- Email: [email protected]
The reaction of derivatives of methyl 2,3-O-benzylidene-α-l -rhamnopyranoside with butyl-lithium
Carbohydrate Research, IO0 (1952) clO-ci3 Elsevier Scientific Publishing Company, Amsterdam - Printed in The Netherlands
Preliminary Tbe
communication
reaction
of derivatives
of methyl
2,10-benzylidene-lr-L-rhamnopyranoside
with
but+lithium
J~HS S. BRI~IXCO~IBE, RODERICK HASXA, MAY Chemisrr~ Deparfnrent,
Drtndee Universit?,
S.SXED, AND LESLIEC.N. TUCKER
Dmdee
DDI 4HN (Great Britain)
(Received July Ilth, 1981; accepted for publication, July 3Oth, 19Sl)
Retrosynthetic ana!ysis of a number of rare sugars currently of interest in our laboratory indicated that methyl 2,6-dideoxy-z-L-erythro-hexopyranosid-3-ulose bearing a te_mporary protecting-group at position 4 \vould serve as a common precursor_ Literature precedents’*’ su ggested that such a compound might be derived from a suitably protected methyl 2,3-O-benzylidene-;c-r-rhamnopyranoside by expulsion of benzaldehyde through the action of organolithium compounds (formally as shown in 1).The diastereoisomeric methyl 2,3-U-benzylidene-4-O-methyI-x-rrhamnopyranosides (2), for example, react’.’ with butyl-lithium in tetrahydrofuran at -30’ to give an acceptable yield of 3, which has been transformed3 into L-evernitrose (a) by way of cyanomesylation. However, Horton and co-workers’ have demonstrated that neither the hydroxylated compound 5 nor the benzyl ether 6 is suitable for the reaction, because either formation of the 4-oxyanion or abstraction of a proton from the benzyl group impedes the removal of a proton from the dioxoIane rir.g. Although the transformation 748 (40 “/dyield) has been accomplished’ with see-butyl-lithium protecting
in tetrahydrofuran
group introduces
at -3O”,
the use of tetrahydropyran-Z-y1
a new centre of asymmetry,
as a
which is general!y undesirable.
Our own efforts to secure a temporarily protected methyl 2,6-dideoxy-r-LerJrlzro-hexopyranosid-3-u1ose have focused on the reaction of butyl-lithium with 9 and 10 at low temperatares. Each of the derivatives 9 and 10 was obtained as a distillable mixture of diastereoisomers when 5’ was ailowed to react overnight at room temperature with either 2-methoxyethoxymethyl chloride’ or methoxymethyt chloride in dichloromethane containing ethyldi-isopro.p$amine. The acetal groups at O-4 of 9 and 10 should Gthstand the strongly basic conditions of the elimination reaction, furnishing products having an acid-labile group at this position*. Butyl-lithium reacted with 9 in tetrahydrofuran at -40” to give, after chromatography, the ketone 11 (m-p. 42-&l”, [cz]~ -235” (c 1, chloroform)) in 41 o/0yield,
*Although cleavage of 2-methoxyethoxymethyl ethers occurs on prolonged treatment with butyilithium at room temperature, this reaction does not appear to be preeminent at lower temperatures6. The cleavage of ethers by alkyl-lithium reagents is well known’. ocO.%6215~82@X&OOOO /S 02.75, @ 1982 -
Elsevier Scientific Publishing Company
PRELIhUNARY
cl1
CO,MIfUNICATION
OMe
OMe
OMe
..gid
RoM$ *oY+f
NC2
-I--” Ph
Ph
1
2
R
4
Me
=
5RZk’
13l?=
=
R
=
Me
R
=
THP
R
=
621
11 R
=
MEM
7
R
=
tetrOnydTO~yrQn-2-yl(r~?)
I2R
=
C+O.Me
9
R =
IO F! =
l!iR
3
8
6
CH,OCH,CH,OMe
Meo~oH
(MEM)
cu*ot-re
H
14R
Me
,6
R
=
H
=
we
17
and with IO at -30” to afford I2 (m-p. 73-74.5”, [z],, -344” (c 1, chloroform)j in 38 “//oyield. The somewhat moderate yields of 11 and 12, which are comparable to those obtained in similar reactions2’1, are recompensed by the directness of the route. The usefulness of II and 12 in synthesis is illustrated by the followinS examples. r-Digitoxose (14) is available by reduction of 11 with sodium borohydride to give 13 (SlOA, b-p. 95-100” (bath)/02 mm&, @]n - I2S” (c 1, chloroform)), which yielded the free sugar (71 ?A, m-p. 105-107”, b]n - 47” (equil., c 1, water)**) on hydrolysis with boilinS, aqueous acetic acid. Methylation’ of 13 in anhydrous tetrahydrofuran Save 15 {92x, b.p. 75-50” (bath}i0.05 mmHg, [zcJD - 158’ (c I, chloroform)J, (16) on acidic hydrolysis (0.05~ sulphuric acid at which liberated L-cymarose*** 65-70” for 2 h). HydroSeenation of the oxime IS3 ?A, m-p. 78-81 O, [c],, -320” (c I, chloroform)) derived from 11 over Adams’ catalyst in methanol containing acetic anhydride furnished the acztamido derivative 17 {b-p. 125-132 0 (bath)/0.1 in virtually quantitative yield. Hydrolysis mmHg, [z]n - 166” (c 1.3, chloroform)) of 17 with boiling, aqueous acetic acid gave N-acetyl-L-ristosamine {72x, m-p. 133135”, [z]n -38” (equil., c 0.7, water)+). This synthesis of an L-ristosamine derivative compares favourably with others in the literature’3. In connection with synthetic work on methyl-branched amino and nitro sugars, we !lave found that 12 can be converted by the Bourgeois procedure’4 into the cyano**n-Digitoxose has m.p. 105-105”, [c& +~7.8” (equil., c 1.06, water)*. ***This sugar, which was required in connection with structural studies of variosel”, was identified by comparison with the D enantiomerll. ?The D enantiomer has m-p. 133”, I& f39”
(equil., c 0.5, water)“.
Cl2
PRELIMINARY
OMe
2’ =
ou.FY=
CN
19
2’ =
CN.R-=
OH
20 R’ =
O.MS.d
=
21 R- =
CN.R-
=
CN
0M.Z
OMLZ
HO 18
COMhlXJNICATION
22 R’ =
Me.R-=
23 R* =
NHAc.R-
Me0 NHAC =
Me
OMs
hydrins 18 {m-p_ 74.576.5”, [a],, - 146” (c 0.85, chloroform)) [z]n -31’ (c 1, c hi oroform)). Equilibration studies established product, whose configuration at C-3 was assigned by analogy3 tion”. Mesylation of 18 and 19 gave 20 {m-p. 112-l la”, [z],, form)) and 21 {m-p. 127-128.5” (_dec.), [z]o - 155” (c 1.15,
or 19 (m-p. 84.586”, that 18 is the kinetic and chemical correla- 126” (c 0.6, chlorochloroform)), respec-
tively, in good yield. Current work, based on literature precedents3*‘“*‘6, is directed towards the synthesis of the r-vancosaminide 22”, its stereoisomer 23l*, and Lrubranitrose’9 (24) [a stereoisomer of i_-evernitrose” (4)] from 20 and 21. Since these transformations involve manipulation of the configuration at C-4, they require temporary protection of the hydroxyl group at this position*. This approach to Lrubranitrose (24). for example, was prescribed by the failure of the benzylidcne-Ltalopyranoside 25 to eliminate benzaldehyde on treatment with butyl-lithium” (cf- 2-+32). New compounds had elemental analyses and spectroscopic properties in agreement with the structures assigned. ACICNOWLEDGMEXT
We thank
the Iraqi Government
for financial
support
(to M.S.S.).
REFERENCES A. KLEMER XXD G. RODEMEYER, C’hem. Ber., 107 (1974) 2612-2614. D. M. CLODF., D. HORTON, AND W. WECKERLE, Ckzrbohy&_ Res., 19 C-1976)305-314. J. Yos~rar.u~h M. MATXZAW~. K--I. SATO, AXO Y. NAGASAWA. Cmbohydr. Res., 76 (1979) 67-78. A. KLEUER XXD D. Bxucxu, J_ Chem. Res_ (S), (1978) 30X E. J. COREY, J.-L. GR.XS, ASD P. UWCH, Tetrahedron Lett., (1976) 809-812. R. J. AX?~ERSON, K. G. ADAMS, H. R. CX+ZX, AND C. A. Hocarcrc, J_ Org. Chem., 45 (1980) 2229~2236_ See, for example, H. GILMAN, A. H. HAUBEIN, AND H. I%RTZFELD, J_ Org. C’hem., 19 (1954) 1034-IOU); P. TOMEUIU~US, D. AMIC~. S. BEXRE, K. DIJMZ~E,D. HART, R. HITES, A. METZGER, k\D R. NOW& ibid.,38 (1973) 322-%; R. A. ELLIsoS. R. GRIFFIN, AND F. N. KOTXMS, J. Orgammet. C’hem., 36 (1972) 209-213_ T. K. CHELFG, D. HORTON, ASD W. WECKERLE, Carboh_vd-_Rex, 58 (1977) 139-151, and references
therein.
*We have recently reported” an alternative synthesis of the r_-vancosaminide 22, in which an oxidation-reduction sequence was used to invert the configuration at C-4 of the equatorial isomer.
PRELIBIINAXY
CO;M~fUNICATiON
cl3
9 J. S. BRIXXO~E, B. D. JONES, M. STACEY, AND J. J. WILLARD, Carbohydr. Rex, 2 (1966) 167-169. 10 J. S. B~~~~ACOMBE, Z. AL--AN, AND A. S. MENGECH, J. Chem. Sot., Perkin Trans. I, (1980) 1800-1803. 11 D. A. PRIXS, Nelrp. Chim. Acfa, 29 (1946) 3X-382. 12 D. HORTON AND W. WECKERLE, Carbohydr. Res., 46 (1976) 227-235. 13 F. S~~ARICSUI, I_ PELYV~, R. BOCN.~ ASD G. BUT.& Tetrahedron Lerr., (1975) 111l-l 114; W. W. LEE, H. Y. WV, J. J. MARSH, JR., C. W. MOSHER, E. M. ANTON, L. GOODSIAN, AND D. W. HENRY, J_ Med. Chem., 18 (1975) 767-768; F. ARCAMONE, A. BARGIO~, G. CASSINELLI, S. PENCO, XND S. HANESSIAN, Carbohydr. Res., 46 (1976) c3-c5; G. FRONU, C. FUGANTI, AND P. GRASSELLI, Titrahedrorz L&t., (1980) 2999-3!XlO; K. HE~NS, M. LI,M, AND J. I. PARK, ibid., (1976) 1477-1480; I. PELYV&, F. S~TARICSUI, ~&m R. BOGN.&R, Carhohydr. Rex, 76 (1979) 257-260; K. HEYNS, J. FELDLIANN, D. HADA~ICZYK, J. SCHXVENIXER, AND J. THIEVE,Chem. Ber., 114 (1981) 232-239. 14 J.-M. BOURGEOE, Heir. Chim. AC&, 57 (1974) 2553-2557; 59 (1976) 2114-2124. 15 J. S. BRI~UCOXIBE AND R. HANNA, unpublished results. 16 J. YOSHIMURA, M. MATSU~LVA, AND M. FUNABXN, Ball. Chem. Sot. Jpn., 51 (1978) 2064-2067; T. THXT TH,XNG, F. WINTER=, A. OLESKER, A. LAGRASGE, AND G. L~ACS, Chem. Commun., (1979) 153-154. 17 W. D. WERIKGX, D. H. Wr~r~xm, J. FEENEY, J. P. BROLVN, AND R. W. KING, f_ C/mm Sot., Perkin Trans. I, (1972) 443146; A. W. JOHXSON, R. M. Sum, AXD R. D. GUTHRIE, ibid., (1972) X53-2159. 18 M_ DEBOXO AND R. M. MOLLOY, J. Org. Chem., 45 (1980) 468-687. 19 S. A. MI~SAK, H. HOEKS~IA, AND L. ht. PSCHIGODA, J. Anribiot., 32 (1979) 771-772. 20 A. K. GANGULY, 0. Z. SARRE, AND H. REIBMNX, J. Am. Chem. Sot., 90 (1968) 7129-7130; A. K. GAXGULY, 0. Z. SARRE, A. T. MCPHZJL, AND K. D. ONAN, Chem. Commw~., (1977) 313-314. 21 H. I. AH&MD, J. S. BRNXOMBE, A. S. MENGECH, AND L. C. N. TUCKER, Carbohydr. Res., 93 (1981) 288-293.
Preliminary Tbe
communication
reaction
of derivatives
of methyl
2,10-benzylidene-lr-L-rhamnopyranoside
with
but+lithium
J~HS S. BRI~IXCO~IBE, RODERICK HASXA, MAY Chemisrr~ Deparfnrent,
Drtndee Universit?,
S.SXED, AND LESLIEC.N. TUCKER
Dmdee
DDI 4HN (Great Britain)
(Received July Ilth, 1981; accepted for publication, July 3Oth, 19Sl)
Retrosynthetic ana!ysis of a number of rare sugars currently of interest in our laboratory indicated that methyl 2,6-dideoxy-z-L-erythro-hexopyranosid-3-ulose bearing a te_mporary protecting-group at position 4 \vould serve as a common precursor_ Literature precedents’*’ su ggested that such a compound might be derived from a suitably protected methyl 2,3-O-benzylidene-;c-r-rhamnopyranoside by expulsion of benzaldehyde through the action of organolithium compounds (formally as shown in 1).The diastereoisomeric methyl 2,3-U-benzylidene-4-O-methyI-x-rrhamnopyranosides (2), for example, react’.’ with butyl-lithium in tetrahydrofuran at -30’ to give an acceptable yield of 3, which has been transformed3 into L-evernitrose (a) by way of cyanomesylation. However, Horton and co-workers’ have demonstrated that neither the hydroxylated compound 5 nor the benzyl ether 6 is suitable for the reaction, because either formation of the 4-oxyanion or abstraction of a proton from the benzyl group impedes the removal of a proton from the dioxoIane rir.g. Although the transformation 748 (40 “/dyield) has been accomplished’ with see-butyl-lithium protecting
in tetrahydrofuran
group introduces
at -3O”,
the use of tetrahydropyran-Z-y1
a new centre of asymmetry,
as a
which is general!y undesirable.
Our own efforts to secure a temporarily protected methyl 2,6-dideoxy-r-LerJrlzro-hexopyranosid-3-u1ose have focused on the reaction of butyl-lithium with 9 and 10 at low temperatares. Each of the derivatives 9 and 10 was obtained as a distillable mixture of diastereoisomers when 5’ was ailowed to react overnight at room temperature with either 2-methoxyethoxymethyl chloride’ or methoxymethyt chloride in dichloromethane containing ethyldi-isopro.p$amine. The acetal groups at O-4 of 9 and 10 should Gthstand the strongly basic conditions of the elimination reaction, furnishing products having an acid-labile group at this position*. Butyl-lithium reacted with 9 in tetrahydrofuran at -40” to give, after chromatography, the ketone 11 (m-p. 42-&l”, [cz]~ -235” (c 1, chloroform)) in 41 o/0yield,
*Although cleavage of 2-methoxyethoxymethyl ethers occurs on prolonged treatment with butyilithium at room temperature, this reaction does not appear to be preeminent at lower temperatures6. The cleavage of ethers by alkyl-lithium reagents is well known’. ocO.%6215~82@X&OOOO /S 02.75, @ 1982 -
Elsevier Scientific Publishing Company
PRELIhUNARY
cl1
CO,MIfUNICATION
OMe
OMe
OMe
..gid
RoM$ *oY+f
NC2
-I--” Ph
Ph
1
2
R
4
Me
=
5RZk’
13l?=
=
R
=
Me
R
=
THP
R
=
621
11 R
=
MEM
7
R
=
tetrOnydTO~yrQn-2-yl(r~?)
I2R
=
C+O.Me
9
R =
IO F! =
l!iR
3
8
6
CH,OCH,CH,OMe
Meo~oH
(MEM)
cu*ot-re
H
14R
Me
,6
R
=
H
=
we
17
and with IO at -30” to afford I2 (m-p. 73-74.5”, [z],, -344” (c 1, chloroform)j in 38 “//oyield. The somewhat moderate yields of 11 and 12, which are comparable to those obtained in similar reactions2’1, are recompensed by the directness of the route. The usefulness of II and 12 in synthesis is illustrated by the followinS examples. r-Digitoxose (14) is available by reduction of 11 with sodium borohydride to give 13 (SlOA, b-p. 95-100” (bath)/02 mm&, @]n - I2S” (c 1, chloroform)), which yielded the free sugar (71 ?A, m-p. 105-107”, b]n - 47” (equil., c 1, water)**) on hydrolysis with boilinS, aqueous acetic acid. Methylation’ of 13 in anhydrous tetrahydrofuran Save 15 {92x, b.p. 75-50” (bath}i0.05 mmHg, [zcJD - 158’ (c I, chloroform)J, (16) on acidic hydrolysis (0.05~ sulphuric acid at which liberated L-cymarose*** 65-70” for 2 h). HydroSeenation of the oxime IS3 ?A, m-p. 78-81 O, [c],, -320” (c I, chloroform)) derived from 11 over Adams’ catalyst in methanol containing acetic anhydride furnished the acztamido derivative 17 {b-p. 125-132 0 (bath)/0.1 in virtually quantitative yield. Hydrolysis mmHg, [z]n - 166” (c 1.3, chloroform)) of 17 with boiling, aqueous acetic acid gave N-acetyl-L-ristosamine {72x, m-p. 133135”, [z]n -38” (equil., c 0.7, water)+). This synthesis of an L-ristosamine derivative compares favourably with others in the literature’3. In connection with synthetic work on methyl-branched amino and nitro sugars, we !lave found that 12 can be converted by the Bourgeois procedure’4 into the cyano**n-Digitoxose has m.p. 105-105”, [c& +~7.8” (equil., c 1.06, water)*. ***This sugar, which was required in connection with structural studies of variosel”, was identified by comparison with the D enantiomerll. ?The D enantiomer has m-p. 133”, I& f39”
(equil., c 0.5, water)“.
Cl2
PRELIMINARY
OMe
2’ =
ou.FY=
CN
19
2’ =
CN.R-=
OH
20 R’ =
O.MS.d
=
21 R- =
CN.R-
=
CN
0M.Z
OMLZ
HO 18
COMhlXJNICATION
22 R’ =
Me.R-=
23 R* =
NHAc.R-
Me0 NHAC =
Me
OMs
hydrins 18 {m-p_ 74.576.5”, [a],, - 146” (c 0.85, chloroform)) [z]n -31’ (c 1, c hi oroform)). Equilibration studies established product, whose configuration at C-3 was assigned by analogy3 tion”. Mesylation of 18 and 19 gave 20 {m-p. 112-l la”, [z],, form)) and 21 {m-p. 127-128.5” (_dec.), [z]o - 155” (c 1.15,
or 19 (m-p. 84.586”, that 18 is the kinetic and chemical correla- 126” (c 0.6, chlorochloroform)), respec-
tively, in good yield. Current work, based on literature precedents3*‘“*‘6, is directed towards the synthesis of the r-vancosaminide 22”, its stereoisomer 23l*, and Lrubranitrose’9 (24) [a stereoisomer of i_-evernitrose” (4)] from 20 and 21. Since these transformations involve manipulation of the configuration at C-4, they require temporary protection of the hydroxyl group at this position*. This approach to Lrubranitrose (24). for example, was prescribed by the failure of the benzylidcne-Ltalopyranoside 25 to eliminate benzaldehyde on treatment with butyl-lithium” (cf- 2-+32). New compounds had elemental analyses and spectroscopic properties in agreement with the structures assigned. ACICNOWLEDGMEXT
We thank
the Iraqi Government
for financial
support
(to M.S.S.).
REFERENCES A. KLEMER XXD G. RODEMEYER, C’hem. Ber., 107 (1974) 2612-2614. D. M. CLODF., D. HORTON, AND W. WECKERLE, Ckzrbohy&_ Res., 19 C-1976)305-314. J. Yos~rar.u~h M. MATXZAW~. K--I. SATO, AXO Y. NAGASAWA. Cmbohydr. Res., 76 (1979) 67-78. A. KLEUER XXD D. Bxucxu, J_ Chem. Res_ (S), (1978) 30X E. J. COREY, J.-L. GR.XS, ASD P. UWCH, Tetrahedron Lett., (1976) 809-812. R. J. AX?~ERSON, K. G. ADAMS, H. R. CX+ZX, AND C. A. Hocarcrc, J_ Org. Chem., 45 (1980) 2229~2236_ See, for example, H. GILMAN, A. H. HAUBEIN, AND H. I%RTZFELD, J_ Org. C’hem., 19 (1954) 1034-IOU); P. TOMEUIU~US, D. AMIC~. S. BEXRE, K. DIJMZ~E,D. HART, R. HITES, A. METZGER, k\D R. NOW& ibid.,38 (1973) 322-%; R. A. ELLIsoS. R. GRIFFIN, AND F. N. KOTXMS, J. Orgammet. C’hem., 36 (1972) 209-213_ T. K. CHELFG, D. HORTON, ASD W. WECKERLE, Carboh_vd-_Rex, 58 (1977) 139-151, and references
therein.
*We have recently reported” an alternative synthesis of the r_-vancosaminide 22, in which an oxidation-reduction sequence was used to invert the configuration at C-4 of the equatorial isomer.
PRELIBIINAXY
CO;M~fUNICATiON
cl3
9 J. S. BRIXXO~E, B. D. JONES, M. STACEY, AND J. J. WILLARD, Carbohydr. Rex, 2 (1966) 167-169. 10 J. S. B~~~~ACOMBE, Z. AL--AN, AND A. S. MENGECH, J. Chem. Sot., Perkin Trans. I, (1980) 1800-1803. 11 D. A. PRIXS, Nelrp. Chim. Acfa, 29 (1946) 3X-382. 12 D. HORTON AND W. WECKERLE, Carbohydr. Res., 46 (1976) 227-235. 13 F. S~~ARICSUI, I_ PELYV~, R. BOCN.~ ASD G. BUT.& Tetrahedron Lerr., (1975) 111l-l 114; W. W. LEE, H. Y. WV, J. J. MARSH, JR., C. W. MOSHER, E. M. ANTON, L. GOODSIAN, AND D. W. HENRY, J_ Med. Chem., 18 (1975) 767-768; F. ARCAMONE, A. BARGIO~, G. CASSINELLI, S. PENCO, XND S. HANESSIAN, Carbohydr. Res., 46 (1976) c3-c5; G. FRONU, C. FUGANTI, AND P. GRASSELLI, Titrahedrorz L&t., (1980) 2999-3!XlO; K. HE~NS, M. LI,M, AND J. I. PARK, ibid., (1976) 1477-1480; I. PELYV&, F. S~TARICSUI, ~&m R. BOGN.&R, Carhohydr. Rex, 76 (1979) 257-260; K. HEYNS, J. FELDLIANN, D. HADA~ICZYK, J. SCHXVENIXER, AND J. THIEVE,Chem. Ber., 114 (1981) 232-239. 14 J.-M. BOURGEOE, Heir. Chim. AC&, 57 (1974) 2553-2557; 59 (1976) 2114-2124. 15 J. S. BRI~UCOXIBE AND R. HANNA, unpublished results. 16 J. YOSHIMURA, M. MATSU~LVA, AND M. FUNABXN, Ball. Chem. Sot. Jpn., 51 (1978) 2064-2067; T. THXT TH,XNG, F. WINTER=, A. OLESKER, A. LAGRASGE, AND G. L~ACS, Chem. Commun., (1979) 153-154. 17 W. D. WERIKGX, D. H. Wr~r~xm, J. FEENEY, J. P. BROLVN, AND R. W. KING, f_ C/mm Sot., Perkin Trans. I, (1972) 443146; A. W. JOHXSON, R. M. Sum, AXD R. D. GUTHRIE, ibid., (1972) X53-2159. 18 M_ DEBOXO AND R. M. MOLLOY, J. Org. Chem., 45 (1980) 468-687. 19 S. A. MI~SAK, H. HOEKS~IA, AND L. ht. PSCHIGODA, J. Anribiot., 32 (1979) 771-772. 20 A. K. GANGULY, 0. Z. SARRE, AND H. REIBMNX, J. Am. Chem. Sot., 90 (1968) 7129-7130; A. K. GAXGULY, 0. Z. SARRE, A. T. MCPHZJL, AND K. D. ONAN, Chem. Commw~., (1977) 313-314. 21 H. I. AH&MD, J. S. BRNXOMBE, A. S. MENGECH, AND L. C. N. TUCKER, Carbohydr. Res., 93 (1981) 288-293.