Interestingly, can is found to be superior to ddq for the selective removal of the pmb versus nap group, whereas ddq is more efficient for the deprotection of nap in the presence of a benzyl group. But avoid asking for help, clarification, or responding to other answers. A convenient approach for the deprotection and scavenging of. Ddq 2,3dichloro5,6dicyanobenzoquinone is a chemical reagent widely used in organic synthesis. Protecting groups in organic synthesis6 ready pmethoxybenzyl pmb or mpm o o r on. Deprotection of benzyl and pmethoxybenzyl ethers by. This ddq regeneration technique, making use of 3 equiv. Research scientist lilly cmc manager bms assoc director myokardia scientist sanofi latest internships. Use pmb to import files to the computer even when you use commercially available software for editing. How can i do the deprotection of pmb on the nitrogen of. Under the optimal reaction conditions, a variety of pmethoxybenzyl pmb, pphenylbenzyl ppb, and.
Ddq decomposes in water, but is stable in aqueous mineral acid. Rather, it was written with the objective of being a practical guide for any. The most common use of ddq in synthetic chemistry is the oxidative removal of pmethoxy benzyl groups, which allows the use of pmb as a protecting group orthogonal to almost all others. Hoffmann department of organic chemistry, university of hannover, schneiderberg 1 b, d30167 hannover, germany. Furthermore, swift deprotection of 2, 7dimethylpixyl dmpx is accomplished with ddq. The pmb group was easily and selectively removed in 6898% yield using tfa in dcm. Consider the solubility of starting material the choice of solvent. Anhydrous fecl3 and fecl3sio2 serve as lewis acids for direct conversion of alcohols into pmethoxybezyl ethers using pmb oh in good yields, the latter reagent was found to be effective in not only converting primary, allylic and propargylic alcohols selectively but also the preexisting acid sensitive groups remained unscathed. Protecting groups and deprotection oh, cooh, co, nh2. Methoxybenzyl mpm protecting group removable by ddq. Acid cleavagedeprotection in fmoctbiu solidphase peptide. General characteristics 2,2,2trichloroethoxycarbonyl troc group is a commonly used carbamate protecting group for amines. The pmethoxybenzyl pmb ethers and their somewhat less acid sensitive congeners, the 2naphthylmethyl nap ethers, are staple protecting groups in organic synthesis in general, and especially in oligosaccharide synthesis, owing to their facile oxidative cleavage with either dichlorodicyanoquinone ddq or ceric ammonium nitrate can.
Pmb ethers employ stoichiometric excesses of ddq or can scheme 1,6 but various other deprotection methods have been reported. Jun 28, 2017 a simple and efficient protocol is described for regiosepecific protection of primary hydroxyl group both in nucleosides and other molecules with pmethoxybenzyl 2,7dimethyl pixylether mbdpe in presence of 2,3dichloro5,6dicyano1,4benzoquinone ddq. Oxidation to the methyl ketone8 dessmartin periodinane, py, ch 2 cl 2, 93%, and hydrazone formation tmscl, ch 2 cl 2 me 2 nnh 2, 100% completed the synthesis of hydrazone 11. The pmethoxybenzyl group pmb is one of the widely used hydroxyl protecting groups which shows orthogonality against a variety of protecting groups, including benzyl ethers, depending upon the deprotection method employed. F pmb can be deprotected either under typical acid or oxidizing conditions. What are the good and efficient methods for deprotection of 2.
Ddq mediated regiospecific protection of primary alcohol and. The driving force of fluoridebased deprotection is the formation of sif bond, which is about 30 kcalmol stronger than sio bond. Videos and photos saved on the computer cannot be viewed in pmb. This allows selective oxidation of the c1 alcohol with ddq after deprotection to ketone 31. Feb 04, 2012 ddq oxidation can be a much cleaner reaction, as it was reported that the 2,4dimethoxybenzyl protecting group of bocprotected amines can be easily deprotected by ddq. Consider the reactivity of different hydroxyl groups. The cleavage of the pmb instead of the tbdps deprotection group will occur because, under oxidative conditions, the ddq s electrons will be more attracted towards the co bond. Can nand ddq can be selectively applied for deprotection of pmb. A convenient approach for the deprotection and scavenging of the pmb group using pocl3. However, employment of these protecting groups commonly requires use of acidic or basic reaction media and or otherwise nonmild reaction conditions, which sometimes are not compatible with other functional groups in the molecule. The major functions of ddq include the deprotection of thioacetals,acetals and ketals and conversion to aldehydes and ketones,1 and the deprotection of benzyl, mpm 4.
However, treatment with tfa led to rapid equilibration to afford a 2. Data protection has particularly high importance for the management of dlubal software gmbh. This compound is alkylated to 32 at the c1 ketone group with the grignard homoallyl magnesium bromide c4 fragment completing the carbon framework and deprotected at c11 tbaf to diol 33. While substrate scope is limited, these catalytic conditions allow for the same selective removal of pmb ether protecting groups as with.
Benzyl and pmethoxy benzyl protecting groups are ubiquitous in organic synthesis. An additional softnetcp can be used in unconfigured mode pg mode. After 30 min, the reaction mixture was warmed to room temperature and further stirred for the specified time table 2 before it was diluted with ch 2 cl 2 and quenched with sat. In summary, a sequential deprotection strategy for sugars has been demonstrated, based upon the pmb, nap and benzyl groups. Deprotection of pmethoxybenzyl and 3,4 dimethoxybenzyl protecting groups pmethoxybenzyl pmb and 3,4dimethoxybenzyl dmbgroups are removed by the treatment with ddq in ch2cl2h20 under neutral conditions scheme 5. The reaction mechanism is unlike the s n 1 path in carbon chemistry as silyl cations are unstable. A p methoxybenzyl pmb protectiondeprotection approach. A new catalytic oxidation system using catalytic amounts of 2,3. Nov 21, 2009 reaction times of 36 h and overall yields of 7898% were achieved with the pmb group in place compared to no reaction without this protecting group. A new biomimetic catalytic oxidation system which employs 2,3dichloro5,6dicyano1,4benzoquinone ddq as the catalyst, molecular oxygen as the terminal oxidant and ironii phthalocyanine fe ii pc as the electrontransfer mediator has been developed.
Under the optimal reaction conditions, a variety of pmb ethers can be deprotected in high conversions to their corresponding alcohols with high selectivities. Protecting groups hydroxyl protecting groups 4 ethers 3. Under these neutral conditions, other usual protecting and functional groups remained unchanged. If you want to use pmb to view videos and photos saved without using pmb, you must use pmb to specify the folder where the videos and photos are. Mild, selective deprotection of pmb ethers with triflic acid1,3dimethoxybenzene.
Electrochemical deprotection of paramethoxybenzyl ethers. Sequential removal of the benzyltype protecting groups. Thanks for contributing an answer to chemistry stack exchange. Nevertheless, the most widely used method for deprotection involves the oxidative cleavage of the n pmb moiety using ceric ammonium nitrate can. A detailed mechanism illustrating benzyl deprotection using hydrogen and palladium on carbon h2, pdc. D 206b, discovery laboratory, organic chemistry divisioniii, indian institute of chemical technology, hyderabad. The deprotection of benzyl ethers was effectively realized in the presence of 2,3dichloro5,6dicyanopbenzoquinone ddq in mecn under photoirradiation using a long wavelength uv light. The reaction was performed with catalytic amounts of 2,3dichloro5,6dicyano1,4benzoquinone ddq and tertbutyl nitrite tbn under atmospheric pressure of o 2. The results of deprotection of pmb ethers using csinaoh are summarized in table 3. Lewis acids such as znbr 2, ticl 4, me 2bbr 2 meoch 2ch 2och 2cl, ch 2cl 2, ipr 2etn stable to base and mild acid roh roch2och2ch2ome. This oxidant is useful for the dehydrogenation of alcohols, phenols, and steroid ketones in organic chemistry. How can i do the deprotection of pmb on the nitrogen of kainic acid.
A very mild and selective method using magnesium bromide alexandros vakalopoulos, and h. Protecting groups and deprotection oh, cooh, co, nh2 groups. Nah, bnbr, tbai, thfdmf, 94% followed by pmb deprotection ddq, ch 2 cl 2 ph 7 buffer, 95% gave alcohol 10. A convenient and high yielding approach for the deprotection and scavenging of the pmethoxybenzyl pmb group in pmb ethers and pmb esters was developed using pocl 3 as the reagent. The protecting groups list contains stability data for the most important groups. Mild, selective deprotection of pmb ethers with triflic acid. Since ddq is an electron sink, it will then deprotect the carbonoxygen first to provide the chemioselective product. Protecting groups and their deprotection linkedin slideshare. Protecting groups of hydroxyl groups consider the stability and effect of anomeric group. The resulting mixture was stirred under and atmosphere of h2 for 72 h, after which time it was filtered through a pad of celite eluting with etoac. Dmb ether 34 is deprotected by ddq to give compound 35 without removal of the pmb group.
Deprotection kinetics for fmoc release using 5% piperazine. The present book, which is a monograph on this operation, is not primarily aimed at specialized researchers interested in the development of new oxidants. Quinonecatalyzed selective oxidation of organic molecules. What happens to the tbutyl cation in the tfa deprotection. Fecl3 and fecl3sio2 catalysed selective pmethoxybenzylation. I do not have experience with isatin and i do not know how the co will survive, but benzyl and pnb we were very successfully removing them from tetrazole see. This allowed selective oxidation of the c1 alcohol with ddq after deprotection to ketone 31.
Thus, we adopted this synthetic strategy and hoped that oxidation cyclization could subsequently happen after the deprotection. Fortunately, ddq involved deprotection and oxidative annulation proceeded well as anticipated, forming the desired product 1,8,9trisbenzyloxy3methoxy6 hbenzofuro3,2cchromen6one 17 in 56% yield. Facile and selective deprotection of pmb ethers and esters. Meoch2ch2och2cl, nah, thf meoch2ch2och2cl, ch2cl2, ipr2etn tl 1976, 809 cleavage lewis acids such as znbr2, ticl4, me2bbr2 c. However, the synthesis of 2,4dimethoxybenzyl halides could not be. Ceric ammonium nitrate oxidation of npmethoxybenzyl. Organic chemistry portal the organic chemistry portal offers an overview of recent topics, interesting reactions, and information on important chemicals for organic chemists. Dmap attacks a carbonyl site on ditertbutyl dicarbonate resulting in tertbutyl carbonate leaving as a leaving group the amine attacks the carbonyl site on the bocpyridinium species resulting in the release of dmap catalytic. Methoxybenzyl mpm protecting groups for hydroxy function were readily and efficiently removed with ddq in ch 2 cl 2h 2 o at room temperature.
The pmethoxybenzyl protecting group pmb on various alcohols and an acid was efficiently and selectively cleaved by the action of a catalytic amount of silveri hexafluoroantimonate combined with 0. Deprotection of the pmb ether of the dipyrone 7 with ddq provided the alcohol 3 in 78% yield, which was subjected to crimmins conditions6 for spiroketalization. Introduction the need for selectivity in retrosynthetic analysis of target molecule chemoselectivity which functional group will react with reagent. A facile and efficient protocol for the oxidative deprotection of benzyltype ethers has been developed.
The use of the internet pages of dlubal software gmbh is possible without any indication of personal data. It can also be deprotected under mildly oxidizing conditions using ddq dichlorodicyanobenzoquinone or strongly acidic conditions. Kazunobu toshima of keio university has recently tetrahedron lett. Ddq, can, h2 pdc, lina nh3 nbs pmethoxybenzyl ether pmb. This product has been replaced by 270245aldrich 4methoxybenzyl chloride contains potassium carbonate as stabilizer, 98% protecting group reagent for alcohols. Acidfacilitated debenzylation of nboc, nbenzyl double. In the initial screening experiments, the oxidative deprotection of pmb ether of 2octanol 1a was selected as the model reaction. Mild, selective deprotection of pmb ethers with triflic. Deprotection methods 2,3dichloro5,6dicyano p benzoquinone ddq 16 conditions for deprotection of benzyl group are applicable for cleavage of the pmb protecting group. A simple method for the selective deprotection of p. The reactivity of f pmb and conventional pmb are so similar that a 3,4 dimethoxybenzyl dmb protecting group has been selectively cleaved in the presence of both f pmb and pmb scheme 2.
A graphical index of bond types provides links to search for specific transformations of interest and locate examples to use in solving synthetic problems. Removal of the pmb protecting groups was initially carried out using a standard protocol based on ddq in ch 2 cl 2. Results and discussion by applying it to the oxidative deprotection of pmb ethers, we study the feasibility of the ddq fe ii pco 2 system. Protectiondeprotection of cyclic carbamate on phenyl ring 1a,b via different methods the compounds 2a,b10a,b,inscheme 1, were synthetized by methods a or b, according the reagent desired, with 23hbenzoxazolone 1aor23hbenzothiazolinone 1b. Aerobic oxidative deprotection of benzyltype ethers under. Dimethoxybenzyl dmpm groups were more reactive than mpm with ddq. Protecting groups 58 methoxyethoxymethyl ethers mem roh roch2och2ch2ome stable to base and mild acid formation. Deprotection akin to protection, the deprotection proceeds through pentacoodinated intermediates. This compound was alkylated to 32 at the c1 ketone group with the grignard homoallyl magnesium bromide c4 fragment completing the carbon framework and deprotected at c11 tbaf to diol 33.
What are the good and efficient methods for deprotection of 2,4dimethoxybenzylamine dmb and pmb amines. There are two dimethoxybenzyl dmb or dmpm groups 2,4dimethoxy and 3,4dimethoxy, both of. In general, a solidphase peptide synthesis spps consists of the assembly of a protected peptide chain on a polymeric support synthetic step and the subsequent cleavage deprotection to release the crude, deprotected peptide from the solid support cleavage step. How can i do the deprotection of pmb on the nitrogen of isatin. This aerobic catalytic system was established for the selective oxidation of non. Moderna process chem amri chem dev only search this site. The catalytic oxidation system was established from the aerobic oxidation of nonsterically hindered benzylic alcohols and applied in the oxidative deprotection of pmb ethers. We examined the cleavage of pmethoxybenzyl protected alcohols and phenols in the presence of a double bond under the csinaoh reaction conditions used in the deprotection of benzyl ethers. Mild deprotection of pmb ethers using tertbutyl bromide. The cleavage of the pmb instead of the tbdps deprotection group will occur because, under oxidative conditions, the ddq s electrons will be more attracted towards the c. Chandrasekhar reported the deprotection of pmb 4methoxybenzyl and dmb 3,4dimethoxybenzyl ethers using 10 mol% ddq in combination with 3.