Synthesis of Chiral α,δ-Dioxygenated Allylic Stannanes as Reagents for Carbohydrate Synthesis and Homologation

Article abstract of DOI:10.1021/jo961671b

The oe-oxygenated allylic stannanes 4.4 and 4.5, prepared through addition of Bu3SnLi to γ-OTBS crotonaldehyde 4.3c followed by etherification of the adduct with TBS-C1 or MOM-C1, undergo transmetalation with InCls and in situ addition to aldehydes leading to mainly anti adducts 5.1 or 5.2, accompanied by varying amounts of syn diastereomers. Selectivities of >95:5 can be realized with the MOM reagent 4.5 and ynals 4.3d and 4.3e or cyclohexanecarboxaldehyde 4.3a. With enals 4.3b and 4.3c, 80:20 mixtures of anti and syn adducts are formed. The S enantiomer 10.1 of stannane 4.5 has also been prepared as a reagent for carbohydrate synthesis. Accordingly, addition to ct-ODPS acetaldehyde 10.2 in the presence of InCl₃ leads to the adduct 10.3 as an inseparable 90:10 mixture of anti and syn diastereomers. Dihydroxylation of the OTBS derivative 10.4 affords the potential altrose precursor 10.5 in 81% yield.

Full text of DOI:10.1021/jo961671b

8732
J . Org. Chem. 1996, 61, 8732-8738
Articles
Syn th esis of Ch ir a l r,δ-Dioxygen a ted Allylic Sta n n a n es a s
Rea gen ts for Ca r boh yd r a te Syn th esis a n d Hom ologa tion
J ames A. Marshall* and Albert W. Garofalo
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901
Received August 29, 1996X
The δ-oxygenated allylic stannanes 4.4 and 4.5, prepared through addition of Bu3SnLi to γ-OTBS
crotonaldehyde 4.3c followed by etherification of the adduct with TBS-Cl or MOM-Cl, undergo
transmetalation with InCl3 and in situ addition to aldehydes leading to mainly anti adducts 5.1 or
5.2, accompanied by varying amounts of syn diastereomers. Selectivities of >95:5 can be realized
with the MOM reagent 4.5 and ynals 4.3d and 4.3e or cyclohexanecarboxaldehyde 4.3a . With
enals 4.3b and 4.3c, 80:20 mixtures of anti and syn adducts are formed. The S enantiomer 10.1
of stannane 4.5 has also been prepared as a reagent for carbohydrate synthesis. Accordingly,
addition to R-ODPS acetaldehyde 10.2 in the presence of InCl3 leads to the adduct 10.3 as an
inseparable 90:10 mixture of anti and syn diastereomers. Dihydroxylation of the OTBS derivative
10.4 affords the potential altrose precursor 10.5 in 81% yield.
In recent years we have devised methodology for the
Such reagents have the advantage that all carbons are
utilized in the homologation process leading to the polyol
derivative 2.4. However, attempts to effect 1,3-isomer-
ization of the R- to the γ-isomer 2.3 with BF3‚OEt2 and
other Lewis acids were unsuccessful owing to a facile
elimination leading to 1,3-dienes 2.2 or decomposition of
the stannane.4
synthesis of carbohydrates by a homologation strategy
that employs chiral γ-oxygenated allylic stannanes and
more recently, indium reagents (eq 1).1-3
We decided to explore the potential of transmetalation
with the milder Lewis acid, InCl3 as a possible route to
The approach lends itself to the preparation of any
given isomer of a differentially protected carbohydrate
target by relatively modest changes in Lewis acid,
stannane chirality, and aldehyde substrate. Our recent
synthesis of precursors to the eight diastereomeric hex-
oses in both the D and L series illustrates the efficiency
of the approach.3 The use of a common precursor
stannane 1.2 to access both anti- and syn-1,2-diol deriva-
tives 1.4 and 1.5 is of particular interest.
(4) Thomas has prepared â-oxygenated allylic trichlorostannanes
(e.g., ii) in situ through treatment of δ-oxygenated allylic tributylstan-
nanes i with SnCl4. These intermediates were found to react with
aldehydes through a chelated bicyclic transition state to afford mono-
protected 1,5-diols iii. Evidently, 1,2-elimination (as in 2.3 f 2.2) is
less favorable in this case, possibly owing to chelation between the
SnCl3 and adjacent OR substituents as in ii. Our attempts at
transmetalation of R-oxygenated allylic stannanes with SnCl4 or TiCl4
led to rapid decomposition, even at -78 °C.1
In related studies, we have been examining chiral R,δ-
dioxygenated stannanes, such as 2.1, for possible ap-
plications along lines similar to those of stannane 1.2.
X Abstract published in Advance ACS Abstracts, November 15, 1996.
(1) Marshall, J . A. Chem. Rev. 1996, 96, 31.
(2) Marshall, J . A.; Hinkle, K. W. J . Org. Chem. 1995, 60, 1920.
(3) Marshall, J . A.; Hinkle, K. W. J . Org. Chem. 1996, 61, 105.
S0022-3263(96)01671-4 CCC: $12.00 © 1996 American Chemical Society

Chiral R,δ-Dioxygenated Allylic Stannanes
J . Org. Chem., Vol. 61, No. 25, 1996 8733
a γ-indium intermediate such as 3.1, which, by virtue of
chelation, might be less inclined than the fugative tin
analogue 2.3 to undergo â-elimination. The expected
product of aldehyde homologation would be the anti
adduct 3.3 (eq 3).
Additions to crotonaldehyde (4.3b) and the γ-silyloxy-
crotonaldehyde (4.3c) were distinctly less selective. The
latter actually showed a slight preference for the syn
adduct, syn-5.1c. The R-OMOM reagent 4.5, on the other
hand, favored the anti adduct, anti-5.2c, by 80:20 with
aldehyde 4.3c. A higher anti diastereoselectivity of the
MOM vs the TBS reagent was also noted with the
alkynals 4.3d and 4.3e. Surprisingly, the overall anti
preference was greater in additions to the ynals than with
the related enals. In general, the R-OMOM reagent 4.5
proved superior to the R-OTBS analogue 4.4 for the
production of anti adducts. At this point it appeared that
the decreased anti:syn ratios were a function of both the
δ-OTBS and the R-OR1 substituent of stannanes 4.4 and
4.5. Interestingly the γ-subsituent of the enal or ynal
also influenced the selectivity (compare 5.1b with 5.1c
and 5.1d with 5.1e).
Two R,δ-dioxygenated allylic stannanes, 4.4 and 4.5,
were prepared for these studies starting from (Z)-2-
butene-1,4-diol (4.1), as outlined in eq 4. Monosilylation
To evaluate the influence of the R-OR1 substituent, we
carried out additions of the indium reagent derived from
R-OTBS crotylstannane 6.1 and the R-OMOM analogue
6.22 to representative aldehydes. The results of these
studies are presented in eq 6. In all cases, the reagent
was easily effected,5 and the resulting intermediate allylic
alcohol was oxidized with attendant Z f E isomerization
by PCC.6 Our exploratory studies were conducted with
racemic stannanes secured through addition of Bu3SnLi
to enal 4.3c, followed by addition of MOM-Cl or TBS-Cl,
respectively, to afford the R-oxygenated allylic stannane
product 4.4 or 4.5.1
Transmetalation of these stannane reagents with InCl3
was carried out at -78 to 0 °C in the presence of various
representative aldehydes. The results, summarized in
eq 5, revealed several interesting trends. Reaction of the
derived from the R-MOM stannane 6.2 gave higher anti:
syn product ratios compared to the TBS counterpart 6.1
with a given aldehyde. The differences are particularly
striking for heptanal (95:5 vs 75:25), (E)-2-butenal (94:6
vs 80:20), the δ-OTBS butenal (91:9 vs 70:30), and
2-nonynal (90:10 vs 77:23). By comparison, the γ-OTBS
allylic stannane 1.3 (R1 ) TBS)shows higher diastereo-
selectivity than the OMOM (R1 ) MOM) reagent in BF3-
promoted additions, where the favored products are syn-
6.3 and -6.4.7 Furthermore, enals give the highest syn:
anti product ratios in those additions.
The relative stereochemistry of the major adducts 5.1
and 5.2 may be assigned by analogy with the findings
summarized in eq 6 for the crotyl analogues. Additional
support for the cyclohexyl adduct, anti-5.1a , was secured
as shown in eq 7. Thus, the bis(TBS) ether 7.1, derived
from the known adduct syn-6.3b of cyclohexanecarbal-
dehyde and stannane 8.1 (BF3),7 was converted to alde-
hyde syn-7.2 by ozonolysis. Analogous treatment of the
bis(TBS) ether 7.3, derived from the adduct anti-5.1a ,
afforded the diastereomeric aldehyde anti-7.2
The stereochemistry of adduct anti-5.2b was confirmed
through comparison of the derived TBS ether, anti-8.2,
with the analogous ether, syn-8.2, prepared from syn-
6.3d , as outlined in eq 8.7
Adduct anti-5.1d was converted, via the bis TBS ether
9.1, to the aldehyde anti-9.3 through dihydroxylation
branched aldehyde, cyclohexanecarbaldehyde (4.3a ), with
the bis(silyloxy) reagent 4.4 proceeded in near-quantita-
tive yield with excellent anti:syn diastereoselectivity.
(5) McDougal, P. M.; Rico, J . G.; Oh, Y. I.; Condon, B. D. J . Org.
Chem. 1986, 51, 3388.
(6) Corey, E. J .; Suggs, J . W. Tetrahedron Lett. 1975, 2647.
(7) Marshall, J . A.; Welmaker, G. S. J . Org. Chem. 1992, 57, 7158.

8734 J . Org. Chem., Vol. 61, No. 25, 1996
Marshall and Garofalo
F igu r e 1. Chairlike transition states leading to syn and anti-
1,2-diol derivatives.
Ta ble 1. Ch em ica l Sh ift Com p a r ison s for th e OH P r oton
of Ad d u cts
with OsO4 and oxidative cleavage with H5IO6. The
diastereomeric aldehyde, syn-9.3, was secured in a like
manner from the adduct, syn-6.2c, prepared from stan-
nane 8.1 and 2-nonynal with BF3‚OEt2 (eq 9).8
δOH
R1
R2
R3
adduct
syn
anti
OTBS TBS
OTBS TBS
OTBS TBS
OTBS TBS
OTBS MOM c-C6H11
OTBS MOM (E)-MeCHdCH
OTBS MOM (E)-TBSOCH2CHdCH
(E)-MeCHdCH
(E)-TBSOCH2CHdCH
n-C6H13CtC
5.1b
5.1c
5.1d
5.1e
5.2a
5.2b
5.2c
6.3a
6.3b
6.3e
6.4c
6.4d
2.55 2.22
2.56 2.21
2.55 2.29
2.37 2.13
2.37 2.09
2.67 2.40
2.67 2.42
2.39 2.35
2.70 2.57
2.55 2.33
2.53 2.23
2.58 2.29
TBSOCH2CtC
H
H
H
H
H
TBS
TBS
TBS
n-C6H13
c-C6H11
n-C6H13CtC
MOM (E)-MeCHdCH
MOM (E)-TBSOCH2CHdCH
between the enol ether substituent R2 and the aldehyde
substituent R1 in the presumed chairlike transition state
A leading to the anti product (Figure 1). The effect would
be greater for OTBS than for OMOM. In transition state
C, leading to the syn adducts, this interaction is dimin-
ished. However, in C larger R1 groups such as cyclohexyl
may experience unfavorable steric opposition by ligands
on the indium. The relative importance of these opposing
effects will vary with the extent of bonding in the
transition state. The interactions depicted in A would
be less important in an early transition state as might
be expected for a more reactive aldehyde.
Additional support for the syn/ anti assignments of the
foregoing adducts came from the relative chemical shifts
of the OH proton as shown in Table 1. In all cases, this
proton was deshielded in the syn isomer in comparison
to the anti as a consequence of more effective internal
hydrogen bonding. A similar trend was previously noted
by Landmann and Hoffmann.9
The differing selectivities exhibited by the MOM and
TBS indium reagents may result from interactions
An alternative rationale for the enhanced anti:syn
product ratios from alkynals and cyclohexanecarboxal-
dehyde as opposed to the enals, depicted in eq 5, is also
based on relative reactivities. It is known that allylin-
dium species derived from allylic bromides and indium
(8) Marshall, J . A.; J ablonowski, J . A.; Elliott, L. M. J . Org. Chem.
1995, 60, 2662.
(9) Landmann, B.; Hoffman, R. W. Chem. Ber. 1987, 120, 331.

Chiral R,δ-Dioxygenated Allylic Stannanes
J . Org. Chem., Vol. 61, No. 25, 1996 8735
metal undergo facile E/ Z isomerization.10 Assuming E/ Z
interconversion also takes place with the oxygenated
analogues,11 the relative transition state energies for the
additions of the E vs Z (B vs D in Figure 1) reagents
may differ for the various aldehydes, with B being
significantly lower for alkynal and cyclohexyl aldehydes
and less so with the alkenyl aldehydes. In actuality, both
pathways may be operative with the anti adducts being
formed via A and the syn via D.12
Ta ble 2. Com p etition Exp er im en ts Betw een Ald eh yd es
4.3e vs 4.3c a n d 4.3a vs 4.3c for Sta n n a n e 4.5a
To estimate the relative reactivities of representative
aldehydes with the R-OMOM, δ-OTBS allylic stannane
4.5 in the InCl3-promoted additions, we carried out
competition experiments. Accordingly, the two compet-
ing aldehydes, the allylic stannane 4.5, and InCl3 were
mixed in the ratio 1:1:1:1 under the standard conditions.
After complete consumption of stannane, the reaction was
quenched and the products were isolated, along with any
unreacted aldehyde(s). The results, summarized in Table
2, clearly show that 4.3a and the acetylenic aldehyde 4.3e
are more reactive that the conjugated aldehyde 4.3c.
These findings are qualitatively consistent with the above
transition state analysis.
R1
product(s)
ratio
c-C6H11 (4.3e)
TBSOCH2CtC (4.3e)
5.3a /5.3c
5.3e/5.3c
80:20
100:0
a
Equimolar quantities of the stannane and each of the two
aldehydes were subjected to the standard reaction conditions. The
less reactive aldehyde was recovered.
The foregoing experiments serve to establish the
feasibility of utilizing R,δ-dioxygenated crotylstannanes
for the synthesis of anti monoprotected 1,2-diol adducts
from aldehydes. To complete this phase of our investiga-
tion, we elected to apply the methodology to a potential
precursor of the rare hexose D-(+)-altrose (eq 10).13 The
S enantiomer 10.1 of the R-OMOM, δ-OTBS crotylstan-
nane reagent of >95% ee was prepared by our standard
procedure involving reduction of the acylstannane with
(R)-BINAL-H followed by treatment of the resulting S
alcohol with MOM-Cl and (i-Pr)2NEt.14 Addition to
R-ODPS acetaldehyde 10.2 afforded the adduct 10.3 as
a 90:10 mixture of anti and syn diastereomers. The TBS
derivative 10.4 was separated from the syn isomer and
dihydroxylated with OsO4-NMO15 to afford diol 10.5. This
intermediate has the stereochemistry of D-(+)-altrose.
An independent synthesis of the TBS ether 10.6
derived from diol 10.5 was carried out as outlined in eq
11 with our established R- and γ-oxygenated crotylstan-
(10) Isaac, M. B.; Chan, T.-H. Tetrahedron Lett. 1995, 36, 8957.
(11) It is assumed that the intial transmetalation (i f ii) takes place
by an anti SE2′ process and the subsequent isomerization (ii f iii)
occurs with syn stereochemistry. Cf.: Marshall, J . A.; Yu, R. H.;
Perkins, J . F. J . Org. Chem. 1995, 60, 5550. The indium intermediates
are most likely unsymmetrical Cl-bridged dimers but are depicted as
monomers to simplify the analysis.
(12) A reviewer has suggested that syn adducts may arise via a
noncyclic transition state in which InCl3 is coordinated to the aldehyde
carbonyl. Because of their increased basicity, enals would be more
likely to follow this pathway. A similar explanation has been advanced
to account for the formation of anti aldol adducts from the reaction of
â-SPh enals and aromatic aldehydes with the Bu2BOTf-derived boron
enolate of a chiral N-propionyloxazolidinone: Danda, H.; Hansen, M.
M.; Heathcock, C. H. J . Org. Chem. 1990, 55, 173. This point will be
addressed in a future study with allylic indium intermediates in which
E/ Z isomerism is not an issue.
(13) This hexose is listed at $799.50/g in the 1996 Aldrich Catalog
(Aldrich No. 86,226-6): Aldrich Catalog Handbook of Fine Chemicals;
Aldrich Chemical Co.: Milwaukee, WI.
(14) Marshall, J . A.; Welmaker, G. S.; Gung, B. W. J . Am. Chem.
Soc. 1991, 113, 647.
nane reagents 11.1 and 11.5.1 Thus, InCl3-mediated
addition of the (S)-R-OMOM stannane 11.1 to aldehyde
10.2 afforded the anti adduct 11.2. Protection as the TBS
ether and ozonolysis yielded the aldehyde 11.4, which
was homologated with the (S)-γ-silyloxy allylic stannane
11.5 by the syn-selective BF3 protocol.1 This addition was
performed several times, but in each case, the adduct
11.6 was formed in relatively low yield. The TBS
derivative 11.7 was converted to aldehyde 11.8 by ozo-
(15) VanRheenen, V.; Kelly, R. C.; Cha, D. Y. Tetrahedron Lett. 1976,
1973.

8736 J . Org. Chem., Vol. 61, No. 25, 1996
Marshall and Garofalo
11H), 0.06 (s, 6H), 0.02 (s, 3H), 0.01 (s, 3H). Anal. Calcd for
C28H62O2Si2Sn: C, 55.53; H, 10.32. Found: C, 55.80; H, 10.41.
(E )-4-[(t er t -B u t y ld im e t h y ls ily l)o x y ]-1-(m e t h o x y -
m eth oxy)-1-(tr i-n -bu tylsta n n yl)-2-bu ten e (4.5). The pro-
cedure described for 4.4 was employed with 3.0 mL (17 mmol)
of diisopropylamine in 80 mL of dry THF, 7.9 mL (20 mmol)
of 2.5 M n-BuLi in hexanes, 4.9 mL (18 mmol) of Bu3SnH, and
3.3 g (17 mmol) of 4.3c. The crude hydroxy stannane was
dissolved in 80 mL of dry CH2Cl2. The solution was stirred
at 0 °C, and 1.4 mL (18 mmol) of i-Pr2NEt followed by 3.2 mL
(18 mmol) of chloromethyl methyl ether was added. The
reaction was allowed to warm to rt and quenched after 16 h
with saturated aqueous NH4Cl. The mixture was extracted
with CH2Cl2. The organic extract was dried over MgSO4, and
the solvent was removed by distillation under reduced pres-
sure. Chromatography of the crude product on a silica gel
column with 1:9 EtOAc/hexanes as eluant afforded 5.0 g (56%)
of MOM ether 4.5: 1H NMR δ 5.80 (dd, J ) 15.4, 6.7 Hz, 1H),
5.50 (ddt, J ) 15.4, 5.0, 1.5 Hz, 1H), 4.66, 4,52 (ABq, J ) 6.2
Hz, 2H), 4.63 (m, 1H), 4.17 (d, J ) 5.0 Hz, 1H), 3.34 (s, 3H),
1.59-1.44 (m, 2H), 1.38-1.23 (m, 2H), 0.96-0.86 (m, 14H), 0.06
(s, 6H). Anal. Calcd for C24H52O3SiSn: C, 53.84; H, 9.79.
Found: C, 54.00; H, 9.72.
(E,r el-1R,2S)-2,5-[Bis(ter t-b u t yld im et h ylsilyl)oxy]-1-
cycloh exyl-3-p en ten -1-ol (a n ti-5.1a ). A solution of 0.07 g
(0.33 mmol) of indium(III) chloride in 9.0 mL of EtOAc was
stirred at rt as 0.04 mL (0.30 mmol) of 4.3a was added. The
solution was then cooled to -78 °C, and a solution of 0.18 g
(0.30 mmol) of allylstannane 4.4 in 0.5 mL of EtOAc was
added. The reaction mixture was allowed to slowly warm to
rt, quenched with saturated aqueous NaHCO3, and extracted
with Et2O. The organic extract was dried over MgSO4, and
the solvent was removed by distillation under reduced pres-
sure. Chromatography of the crude product on a silica gel
column with 1:9 EtOAc/hexanes as eluant afforded 0.07 g
(99%) of anti-5.1a : 1H NMR (CDCl3, 360 MHz) δ 5.76 (dd, J
) 15.4, 3.5 Hz, 1H), 5.71 (dd, J ) 15.4, 5.3 Hz, 1H), 4.19 (m,
3H), 3.28 (ddd, J ) 7.9, 4.0, 2.2 Hz, 1H), 2.36 (d, J ) 2.2 Hz,
1H), 1.72-0.94 (m, 14H), 0.90 (s, 9H), 0.89 (s, 9H), 0.06 (s,
9H), 0.04 (s, 3H). Anal. Calcd for C23H48O3Si2: C, 64.42; H,
11.28. Found: C, 64.31; H, 11.31.
(E,r el-1R,2S)-5-[(ter t-Bu tyld im eth ylsilyl)oxy]-1-cyclo-
h exyl-2-(m eth oxym eth oxy)-3-p en ten -1-ol (a n ti-5.2a ). The
procedure described for anti-5.1a was employed with 0.03 g
(0.14 mmol) of indium(III) chloride in 3.0 mL of EtOAc, 0.02
mL (0.13 mmol) of 4.3a and 0.08 g (0.14 mmol) of allylstannane
4.5. Chromatography of the crude product on a silica gel
column with 1:9 EtOAc/hexanes as eluant afforded 0.02 g
(99%) of anti-5.2a : 1H NMR δ 5.84 (dt, J ) 15.8, 4.6 Hz, 1H),
5.68 (dd, J ) 15.8, 8.1 Hz, 1H), 4.72, 4.55 (ABq, J ) 6.6 Hz,
2H), 4.22 (d, J ) 4.6 Hz, 2H), 4.14 (dd, J ) 8.1, 4.2 Hz, 1H),
3.45 (ddd, J ) 7.3, 4.2, 3.1 Hz, 1H), 3.36 (s, 3H), 2.09 (d, J )
3.1 Hz, 1H), 1.81-0.95 (m, 11H), 0.91 (s, 9H), 0.07 (s, 6H).
Anal. Calcd for C19H38O4Si: C, 63.64; H, 10.68. Found: C,
63.75; H, 10.72.
(E,r el-4S,5R)-4-[(ter t-Bu tyld im eth ylsilyl)oxy]-2-u n d e-
cen -5-ol (6.3a ). The procedure described for anti-5.1a was
followed with 0.11 g (0.51 mmol) of indium(III) chloride in 4.0
mL of EtOAc, 0.07 mL (0.47 mmol) of heptanal, and a solution
of 0.29 g (0.61 mmol) of crotylstannane 6.1 in 0.5 mL of EtOAc.
Chromatography of the crude product on a silica gel column
with 1:9 EtOAc/hexanes as eluant afforded 0.13 g (91%) of
adduct 6.3a as a 75:25 mixture of anti and syn diastereo-
mers: 1H NMR anti δ 5.67 (dq, J ) 15.4, 6.2 Hz, 1H), 5.50
(dd, J ) 15.4, 7.3 Hz, 1H), 4.00 (dd, J ) 7.3, 4.0 Hz, 1H), 3.56
(m, 1H), 2.57 (d, J ) 3.8 Hz, 1H), 1.76 (d, J ) 6.2 Hz, 3H),
1.52-1.32 (m, 13H), 0.94 (s, 9H), 0.10 (s, 3H), 0.08 (s, 3H).
(E,E,4R,5S)-5-(Meth oxym eth oxy)-2,6-octadien -4-ol (6.4c).
The procedure described for anti-5.1a was employed with 0.15
g (0.66 mmol) of indium(III) chloride in 9.0 mL of EtOAc, 0.05
mL (0.60 mmol) of 4.3b, and 0.32 g (0.79 mmol) of allylstan-
nane 6.2. Chromatography of the crude product on a silica
gel column with 1:9 EtOAc/hexanes as eluant afforded 0.10 g
nolysis, as before. Reduction and subsequent silylation
yielded the protected hexitol 10.6 identical to the previ-
ously prepared sample according to comparison of 13C and
1H NMR spectra.
To complete our intended synthesis of D-altrose, we
attempted to selectively cleave the primary OTBS ether
(R1) of intermediate 10.6. Unfortunately, we were unable
to effect this conversion under a variety of conditions
(TBAF; HOAc, THF, H2O; PPTS; HF; MeCN; to name a
few). In each case a mixture of polyols was produced.
Thus it would appear that a successful realization of this
goal will require a change in protecting group strategy.
Efforts along these lines and additional applications of
this methodology to rare carbohydrates will be the subject
of future studies.
Exp er im en ta l Section 16
(Z)-4-[(ter t-Bu tyld im eth ylsilyl)oxy]-2-bu ten -1-ol (4.2).
A solution of 20.4 g (239 mmol) of cis-2-butene-1,4-diol in 400
mL of dry THF was stirred at 0 °C as 96.0 mL (240 mmol) of
2.5 M n-BuLi in hexanes was slowly added.5 The mixture was
stirred for 1 h, and 36.1 g (240 mmol) of TBS-Cl was added.
The reaction mixture was allowed to slowly warm to room
temperature over 3 h, quenched with saturated aqueous
NH4Cl, and extracted with Et2O. The organic layer was dried
over MgSO4, and the solvent was removed by distillation under
reduced pressure. Bulb to bulb distillation of the crude product
(85 °C 1.0 mmHg)) afforded 46.1 g (95%) of alcohol 4.2: 1H
NMR δ 5.68 (m, 2H), 4.24 (d, J ) 4.9 Hz, 2H), 4.18 (t, J ) 5.6
Hz, 2H), 1.99 (t, J ) 5.9 Hz, 1H), 0.89 (s, 9H), 0.07 (s, 6H).
(E)-4-[(ter t-Bu tyld im eth ylsilyl)oxy]-2-bu ten a l (4.3c). A
solution of 18.6 g (91.9 mmol) of alcohol 4.2 in 200 mL of dry
CH2Cl2 was stirred at 0 °C as 19.2 g of powdered 4 Å sieves
followed by 20.3 g (94.0 mmol) of PCC was added.6 The
reaction mixture was allowed to slowly warm to room tem-
perature. After 16 h, the solvent was removed by distillation
under reduced pressure and the resulting brown solid was
triturated with ether and filtered through a plug of silica. The
filtrate was concentrated under reduced pressure. Bulb to bulb
distillation of the crude product (1.0 mm, 65 °C) afforded 13.2
g (71%) of aldehyde 4.3c: 1H NMR (CDCl3, 400 MHz) δ 9.58
(d, J ) 8.1 Hz, 1H), 6.87 (dt, J ) 15.4, 3.3 Hz, 1H), 6.38 (ddt,
J ) 15.4, 8.1, 2.2 Hz, 1H), 4.43 (dd, J ) 3.2, 2.2 Hz, 2H), 0.90
(s, 9H), 0.07 (s, 6H).
(E)-1,4-[Bis(ter t-bu tyld im eth ylsilyl)oxy]-1-tr i-n -bu tyl-
sta n n yl-2-bu ten e (4.4). A solution of 0.45 mL (3.2 mmol) of
diisopropylamine in 12 mL of dry THF was stirred at 0 °C as
1.2 mL (3.0 mmol) of 2.5 M n-BuLi in hexanes was added. The
solution was stirred for 15 min and then 0.73 mL (2.7 mmol)
of Bu3SnH was added. The resulting solution was stirred for
15 min and then cooled to -78 °C. To this mixture was added
0.50 g (2.5 mmol) of 4.3c. The reaction mixture was stirred
for 45 min, quenched with saturated aqueous NH4Cl, and
extracted with Et2O. The organic layer was dried over MgSO4,
and the solvent was removed by distillation under reduced
pressure. The crude hydroxy stannane was dissolved in 12
mL of dry CH2Cl2. The solution was stirred at rt and 0.20 g
(3.0 mmol) of imidazole followed by 0.38 g (2.5 mmol) of
chlorotrimethylsilane was added. After 2 h, the reaction was
quenched with saturated aqueous NH4Cl and extracted with
CH2Cl2. The organic extract was dried over MgSO4, and the
solvent was removed by distillation under reduced pressure.
Chromatography of the crude product on a silica gel column
with 1:49 EtOAc/hexanes as eluant afforded 0.68 g (45%) of
silyl ether 4.4: 1H NMR δ 5.85 (dd, J ) 15.0, 4.8 Hz, 1H),
5.47 (ddt, J ) 15.0, 5.5, 1.8 Hz, 1H), 4.68 (m, 1H), 4.16 (m,
1H), 1.59-1.40 (m, 2H), 1.35-1.23 (m, 2H), 0.92-0.85 (m,
(16) For typical experimental protocols, see: Marshall, J . A.; Wang,
X-j. J . Org. Chem. 1991, 56, 960. Unless otherwise stated, 1H and 13C
NMR spectra were determined at 300 and 75 MHz, respectively, as
dilute solutions in CDCl3.
(85%) of adduct 6.4c as an 94:6 mixture of anti and syn dia-
1
stereomers: [R]23 117.4 (c 1.0, CH2Cl2); H NMR anti δ 5.66
D
(m, 2H), 5.40 (dd, J ) 15.4, 7.0 Hz, 1H), 5.30 (dd, J ) 15.4,

Chiral R,δ-Dioxygenated Allylic Stannanes
J . Org. Chem., Vol. 61, No. 25, 1996 8737
8.1 Hz, 1H), 4.63, 4.48 (ABq, J ) 6.6 Hz, 2H), 3.99 (m, 1H),
3.88 (dd, J ) 8.1, 4.0 Hz, 1H), 3.28 (s, 3H), 2.23 (br, 1H), 1.65
(d, J ) 6.6, Hz, 3H), 1.63 (d, J ) 6.6 Hz, 3H). Anal. Calcd for
C10H18O3: C, 64.49; H, 9.74. Found: C, 64.29; H, 9.69.
(E,r el-1S,2R)-1,2-[Bis(ter t-b u t yld im et h ylsilyl)oxy]-1-
cycloh exyl-3-p r op en e (7.1). A solution of 0.27 g (0.92 mmol)
of alcohol syn-6.3b in 10 mL of dry CH2Cl2 was stirred at 0 °C
as 0.16 mL (1.4 mmol) of 2,6-lutidine followed by 0.25 mL of
tert-butyldimethysilyl trifluoromethanesulfonate was added.
After 40 min, the reaction was quenched with saturated
aqueous NH4Cl and extracted with CH2Cl2. The organic
extract was dried over MgSO4, and the solvent was removed
by distillation under reduced pressure. Chromatography of
the crude product on a silica gel column with hexanes as eluant
afforded 0.36 g (95%) of TBS ether 7.1: 1H NMR δ 5.58 (m,
2H), 4.09 (m, 1H), 3.28 (m, 1H), 1.81-0.94 (m, 14H), 0.90 (s,
9H), 0.89 (s, 9H), 0.05 (s, 6H), 0.03 (s, 3H), 0.01 (s, 3H).
(r el-2R,3S)-2,3-[Bis(ter t-bu tyld im eth ylsilyl)oxy]-3-cy-
cloh exylp r op a n a l (syn -7.2). A solution of 0.15 g (0.37 mmol)
of unsaturated diether 7.1 in 8.0 mL of dry CH2Cl2 was stirred
at -78 °C as ozone was bubbled through the solution. After
4 min the solution acquired the blue characteristic of ozone,
and 0.10 mL of dimethyl sulfide was added. The solution was
allowed to warm to rt and stirred for 40 min. The solvent was
removed by distillation under reduced pressure. Chromatog-
raphy of the crude product on a silica gel column with 1:9
EtOAc/hexanes as eluant afforded 0.13 g (86%) of aldehyde
syn-7.2: 1H NMR δ 9.83 (s, 1H), 4.07 (d, J ) 5.0 Hz, 1H), 3.67
(dd (apparent t), J ) 5.0 Hz, 1H), 1.73-1.62 (m, 6H), 1.23-
0.88 (m, 5H), 0.92 (s, 9H), 0.91 (s, 9H), 0.09 (s, 3H), 0.08 (s,
3H), 0.07 (s, 3H), 0.04 (s, 3H). Anal. Calcd for C21H44O3Si2:
C, 62.94; H, 11.07. Found: C, 61.62; H, 11.00.
(r el-2R,3R)-2,3-[Bis(ter t-bu tyld im eth ylsilyl)oxy]p r op a -
n a l (a n ti-7.2). The ozonolysis procedure described for alde-
hyde syn-7.2 was employed with 0.11 g (0.20 mmol) of
unsaturated diether 7.3 in 8.0 mL of dry CH2Cl2. Chroma-
tography of the crude product on a silica gel column with 1:9
EtOAc/hexanes as eluant afforded 0.07 g (84%) of aldehyde
anti-7.2: 1H NMR δ 9.60 (d, J ) 1.5 Hz, 1H), 4.03 (dd, J )
2.7, 1.5 Hz, 1H), 3.62 (dd, J ) 6.9, 2.7 Hz, 1H), 1.89-1.54 (m,
6H), 1.26-1.08 (m, 5H), 0.92 (s, 9H), 0.88 (s, 9H), 0.08 (br,
9H), 0.06 (s, 3H).
(E,r el-1R,2S)-1,2,5-[Tr is(ter t-Bu tyld im eth ylsilyl)oxy]-
1-cycloh exyl-3-p en ten e (7.3). A solution of 0.19 g (0.44
mmol) of alcohol anti-5.1a in 2.0 mL of dry CH2Cl2 was stirred
at rt as 0.08 mL (0.64 mmol) of 2,6-lutidine followed by 0.12
mL (0.52 mmol) of tert-butyldimethysilyl trifluoromethane-
sulfonate was added. After 30 min, the reaction was quenched
with saturated aqueous NH4Cl and extracted with CH2Cl2. The
organic extract was dried over MgSO4, and the solvent was
removed by distillation under reduced pressure. Chromatog-
raphy of the crude product on a silica gel column with 1:49
EtOAc/hexanes as eluant afforded 0.22 g (92%) of TBS ether
7.3: 1H NMR δ 5.69 (dd, J ) 15.4, 6.6 Hz, 1H), 5.60 (dt, J )
15.4, 4.0 Hz, 1H), 4.15 (d, J ) 4.0 Hz, 2H), 4.10 (dd, J ) 6.6,
4.4 Hz, 1H), 3.34 (dd (apparent t), J ) 4.4 Hz, 1H), 1.83-1.44
(m, 6H), 1.27-0.97 (m, 5H), 0.90 (s, 9H), 0.88 (s, 9H), 0.87 (s,
9H), 0.06 (s, 6H), 0.05 (s, 3H), 0.04 (s, 3H), 0.03 (s, 3H), 0.02
(s, 3H).
2.6 g (0.68 mmol) of alcohol syn-6.3b in 7.0 mL of dry CH2Cl2
was stirred at 0 °C as 0.12 mL (0.69 mmol) of N,N-diisopro-
pylethylamine was added followed by 0.06 mL (0.72 mmol) of
chloromethyl methyl ether. The reaction was allowed to warm
to rt. After 16 h, TLC analysis still showed the presence of
unreacted alcohol. An additional 0.12 mL (0.69 mmol) of N,N-
diisopropylethylamine and 0.06 mL (0.72 mmol) chloromethyl
methyl ether were added. After 24 h the reaction was
quenched with saturated aqueous NH4Cl and extracted with
CH2Cl2. The organic extract was dried over MgSO4, and the
solvent was removed by distillation under reduced pressure.
Chromatography of the crude product on a silica gel column
with 1:9 EtOAc/hexanes as eluant afforded 0.24 g (81%) of
adduct syn-8.2 and 0.02 g (6%) of unreacted alcohol, syn-6.3b:
1H NMR δ 5.76 (dt, J ) 15.4, 4.4 Hz, 1H), 5.60 (m, 2H), 5.46
(dd, J ) 15.4, 6.6 Hz, 1H), 4.69, 4.62 (ABq, J ) 6.6 Hz, 2H),
4.18 (d, J ) 4.4 Hz, 2H), 4.11 (dd (apparent t), J ) 5.9 Hz,
1H), 3.97 (dd (apparent t), J ) 5.9 Hz, 1H), 3.36 (s, 3H), 1.68
(d, J ) 6.2 Hz, 3H), 0.90 (s, 9H), 0.88 (s, 9H), 0.06 (s, 9H),
0.03 (s, 3H). Anal. Calcd for C22H46O4Si2: C, 61.34; H, 10.76.
Found: C, 61.12; H, 10.68.
2-[(ter t-Bu tyld ip h en ylsilyl)oxy]eth a n a l (10.2). A sus-
pension of 0.56 g (23 mmol) of sodium hydride in 200 mL of
dry THF was stirred at 0 °C as 1.2 g (20 mmol) of ethylene
glycol was slowly added. The reaction mixture was allowed
to warm to rt. After 40 min, 6.2 g (23 mmol) of tert-
butylchlorodiphenylsilane was added. After 16 h, the reaction
was quenched with saturated aqueous NH4Cl and extracted
with ether. The organic extract was dried over MgSO4
, and
the solvent was removed by distillation under reduced pres-
sure. Bulb to bulb distillation of the crude product (129 °C
(0.5 mmHg)) afforded 5.6 g (94%) of 2-[(tert-butyldiphenyl-
silyl)oxy]-1-ethanol: 1H NMR (CDCl3, 300 MHz) δ 7.68 (m,
4H), 7.41 (m, 6H), 3.77 (m, 2H), 3.69 (m, 2H), 2.12 (m, 1H).
A solution of 1.8 mL (21 mmol) of oxalyl chloride in 70 mL
of dry CH2Cl2 was stirred at -78 °C as 3.0 mL (42 mmol) of
dimethyl sulfoxide followed by a solution of 5.6 g (19 mmol) of
the above prepared alcohol in 10 mL of CH2Cl2 was added.
After 15 min, 13 mL of triethylamine was added and the
reaction mixture was allowed to warm to rt. The solvent was
then removed by distillation under reduced pressure to afford
a white solid. The solid was triturated with 250 mL of 1:4
EtOAc/hexanes and filtered through a plug of silica gel.
Solvent was removed from the filtrate by distillation under
reduced pressure. Bulb to bulb distillation of the crude product
(120 °C (0.6 mmHg)) afforded 5.0 g (89%) of aldehyde 10.2:
1H NMR (CDCl3, 300 MHz) δ 9.73 (m, 1H), 7.66 (m, 4H), 7.41
(m, 6H), 4.22 (m, 2H), 1.10 (s, 9H).
(E,2R,3S)-6-[(ter t-Bu tyld im eth ylsilyl)oxy]-1-[(ter t-bu -
t yld ip h en ylsilyl)oxy]-3-(m et h oxym et h oxy)-4-h exen -2-
ol (10.3). The procedure described for anti-5.1a was employed
with 0.23 g (1.1 mmol) of indium(III) chloride in 8.0 mL of
EtOAc, 0.29 g (1.0 mmol) of aldehyde 10.2 in 1.0 mL of EtOAc,
and 0.29 g (0.54 mmol) of (S)-allylstannane 10.1 in 1.0 mL of
EtOAc. Chromatography of the crude product on a silica gel
column with 1:4 EtOAc/hexanes as eluant afforded 0.43 g
(82%) of alcohol 10.3 as a 10:1 mixture of anti and syn dia-
1
stereomers: [R]23
43.5 (c 0.8, CH2Cl2); H NMR (CDCl3, 300
D
MHz) δ 7.66 (m, 4H), 7.39 (m, 6H), 5.81 (dt, J ) 15.4, 4.4 Hz,
1H), 5.63 (dd, J ) 15.4, 7.7 Hz, 1H), 4.68, 4.53 (ABq, J ) 6.6
Hz, 2H), 4.17 (d, J ) 4.4 Hz, 2H), 4.15 (m, 1H), 3.85-3.67 (m,
3H), 3.28 (s, 3H), 2.47 (d, J ) 4.0 Hz, 1H), 1.07 (s, 9H), 0.89
(s, 9H), 0.04 (s, 6H). Anal. Calcd for C30H48O5Si2: C, 66.13;
H, 8.88. Found: C, 66.39; H, 8.95.
(E, E,r el-4S,5R)-1,5-[Bis(ter t-bu tyld im eth ylsilyl)oxy]-
4-(m eth oxym eth oxy)-2,6-octa d ien e (a n ti-8.2). The proce-
dure described for 7.1 was employed with 0.14 g (0.31 mmol)
of alcohol anti-5.2b in 5.0 mL of dry CH2Cl2, 0.06 mL (0.50
mmol) of 2,6-lutidine and 0.12 mL (0.50 mmol) of tert-
butyldimethylsilyl trifluoromethanesulfonate. Chromatogra-
phy of the crude product on a silica gel column with 1:9 EtOAc/
hexanes as eluant afforded 0.13 g (65%) of silyl ether anti-
8.2: 1H NMR δ 5.75 (dt, J ) 15.4, 4.4 Hz, 1H), 5.65-5.44 (m,
3H), 4.68, 4.56 (ABq, J ) 6.6 Hz, 2H), 4.18 (d, J ) 4.4 Hz,
2H), 4.03 (dd (apparent t), J ) 5.7 Hz, 1H), 3.94 (dd, J ) 7.7,
5.1 Hz, 1H), 3.34 (s, 3H), 1.69 (d, J ) 6.2 Hz, 3H), 0.90 (s,
9H), 0.87 (s, 9H), 0.06 (s, 6H), 0.03 (s, 3H), 0.01 (s, 3H). Anal.
Calcd for C22H46O4Si2: C, 61.34; H, 10.76. Found: C, 61.51;
H, 10.69.
(E,4S,5R)-1,5-[Bis(ter t-bu tyld im eth ylsilyl)oxy]-6-[(ter t-
b u t yld ip h en ylsilyl)oxy]-4-(m et h oxym et h oxy)-4-h exen e
(10.4). The procedure described for 7.1 was employed with
0.43 g (0.79 mmol) of alcohol 10.3 in 8.0 mL of dry CH2Cl2,
0.14 mL (1.2 mmol) of 2,6-lutidine, and 0.24 mL (1.0 mmol) of
tert-butyldimethysilyl trifluoromethanesulfonate. Chroma-
tography of the crude product on a silica gel column with 1:9
EtOAc/hexanes as eluant afforded 0.43 g (83%) of adduct
10.4: [R]23 32.9 (c 0.4, CH2Cl2); 1H NMR δ 7.56 (m, 4H), 7.30
D
(m, 6H), 5.64 (dt, J ) 15.4, 4.0 Hz, 1H), 5.55 (dd, J ) 15.4, 8.1
Hz, 1H), 4.59, 4.42 (ABq, J ) 6.6 Hz, 2H), 4.17 (dd, J ) 8.1,
2.9 Hz, 1H), 4.07 (m, 2H), 3.77 (ddd (apparent dt), J ) 6.2, 2.9
(E,E,r el-4S,5S)-1,5-[Bis(ter t-bu tyld im eth ylsilyl)oxy]-4-
(m eth oxym eth oxy)-2,6-octa d ien e (syn -8.2). A solution of

8738 J . Org. Chem., Vol. 61, No. 25, 1996
Marshall and Garofalo
Hz, H2), 3.45 (m, 2H), 3.22 (s, 3H), 0.96 (s, 9H), 0.80 (s, 9H),
0.73 (s, 9H), -0.05 (s, 6H), -0.07 (s, 3H), -0.15 (s, 3H). Anal.
Calcd for C36H62O5Si3: C, 65.60; H, 9.48. Found: C, 65.54; H,
9.52.
-0.07 (s, 3H), -0.08 (s, 3H), -0.09 (s, 3H); 13C NMR δ 135.82
(2C), 135.79 (2C), 133.58, 133.51, 129.52, 129.34, 127.59 (2C),
127.43 (2C), 97.38, 80.54, 74.72, 73.88, 72.32, 64.97, 63.89,
55.97, 29.71, 27.05 (3C), 26.07 (6C), 25.92 (3C), 25.89 (3C),
19.02, 18.44, 18.18, 18.12, -3.57, -3.87, -4.06, -4.29, -4.88,
-4.92, -5.29, -5.40. Anal. Calcd for C48H92O7Si5: C, 62.55;
H, 10.06. Found: C, 62.44; H, 9.96.
B. F r om Alcoh ol 11.9. The procedure described for 7.1
was employed with 0.03 g (0.04 mmol) of alcohol 11.9 in 3.0
mL of dry CH2Cl2, 0.01 mL (0.09 mmol) of 2,6-lutidine, and
0.01 mL (0.05 mmol) of tert-butyldimethysilyl trifluoromethane-
sulfonate. Chromatography of the crude product on a silica
gel column with 1:9 EtOAc/hexanes as eluant afforded 0.02 g
(69%) of silyl ether 10.5 identified by comparison of the 1H
NMR spectrum with that of the material prepared above in
part A. The [R]D of this sample and that derived from part A
was nearly zero and varied [(1] from run to run.
(2R,3R,4R,5R)-1,5-[Bis(ter t-bu tyld im eth ylsilyl)oxy]-6-
[(ter t-bu tyld ip h en ylsilyl)oxy]-4-(m eth oxym eth oxy)-2,3-
h exa n ed iol (10.5). A solution of 0.07 g (0.10 mmol) of
unsaturated ether 10.4 in 5.0 mL of acetone and 0.5 mL of
water was stirred at rt as 0.04 g (0.32 mmol) of N-methylmor-
pholine N-oxide was added followed by 0.21 mL (0.02 mmol)
of a 2.5 wt % solution of OsO4 in isobutyl alcohol. After 22 h,
the reaction was quenched with cold, saturated aqueous
NaHSO3 and stirred for 1 h. The mixture was then extracted
with EtOAc. The organic extract was dried over MgSO4, and
the solvent was removed by distillation under reduced pres-
sure. Chromatography of the crude product on a silica gel
column with 1:9 EtOAc/hexanes afforded 0.06 g (81%) of diol
10.5: [R]23 -14.9 (c 3.4, CH2Cl2); 1H NMR δ 7.61 (m, 4H),
D
7.31 (m, 6H), 4.69, 4.59 (ABq, J ) 5.9 Hz, 2H), 4.07 (m, 1H),
3.85-3.61 (m, 6H), 3.52 (dd, J ) 10.3, 5.5 Hz, 1H), 3.30 (s,
3H), 3.00 (br, 1H), 2.70 (br, 1H), 0.97 (s, 9H), 0.82 (s, 9H), 0.76
(s, 9H), -0.01 (s, 6H), -0.04 (s, 3H), -0.13 (s, 3H). Anal. Calcd
for C36H64O7Si3: C, 62.38; H, 9.31. Found: C, 62.53; H, 9.37.
(2R,3R,4R,5R) 2,4,5,6-[t et r a k is(ter t-Bu t yld im et h ylsi-
lyl)oxy]-1-[(t er t -b u t yld ip h e n ylsilyl)oxy]-3-(m e t h oxy-
m eth oxy)h exa n e (10.6). A. F r om Diol 10.5. The proce-
dure described for 7.1 was employed with 0.05 g (0.06 mmol)
of diol 10.5 in 1.0 mL of dry CH2Cl2, 0.03 mL (0.21 mmol) of
2,6-lutidine, and 0.04 mL (0.16 mmol) of tert-butyldimethysilyl
trifluoromethanesulfonate. Chromatography of the crude
product on a silica gel column with 1:9 EtOAc/hexanes as
eluant afforded 0.06 g (97%) of silyl ether 10.6: 1H NMR δ
7.65 (m, 4H), 7.29 (m, 6H), 4.71, 4.59 (ABq, J ) 5.9 Hz, 2H),
4.16 (dd, J ) 7.3, 2.9 Hz, 1H), 3.75-3.41 (m, 7H), 3.19 (s, 3H),
0.96 (s, 9H), 0.85 (s, 9H), 0.78 (s, 18H), 0.75 (s, 9H), 0.06 (s,
3H), 0.04 (s, 3H), -0.03 (s, 3H), -0.04 (s, 3H), -0.05 (s, 3H),
Ack n ow led gm en t. Support for this work was pro-
vided by a research grant (R01-AI31422) from the
National Institutes of Allergy and Infectious Diseases.
We thank Michelle Elliott for a sample of aldehyde syn-
9.3.
Su p p or tin g In for m a tion Ava ila ble: Experimental pro-
cedures for 5.1b-e, 5.2b, 5.2c, 5.2e, 6.3b-e, 6.4d , 9.1, anti-
1
9.3, 10.1, 11.2-11.4, and 11.6-11.9 and H NMR spectra for
4.2, 4.3c, 5.1c, 5.1d , 6.3a , 6.3b, 6.4c, 6.4d , 7.1, anti-7.2, 7.3,
9.1 anti-9.3, 10.1, 10.1 (R)-mandelate, 10.1 (S)-mandelate,
10.2, 10.3, 10.3 (R)-mandelate, 10.3 (S)-mandelate, 10.6, and
11.6-11.9 (37 pages). This material is contained in libraries
on microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
J O961671B