Copyright
Reprinted from the Journal of the American Chemical Society, 1991, II3.
O 1991 by the American Chemical Society and reprinted by permission of the copyright
Carbon{arbon Bond Formationin AqueousEthanol:
Transformationof Unprotected
Diastereoselective
Carbohydrates
to Higher CarbonSugarsUsing Allyl
Bromideand Tin Metsll
WaltherSchmid2and GeorgeM. Whitesides*
Departmentof Chemistry,Haruard Uniuersity
02I 38
Cambridge,Massachusetts
ReceiuedApril 5, I99l
additionof allyl groups
This reportdescribes
the *nucleophilic"
in aqueto the carbonylmoietiesof unprotected
carbohydrates
ous/organicsolvents(eq l). Thesereactionsare basedon proCH2OH
cI|0
I
I
(c8og)
cH2oH
CArOB
II
(CIiOH) n-r
Sn,
n
lllyl
azo/tr.LoB,
bronide
ultrrsound
tl
H-C-OR
I
Ho-9-s
tl
9H,
tl
CH:Cl{z
(CaOE)
"-1
o'
BO-{-B
|
8--f -oE
(1)
$xt
CE:C[2
ceduresdevelopedand applied to non-sugaraldehydesand ketones
by Luche,s{ Nokami,T Benezra,8and otherse'I0using reactionof
allylic halideswith zinc or tin metal in the presenc€of the carbonyl
acceptor. When applied to carbohydrates,the reactions proceed
with useful diastereoselectivity
and permit the synthetic utilization
of these water-solublesubstratesdirectly in aqueoussolutions
without protection. The adducts were convertedto higher carbon
aldoses by ozonolysis of the deprotected polyols followed by
suitablederivatization.
The yields reportedin Table I were obtainedin ethanol/water
mixtures. Using tetrahydofuraninsteadof ethanoldid not improve
the yield but did slow the rate. Commercially availabletin powder
(Alfa company; 100 mesh) was used,and the suspensionof the
reactantswas sonicatedfor 12-18 h in an ultrasoniccleaning bath
(Cole-Parmer8852)." Although the pH drops sharply during
*pH' =
I ), we
the courseof the reaction (typically to a value of
pH
positive
control. The polyols
did not run the reaction under
generatedwere acetylated to simplify the purification procedure.
(l) This work was supportedby the NIH, Grant GM 30367.
(2) Erwin SchrodingerPostdoctoralFellow of the Fondszur F6rderungder
wissenschaftlichen
Forschungin Osterreich(Austrian ScienceFoundation).
(3) Einhorn,C.; Einhorn,J.; Luche, J. L. Synthesi.r19t9, 787-813.
(4) Luche,C. J.; Damiano,J. C. J. Am. Chem.Soc.19t0, 102,7926-'7927.
(5) Petrier,C.; Luche, J. L. J. Org. Chem.19t5, J0, 912-915.
(6) Petrier, C.; Einhorn, J,; Luche, J. L. Tetrahedron Lctt. 1985, 26,
t449-t452.
(7) Nokami, J.; Otera, J.; Sudo, T.; Okawara,R. Organometallics19t3,
2. t9t-t93.
(8) Mattes, H.; Benezra,C. TetrahedronLett. lgtl, 26,5697-5698.
(9) Wilson,S. R.;Guazzaroni,M. E. J. Org. Chem.19t9,54,3087-3091.
(10) Wu, S.; Huang, B.; Gao, X. Synth. Commun. 1990' 20(9),
t279-t286.
(l l) Ultrasoundincreasesthe reactivityof many metals: Suslik, K. S.;
Casadonte,J. D.;Doktycz, S. J. Chem.Mater.l9t9, 1, 6-8. Ultrasound: Its
Chemical, Physical and Biological Effects; Suslik, K. S., Ed.; VCH PubJ. C.; Petrier,C.; Luche,J. L.
lishers;New York, 1988. de Souza-Barboza,
J. Org. Chem.1988,J3, 1212-1218.
0002-7863
l9ll15l3-6674$02.5010@ l99l AmericanChemicalSociety
owner.
6675
Table L NucleophilicAddition of Allyl Groupsto Aldoses
startlng
carbohydrate
producto
yield,6
Vo
diastereomericratio.
(threo:erythro)
D-erythrose
I
52
4.0:l
o-ribose
2
65
3.5:l
o-arabinose
3
85
5.5:l
o-glucose
4
70
6.5:l
D-mannose
5
90
6.0:l
2-deoxy-o-glucosed
26
I.5:l
2-NAc-o-glucose
0
2-NAc-o-mannose
0
aReactions
werecarriedout in 9:l ethanol/waterwith 2 equiveach
of tin powder(100 mesh)and allyl bromideand promotedby ultrasonicationuntil completion(12-16 h). 6Basedon isolatedperacetyrated
cDeterminedfrom NMR. dDiastereomers
diastereomers.
not separated.
SchemeI. Conversions
of o-Ribose,o-Arabinose,
and n-Glucose
to
Heptoseand OctoseDerivatives
6, 7, and 8
"vo
I
-o"
ro"
roH
Los
D-Ribo!a
Aco---1
Aco--i
Acol
SD,
Aco
o""'
The yields reported in Table I were of isolated materials, following
column chromatography over silica gel. Experimental details are
given in supplementarymaterial.
To assignthe stereochemistryof the chiral center formed by
addition of the allyl groups,we transformedthree of the adducts
(2,3. and 4) to the correspondingheptoseand octosederivatives
6, 7, and 8 by ozonolysisand appropriatederivatization(Scheme
I). In the pyranoseforms of thesehigher carbon sugars,the
stereochemistryof the newly generatedcenter could be assigned
easilyby analysisof couplingconstantsin the 'H NMR spectra.
For the major diastereomerformed in each reaction,the hydroxy
function formed and that originally presentat C-2 of the starting
aldosehavea threo relationship. This result is in agreementwith
observationsmade by Coxon et al.l2 for this type of reactionon
aldehydescontainingan asymmetriccenteradjacentto the carbonyl function. The diastereoselectivity
is lower in the one case
in which there is no hydroxy group presentat C-2. For aldoses
having N-acetyl groups in position 2, no reaction was observed
under the reactionconditionsused,l3
This tin-promotedC{ bond forming reactionextendsthe range
of synthetic methods applicable to unprotectedsugarsin protlc
solventsand should be especiallyuseful in preparing higher carbon
sugars. We are applying these methodsto more highly functionalizedsystemsand to other halide sources.
,
Y
I
Ho--l
.oH
Fo"
L-olr
AcO---1
o"o---]
AcO l
| )-o
(_J>-ocH3
I
o"O
,
D-Ara.binoae
E_O
Y
l
T_ VT
"o--]
.oH
f-oH
Los
D-GIucose
AcO
- tT- v.
NJ--l
Aco l--o
l--olc
Loo"
SupplementaryMaterial Available: Experimental details for
the preparationof l-8 (7 pages). Ordering information is given
on any current mastheadpage.
(12) Coxon,J. M.;van Eyk, S. J.;Steel,P. J. Tetahedronlztt.19135.26.
6t2t-6124.
(13) This observationmay suggesta possiblecomplexationof the presumptiveallyltin spcciesto the a-hydroxy function.