
14b (R = Ph) to the corresponding 1,4-syn-diol 15, by
1
comparison of H- and 13C NMR data as well as its
optical rotation with literature values (Scheme 5).2c,22
Treatment of benzyl ether 14b with in situ prepared
lithium naphthalenide (5equiv) in THF at rt gave
the desired diol 15 in 89% yield (Scheme 5).
Allyltrichlorostannane (S)-3 reacted with aldehyde (S)-5
to give 1,2-anti-1,4-syn product 20 as the major product
(80:20 diastereoselectivity) (Scheme 7). The facial bias of
the chiral allyltrichlorostannane is dominated by the a-
methyl stereocenter and tends to give the 1,4-syn isomer
with Si-face attack. However, the facial bias of this alde-
hyde is to give the 1,2-syn product. This is another
example of a partially matched reaction.23
At this point we initiated a double stereodifferentiating
study.23 Allyltrichlorostannane (S)-3 reacted with alde-
hyde24 (S)-4 to give 1,3-syn-1,4-syn product 16 as the
major product (75:25 diastereoselectivity) (Scheme 6).
Allyltrichlorostannane (R)-3 was next employed in antic-
ipation that its preference for forming the 22 adduct,
combined with the same intrinsic preference of the sub-
strate, would lead to high selectivity. Indeed, this was
found to be the case. The reaction of chiral allyltrichloro-
stannane (R)-3 with aldehyde (S)-5 gives homoallylic
alcohol 22 (all-syn product) as the major isomer (Felkin
addition, matched case) (Scheme 7). The stereoselectivity
of this latter reaction is consistent with a chair-like six-
member-ring transition state (D) (Scheme 7).
The facial bias of this chiral allyltrichlorostannane is
dominated by the a-methyl stereocenter and tends to
give the 1,4-syn isomer with Si-face attack, but the facial
bias of this particular aldehyde is to give the 1,3-anti
product. Apparently, this represents a Ôpartially matched
caseÕ of double stereodifferentiation.23,24
.
-
OH
Li+
OH
Me
We next examined the addition of allylstannanes 3 to
chiral syn- and anti-disubstituted a-methyl-b-alkoxy
aldehydes 6 and 7. Allyltrichlorostannane (S)-3 reacted
with aldehyde 6 to give a 88:12 ratio favoring the all-
syn isomer 24, in a matched case (Scheme 8).
Me
THF, 25oC, 89%
14b
OBn
15
OH
Scheme 5.

8838
L. C. Dias, L. J. Steil / Tetrahedron Letters 45 (2004) 8835–8841
Cl
Cl
Cl
19.9
Me Me
98.4
30.4
Sn
1. TBAF, THF
BnO
OH
OTBS
Me
O
O
99%
Me
(S)-3
Me
Me
85%
2. Me2C(OMe)2
p-TsOH, 99%
Me
16
17
OBn
OBn
diastereoselectivity
75:25
O
OTBS
Me
H
25.2
Me Me
100.5
25.4
(S)-4
1. TBAF, THF
OTBS
95%
OH
O
O
87%
Me
Cl
Me
Cl
Cl
Me 2. Me2C(OMe)2
p-TsOH, 88%
Me
Sn
18
19
OBn
OBn
BnO
diastereoselectivity
66:34
Me
(R)-3
OTBS
H
OTBS
H
H
H
H
O
Me
H
H
H
Me
O
16
18
Me
O
Me
H
Cl3Sn
O
SnCl3
H
Bn
(S)
Bn
(R)
C
B
Scheme 6.
Cl
Cl
Cl
Sn
Me Me
1. TBAF, THF
99%
BnO
OH
OTBS
O
O
Me
(S)-3
Me
Me
2. Me2C(OMe)2
p-TsOH, 99%
20
85%
21
OBn
Me
OBn
Me
O
OTBS
diastereoselectivity
80:20
H
(S)-5
Me
Me Me
1. TBAF, THF
OTBS
95%
OH
O
O
87%
Me
Cl
Cl
Sn
Me
Cl
2. Me2C(OMe)2
p-TsOH, 88%
22
23
OBn
Me
OBn
Me
BnO
diastereoselectivity
> 95:5
Me
OTBS
(R)-3
H
Me
H
H
H
O
22
Me
O
SnCl3
H
Bn
(R)
D
Scheme 7.
Under the same conditions described before, allyltri-
chlorostannane (R)-3 reacted with aldehyde 6 to give
isomer 26 with 83:17 diastereoselectivity (Scheme 8).
In this latter case, the a-methyl stereocenter in allyltri-
chlorostannane (propensity for 1,4-syn addition) exerts
a dominant influence on aldehyde facial selectivity, by

L. C. Dias, L. J. Steil / Tetrahedron Letters 45 (2004) 8835–8841
8839
30.1 19.8
Me Me
98.7
Cl
Cl
Cl
OH
OTBS
Me
Sn
Me
Me
1. TBAF, THF
O
O
BnO
Me
Me
24
OBn
Me
(S)-3
Me
O
88%
OTBS
2. Me2C(OMe)2
p-TsOH, 84%
25
OBn
Me
Me
diastereoselectivity
88:12
Me
H
24.8 25.7
Me Me
100.5
6
Me
Cl
Me
OH
OTBS
O
O
1. TBAF, THF
Me
86%
Me
Cl
Me
Me
Cl
Sn
2. Me2C(OMe)2
p-TsOH, 87%
26
OBn
Me
Me
27
OBn
Me
Me
BnO
diastereoselectivity
83:17
(R)-3
Me
OTBS
H
OTBS
H
Me
Me
iPr
H
H
H
H
O
iPr
O
26
Me
O
24
Me
H
Cl3Sn
O
SnCl3
H
Bn
Bn
(S)
(R)
F
E
Scheme 8.
overriding the intrinsic bias imposed by the a and b-ste-
reocenters in the aldehyde, to give the 1,2-syn-1,3-syn
product. Although matched and mismatched cases were
again observed, the selectivity in the matched case was
somewhat disappointing, given the high selectivity ob-
served in the reaction of aldehyde 6 with allyltrichloro-
stannane 8 (Scheme 3).
This reaction with 1,2-anti b-OTBS aldehydes is charac-
terized by poor levels of diastereoselectivity only when
an achiral allyltrichlorostannane is used.
As before, the relative stereochemistry for compounds
28 and 30 was determined by analysis of the 13C
NMR of the corresponding acetonides 29 and 31
(Scheme 9). 13C NMR resonances at 19.6, 30.2 and
97.5 for 29 are characteristic of a syn-1,3-diol-acetonide
and 13C NMR resonanceÕs at 24.8, 25.7, and 100.5,
observed for 31, are characteristic of an anti-1,3-diol-
acetonide.25,26
The stereochemical assignment of compounds 24 and
26 was determined by 13C NMR analysis of acetonides
25 and 27, respectively (Scheme 8). 13C NMR reso-
nances at 19.8, 30.1, and 98.7 for 25 are characteristic
of a syn-1,3-diol-acetonide and the 13C NMR resonances
at 24.8, 25.7, and 100.5, observed for 27, are consistent
with an anti-1,3-diol-acetonide.25,26
The examples presented in this work show that the levels
of p-facial selection are dependent on the absolute ste-
reochemistries of the aldehydes as well as of the allyltri-
chlorostannanes. The results from these experiments
suggest that the stereochemical relationships between
the a and b aldehyde substituents may confer either a
reinforcing (matched) or opposing (mismatched) facial
bias on the carbonyl moiety. In this complex scenario,
the chiral allyltrichlorostannane may adopt either a rein-
forcing or nonreinforcing relationship. One possible rea-
son for this result could be attributed to the involvement
of energetically similar chair and twist-boat pericyclic
transition states that lead to diastereomeric product for-
mation. Another possibility to consider in these reac-
tions is that nonbonded interactions between the
allyltrichlorostannane and aldehyde a substituents may
not be significant in pericyclic transition states leading
to either Felkin or anti-Felkin addition products.13 We
believe that this chemistry is truly significant in the con-
text of acyclic diastereoselection and will prove to be
The reaction of allyltrichlorostannane (S)-3 with alde-
hyde 7 gave homoallylic alcohol 28 as the major isomer
in >95:5 diastereoselectivity (1,4-syn-1,3-syn, anti-Felkin
addition) (Scheme 9).
The reaction of allyltrichlorostannane (R)-3 with alde-
hyde 7 gave homoallylic alcohol 30 as the major isomer
in >95:5 diastereoselectivity (1,4-syn-1,3-anti, Felkin
addition, partially matched case) (Scheme 9).
The results described in Scheme 9 can be rationalized
with dominant acyclic 1,4-asymmetric induction from
the chiral allyltrichlorostannane. These are examples
of partially matched reactions, with the chiral allyltri-
chlorostannanes (S)-3 and (R)-3 being responsible for
control of the observed diastereoselectivities, through
transition states analogous to G and H, respectively.

8840
L. C. Dias, L. J. Steil / Tetrahedron Letters 45 (2004) 8835–8841
30.2 19.6
Me Me
97.5
Cl
Cl
Cl
OH
OTBS
Me
Sn
Me
Me
1. TBAF, THF
O
O
BnO
Me
Me
28
OBn
Me
(S)-3
Me
O
85%
OTBS
2. Me2C(OMe)2
p-TsOH, 91%
29
OBn
Me
Me
diastereoselectivity
> 95:05
Me
H
24.8 25.7
Me Me
100.5
7
Me
Cl
Me
OH
OTBS
O
O
1. TBAF, THF
Me
87%
Me
Cl
Me
Me
Cl
Sn
2. Me2C(OMe)2
p-TsOH, 89%
30
OBn
Me
Me
31
OBn
Me
Me
BnO
diastereoselectivity
88:12
(R)-3
Me
OTBS
Me
OTBS
Me
H
H
iPr
O
H
iPr
H
H
O
H
30
Me
28
Me
H
SnCl3
O
Cl3Sn
O
H
Bn
Bn
(R)
(S)
H
G
Scheme 9.
Tetrahedron Lett. 2001, 42, 8373; (f) Kumar, P.; Thomas,
E. J.; Tray, D. R. J. Braz. Chem. Soc. 2001, 12, 623; (g)
Gruttadauria, M.; Thomas, E. J. J. Chem. Soc. Perkin
Trans. 1 1995, 1469; (h) Nishigaishi, Y.; Kuramoto, H.;
Takuwa, A. Tetrahedron Lett. 1995, 36, 3353.
3. Dias, L. C.; Giacomini, R. J. Braz. Chem. Soc. 1998, 9,
357.
useful in the synthesis of more complex molecules, like
polyacetate and polypropionate-derived natural
products.27,28
Acknowledgements
4. Dias, L. C.; Giacomini, R. Tetrahedron Lett. 1998, 39,
5343.
We are grateful to FAEP-UNICAMP, FAPESP (Fun-
`
dac¸a˜o de Amparo a Pesquisa do Estado de Sa˜o Paulo)
and CNPq (Conselho Nacional de Desenvolvimento
5. Dias, L. C.; Meira, P. R. R.; Ferreira, E. Org. Lett. 1999,
1, 1335.
6. Dias, L. C.; Meira, P. R. R. Synlett 2000, 37.
7. Dias, L. C.; Ferreira, E. Tetrahedron Lett. 2001, 42,
7159.
8. Dias, L. C.; Ferreira, A. A.; Diaz, G. Synlett 2002,
1845.
´
´
Cientıfico e Tecnologico) for financial support. We also
thank Professor Carol H. Collins for helpful suggestions
about English grammar and style.
9. Dias, L. C.; Diaz, G.; Ferreira, A. A.; Meira, P. R. R.;
Ferreira, E. Synthesis 2003, 603.
References and notes
10. Dias, L. C.; Giacomini, R.; Meira, P. R. R.; Ferreira, E.;
Ferreira, A. A.; Diaz, G.; dos Santos, D. R.; Steil, L. J.
Arkivoc 2003, 10, 240–261.
11. Dias, L. C.; dos Santos, D. R.; Steil, L. J. Tetrahedron
Lett. 2003, 44, 6861.
12. We have recently described a very efficient and synthet-
ically useful 1,4-anti-1,5-anti boron-mediated aldol reac-
tion of chiral a-methyl-b-alkoxy methyl ketone with
achiral aldehydes Dias, L. C.; Bau´, R. Z.; de Sousa, M.
A.; Zukerman-Schpector, J. Org. Lett. 2002, 4, 4325.
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24. Since the diastereoselectivity of the reactions of these
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their enantiomeric purity, crude aldehydes were used in all
of the studies described in the text.
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26. Having confirmed the relative (syn or anti) relationship
between allylstannane-derived stereogenic centers, the
absolute stereochemistry of the newly formed hydroxyl
substituent was determined by ascertaining its relationship
to the stereocenter originating from the aldehydes, which
are of known configuration.
20. (a) The ratios were determined by 1H and 13C NMR
spectroscopic analysis of the purified product mixture; (b)
The syn and anti-products could not be separated and
were characterized as mixtures. We have been able to
separate both syn and anti diols originating from most of
the homoallylic alcohols and they were characterized
individually; (c) All of the percentage values represent data
obtained from at least three individual trials.
21. The relative stereochemistry for compounds 9–12 has been
confirmed after conversion to the corresponding aceto-
nides. See Ref. 11.
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27. All new compounds were isolated as chromatographi-
cally pure materials and exhibited acceptable 1H NMR,
13C NMR, IR, MS, and HRMS spectral data.
28. General procedure for allyltrichlorostannane coupling reac-
tions: To a solution of 2.5mmol of allylsilane 2 in 7mL of
dry CH2Cl2 at À78ꢁC was added 2.5mmol of SnCl4. T he
resulting solution was stirred at À78ꢁC for 30min when
2.7mmol of aldehyde in 2mL of H2Cl2 was added. This
mixture was stirred at À78ꢁC for 1h and quenched by the
slow addition of 0.2mL of Et3N, followed by 10mL of
saturated NH4Cl solution. The layers were separated and
the aqueous layer was extracted with CH2Cl2 (2 · 5mL).
The combined organic layer was dried (MgSO4), filtered,
and concentrated in vacuo. Purification by flash chroma-
tography on silica gel (30% EtOAc/hexanes) gave the
corresponding homoallylic alcohols.
23. Masamune, S.; Choy, W.; Peterson, J. S.; Sita, L. R.
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