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New synthetic ‘tricks’. Trimethylsilyl triflate mediated cleavage of hindered silyl ethers
Tetmhdm Lettax, Vo1.31, No.4, pp 567-W. PlilltCdinorutBrit.¶h
oo404039190
1990
Perg-
New Synthetic ‘Tricks’. Trimethylsilyl
$3.00 + .oa
PreEsplc
Triflate Mediated Cleavage of Hindered Silyl Ethers
Valentf Bou and Jaume Vilarmsa Departament de Qufmica Or&&a, Facultat de Qufmica, Universitat de Barcelona(III), 08028 Barcelona, Catalonia, Spain
Summary.- An alternative, mild procedure for the cleavage of t-butyldimethylsilyl and triphenylsilyl ethers to alcohols is shown, which is based on an exchange reaction w&h trimethylsilyl@late below 0 C t-Butyldiphenylsilylgroups are not removed under these con&ions. The tert-butyklimethylsilyl group (Bu%ie#i, TBDMS) has become the most outstanding member of a very useful set of silicon-based protective groups for alcohols.1 The corresponding silyl ethers may be cleaved by several reagents among which ButN+F-nH20 (in THF at r.t.) is frequently used. However, even this almost perfect deprotection method has some limitations, due to the basicity of the ‘naked’ fluoride ion, which may promote transacylations in 0-acyl-protected sugars and polyols2 and other undesired reactions.1
In connection with a work aimed at synthesizing novel nucleosides3 we required alternative procedures to deprotect Bu’MezSi ethers. On the basis of the known fact that Me3SiI cleaves dialkyl ethers to afford alkyl iodide(s),4 we envisaged the possibility of exchange reactions between silyl ethers and trimethylsilyl trillate (MesSiOTf, TMSOTf) such as the following example, in which the poor nucleophilicity of iriflate anion would preclude the formation of alkyl triflate from the intermediate oxonium ion: ButMe$i-O-R
+ Me3SiOTf =
[ ButMe#i-9+-R ] ti MgSi TfO-
MesSi-O-R
+ BuMe2SiOTf
If by steric and/or electronic reasons these equilibria were shifted to the right, addition of either water or methanol would readily cleave the much more prone-tohydrolysis trirnethylsilyl ethers (MegSi-O-R). We wish to report here our results regarding this point. Treatment of 0.5 mmol of compounds la5a with Me$iOTf (1.0-2.5 mmol depending on the case; see the Table in the next page), in 3-5 ml of cold anh. CH2C12 under argon,for afar minutes, followed by addition of neutral alumina (grade I) to the reaction flask and filtmtion of the mixture through a small pad of alumina with CH$Z12/MeOH 98:2 or 9O:lO as eluents, afforded deprotected nucleosides 1-3, glucose derivative 4, and cholesterol (S), respectively, in almost quantitative yields.5 0
0
RO
1, R=H la, R = Bu’Me$li
2a, R= Bu’Me2Si
Analogously, but below 0 “C to avoid byproducts, the triphenylsilyl groups (PhgSi, TPS) of 4b and 5b can be readily removed, as shown in the Table.5 No transacylation is observed in the 4a and 4b cases.
567
568
0 H*N
A R'O
J)I
N
Y RO
3, 3a,
R=R’=H
R=R’=Bu’Me$ji
OM8 4, R=H 4a, R = BufMczSi 4b,R=PhsSi
5, R=H Sa, R = Bu’Me#i 5b, R=PhsSi
3b, R=Bu%iezSi, R’=BuTh#i 3c,
R=H, R’=BuTh#i
The simplicity of the procedure is worth noting; moreover, it takes less than 1 h, including the workup, and the reaction is fast even at -78 “C. We think that other moderately hindered R3Si protective groups may also be amenable to this cleavage method. On the other hand, the corresponding ButPh2S i (TBDPS) ethers are much less reactive since under our conditions even secondary ButMepSiOR may be cleaved without touching primary ButPh2SiOR (see 3b3c).e Attempts to remove Bu’PhzSi, warming up to r.t., caused partial decomposition of the samples.7
Table. Cleavage of Silyl Ethers to Alcohols substrate
MqSiOTf (no.equiv) 3 3 5 5 3 2 3 3 3
time @ia) 5 5 5 30 5 10 30 30 15
temp. 0 0 0 0 -78 0 0 -10 -20 -20
product
yielda (%) 98 86-92 95 90-95 97 95 90 96 86
1 la 2 2a 3 3a 3 3a 4 4a 5 5a 4 4b 5 5b 3c 3b =Yieldof isolated product; 97-1009b crude yiekls (1H NMR) in all cases.
Acknowledgments. We thank the CIRIT (Generalitat de Catalunya, Barcelona) and CICYT (Ministerio de Educaci6n y Ciencra, Madrid) for financial support during 1986-87 and for 198890 (Grant PB860137), respectively. A fellowship to V. B. (1988-91) from the Ministerio de Educacidn y Ciencia is also deeply acknowledged. References and footnotes 1. For recent reviews, see: ‘Silylating Agents’; Fluka Chemie; Buchs. 1988. Lalonde, M.; Chan, T. H. Synthesis 1985.817. 2. 3. 4. 5. 6.
7.
Also see: Pmkash, C.; Saleh. S.; Blair, I. A. Tetrahedron Len. 1989.30,19, and references therein. Franke, F.: Guthrie. R. D. Ausr. J. Chem. 1978.31. 1285. Dodd, G. H.; Golding, B. T.; Ioannou, P. V. 1. C/rem. Sot.. Chcm. Commun. 1975, 249. Bou, V.; Garc& J.; Vilanasa, J. Work in progress (Grant PB86-0137). Jung, M. E.; Lyster, M. A. J. Org. Chum. 1977.42.3761.
Review: Bhatt, M. V.; Kulkami. S. U. Synthesis 1983.249.
The substrates studied here are not signiilcantiy depmtected by column chromatography (alumina, CH2Cl2hfeOH). i.e. without previous addition of TMSOTf. By identical treatment of la with3 equiv. of TfGH. it is only observed a partial depmtection. Prakash et al. (ref. 1) have just mported that pyridinium p-toluenesulphonate in EtOH at r.t. also removes selectively TBDMS groups in the presence of TBDPS ones Looking for similar facts in me literatme, in a paper on the cleavage of MOM ethers by uimethylsilyl bromide (Hanessian. S.; Delorme, D.; Dufresne, Y. Terrahedron Len. 1984.25, 2515) it is incidentally mentioned that me TBDPS ethers were stable whereas die TBDMS ones were partiaBy stable. Si-C cleavages seem to take place. Exchange experiments between TMSOTf and PhCH2CH20SiRg (where SiR3 = TMS, TBDMS, TPS, OTTBDPS) have been monitored by XXl-MHz 1H NMR and will be mported elsewhere.
(Received in UK 13 November 1989)
oo404039190
1990
Perg-
New Synthetic ‘Tricks’. Trimethylsilyl
$3.00 + .oa
PreEsplc
Triflate Mediated Cleavage of Hindered Silyl Ethers
Valentf Bou and Jaume Vilarmsa Departament de Qufmica Or&&a, Facultat de Qufmica, Universitat de Barcelona(III), 08028 Barcelona, Catalonia, Spain
Summary.- An alternative, mild procedure for the cleavage of t-butyldimethylsilyl and triphenylsilyl ethers to alcohols is shown, which is based on an exchange reaction w&h trimethylsilyl@late below 0 C t-Butyldiphenylsilylgroups are not removed under these con&ions. The tert-butyklimethylsilyl group (Bu%ie#i, TBDMS) has become the most outstanding member of a very useful set of silicon-based protective groups for alcohols.1 The corresponding silyl ethers may be cleaved by several reagents among which ButN+F-nH20 (in THF at r.t.) is frequently used. However, even this almost perfect deprotection method has some limitations, due to the basicity of the ‘naked’ fluoride ion, which may promote transacylations in 0-acyl-protected sugars and polyols2 and other undesired reactions.1
In connection with a work aimed at synthesizing novel nucleosides3 we required alternative procedures to deprotect Bu’MezSi ethers. On the basis of the known fact that Me3SiI cleaves dialkyl ethers to afford alkyl iodide(s),4 we envisaged the possibility of exchange reactions between silyl ethers and trimethylsilyl trillate (MesSiOTf, TMSOTf) such as the following example, in which the poor nucleophilicity of iriflate anion would preclude the formation of alkyl triflate from the intermediate oxonium ion: ButMe$i-O-R
+ Me3SiOTf =
[ ButMe#i-9+-R ] ti MgSi TfO-
MesSi-O-R
+ BuMe2SiOTf
If by steric and/or electronic reasons these equilibria were shifted to the right, addition of either water or methanol would readily cleave the much more prone-tohydrolysis trirnethylsilyl ethers (MegSi-O-R). We wish to report here our results regarding this point. Treatment of 0.5 mmol of compounds la5a with Me$iOTf (1.0-2.5 mmol depending on the case; see the Table in the next page), in 3-5 ml of cold anh. CH2C12 under argon,for afar minutes, followed by addition of neutral alumina (grade I) to the reaction flask and filtmtion of the mixture through a small pad of alumina with CH$Z12/MeOH 98:2 or 9O:lO as eluents, afforded deprotected nucleosides 1-3, glucose derivative 4, and cholesterol (S), respectively, in almost quantitative yields.5 0
0
RO
1, R=H la, R = Bu’Me$li
2a, R= Bu’Me2Si
Analogously, but below 0 “C to avoid byproducts, the triphenylsilyl groups (PhgSi, TPS) of 4b and 5b can be readily removed, as shown in the Table.5 No transacylation is observed in the 4a and 4b cases.
567
568
0 H*N
A R'O
J)I
N
Y RO
3, 3a,
R=R’=H
R=R’=Bu’Me$ji
OM8 4, R=H 4a, R = BufMczSi 4b,R=PhsSi
5, R=H Sa, R = Bu’Me#i 5b, R=PhsSi
3b, R=Bu%iezSi, R’=BuTh#i 3c,
R=H, R’=BuTh#i
The simplicity of the procedure is worth noting; moreover, it takes less than 1 h, including the workup, and the reaction is fast even at -78 “C. We think that other moderately hindered R3Si protective groups may also be amenable to this cleavage method. On the other hand, the corresponding ButPh2S i (TBDPS) ethers are much less reactive since under our conditions even secondary ButMepSiOR may be cleaved without touching primary ButPh2SiOR (see 3b3c).e Attempts to remove Bu’PhzSi, warming up to r.t., caused partial decomposition of the samples.7
Table. Cleavage of Silyl Ethers to Alcohols substrate
MqSiOTf (no.equiv) 3 3 5 5 3 2 3 3 3
time @ia) 5 5 5 30 5 10 30 30 15
temp. 0 0 0 0 -78 0 0 -10 -20 -20
product
yielda (%) 98 86-92 95 90-95 97 95 90 96 86
1 la 2 2a 3 3a 3 3a 4 4a 5 5a 4 4b 5 5b 3c 3b =Yieldof isolated product; 97-1009b crude yiekls (1H NMR) in all cases.
Acknowledgments. We thank the CIRIT (Generalitat de Catalunya, Barcelona) and CICYT (Ministerio de Educaci6n y Ciencra, Madrid) for financial support during 1986-87 and for 198890 (Grant PB860137), respectively. A fellowship to V. B. (1988-91) from the Ministerio de Educacidn y Ciencia is also deeply acknowledged. References and footnotes 1. For recent reviews, see: ‘Silylating Agents’; Fluka Chemie; Buchs. 1988. Lalonde, M.; Chan, T. H. Synthesis 1985.817. 2. 3. 4. 5. 6.
7.
Also see: Pmkash, C.; Saleh. S.; Blair, I. A. Tetrahedron Len. 1989.30,19, and references therein. Franke, F.: Guthrie. R. D. Ausr. J. Chem. 1978.31. 1285. Dodd, G. H.; Golding, B. T.; Ioannou, P. V. 1. C/rem. Sot.. Chcm. Commun. 1975, 249. Bou, V.; Garc& J.; Vilanasa, J. Work in progress (Grant PB86-0137). Jung, M. E.; Lyster, M. A. J. Org. Chum. 1977.42.3761.
Review: Bhatt, M. V.; Kulkami. S. U. Synthesis 1983.249.
The substrates studied here are not signiilcantiy depmtected by column chromatography (alumina, CH2Cl2hfeOH). i.e. without previous addition of TMSOTf. By identical treatment of la with3 equiv. of TfGH. it is only observed a partial depmtection. Prakash et al. (ref. 1) have just mported that pyridinium p-toluenesulphonate in EtOH at r.t. also removes selectively TBDMS groups in the presence of TBDPS ones Looking for similar facts in me literatme, in a paper on the cleavage of MOM ethers by uimethylsilyl bromide (Hanessian. S.; Delorme, D.; Dufresne, Y. Terrahedron Len. 1984.25, 2515) it is incidentally mentioned that me TBDPS ethers were stable whereas die TBDMS ones were partiaBy stable. Si-C cleavages seem to take place. Exchange experiments between TMSOTf and PhCH2CH20SiRg (where SiR3 = TMS, TBDMS, TPS, OTTBDPS) have been monitored by XXl-MHz 1H NMR and will be mported elsewhere.
(Received in UK 13 November 1989)