The ddq cleavage of a benzyl ether is a classic transformation, yet it has not always been reliable. Silvericatalyzed deprotection of pmethoxybenzyl ethers. Deprotection akin to protection, the deprotection proceeds through pentacoodinated intermediates. 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.
What are the good and efficient methods for deprotection of 2,4dimethoxybenzylamine dmb and pmb amines. Electrochemical deprotection of paramethoxybenzyl ethers. A facile and efficient protocol for the oxidative deprotection of benzyltype ethers has been developed. In this reaction, the pmb group is removed by oxidation to an aldehyde which, however, may then react with the target product to form an acetal between the positions 2 and 3. 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. 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. 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. A detailed mechanism illustrating benzyl deprotection using hydrogen and palladium on carbon h2, pdc. Facile and selective deprotection of pmb ethers and esters. In the initial screening experiments, the oxidative deprotection of pmb ether of 2octanol 1a was selected as the model reaction. Use pmb to import files to the computer even when you use commercially available software for editing. But avoid asking for help, clarification, or responding to other answers. Thus, we adopted this synthetic strategy and hoped that oxidation cyclization could subsequently happen after the deprotection. Moderna process chem amri chem dev only search this site.
A graphical index of bond types provides links to search for specific transformations of interest and locate examples to use in solving synthetic problems. Benzyl and pmethoxy benzyl protecting groups are ubiquitous in organic synthesis. Sequential removal of the benzyltype protecting groups. The present book, which is a monograph on this operation, is not primarily aimed at specialized researchers interested in the development of new oxidants. Videos and photos saved on the computer cannot be viewed in pmb. A simple method for the selective deprotection of p. Methoxybenzyl mpm protecting group removable by ddq. The protecting groups list contains stability data for the most important groups. 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. Introduction the need for selectivity in retrosynthetic analysis of target molecule chemoselectivity which functional group will react with reagent. A p methoxybenzyl pmb protectiondeprotection approach. Deprotection of benzyl and pmethoxybenzyl ethers by. Deprotection kinetics for fmoc release using 5% piperazine.
This system can be applied for oxidative deprotection of pmb ethers, alcohol oxidation, aromatization and. However, treatment with tfa led to rapid equilibration to afford a 2. What happens to the tbutyl cation in the tfa deprotection. Protecting groups and deprotection oh, cooh, co, nh2 groups. The catalytic oxidation system was established from the aerobic oxidation of nonsterically hindered benzylic alcohols and applied in the oxidative deprotection of pmb ethers.
The use of the internet pages of dlubal software gmbh is possible without any indication of personal data. Dicyanodichloroquinone ddq is the most frequently used and most effective quinone for such applications. Data protection has particularly high importance for the management of dlubal software gmbh. Meoch2ch2och2cl, nah, thf meoch2ch2och2cl, ch2cl2, ipr2etn tl 1976, 809 cleavage lewis acids such as znbr2, ticl4, me2bbr2 c. What are the good and efficient methods for deprotection of 2. Methoxybenzyl mpm protecting groups for hydroxy function were readily and efficiently removed with ddq in ch 2 cl 2h 2 o at room temperature. 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. Consider the reactivity of different hydroxyl groups. Ddq mediated regiospecific protection of primary alcohol and. The results of deprotection of pmb ethers using csinaoh are summarized in table 3.
As shown in scheme, 4methoxybenzyl trichloroacetimidate was successfully applied in the selective preparation of chiral synor antidiamines,5 as well as. Fluoridemediated deprotection of silyl ethers proceeds through a pentavalent silicon pathway. Dimethoxybenzyl dmpm groups were more reactive than mpm with ddq. Protecting groups hydroxyl protecting groups 4 ethers 3. Research scientist lilly cmc manager bms assoc director myokardia scientist sanofi latest internships. This ddq regeneration technique, making use of 3 equiv. Protecting groups 58 methoxyethoxymethyl ethers mem roh roch2och2ch2ome stable to base and mild acid formation. This oxidant is useful for the dehydrogenation of alcohols, phenols, and steroid ketones in organic chemistry. Ddq decomposes in water, but is stable in aqueous mineral acid. Pmb ethers employ stoichiometric excesses of ddq or can scheme 1,6 but various other deprotection methods have been reported. Nah, bnbr, tbai, thfdmf, 94% followed by pmb deprotection ddq, ch 2 cl 2 ph 7 buffer, 95% gave alcohol 10. Rather, it was written with the objective of being a practical guide for any. A very mild and selective method using magnesium bromide alexandros vakalopoulos, and h. An additional softnetcp can be used in unconfigured mode pg mode.
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. There are two dimethoxybenzyl dmb or dmpm groups 2,4dimethoxy and 3,4dimethoxy, both of. 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. Dipyrone approach toward the synthesis of the cytotoxic. The reaction mechanism is unlike the s n 1 path in carbon chemistry as silyl cations are unstable. Protecting groups of hydroxyl groups consider the stability and effect of anomeric group. How can i do the deprotection of pmb on the nitrogen of.
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. Removal of the pmb protecting groups was initially carried out using a standard protocol based on ddq in ch 2 cl 2. Aerobic oxidative deprotection of benzyltype ethers under. 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. Mild, selective deprotection of pmb ethers with triflic acid1,3dimethoxybenzene. 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. Kazunobu toshima of keio university has recently tetrahedron lett. Fecl3 and fecl3sio2 catalysed selective pmethoxybenzylation.
Hoffmann department of organic chemistry, university of hannover, schneiderberg 1 b, d30167 hannover, germany. How can i do the deprotection of pmb on the nitrogen of isatin. Nevertheless, the most widely used method for deprotection involves the oxidative cleavage of the n pmb moiety using ceric ammonium nitrate can. This aerobic catalytic system was established for the selective oxidation of non. 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. 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. 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. 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.
Mild deprotection of pmb ethers using tertbutyl bromide. 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. 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. Under these neutral conditions, other usual protecting and functional groups remained unchanged. Consider the solubility of starting material the choice of solvent.
F pmb can be deprotected either under typical acid or oxidizing conditions. 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. 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. Protecting groups and deprotection oh, cooh, co, nh2. A convenient approach for the deprotection and scavenging of. Chandrasekhar reported the deprotection of pmb 4methoxybenzyl and dmb 3,4dimethoxybenzyl ethers using 10 mol% ddq in combination with 3. D 206b, discovery laboratory, organic chemistry divisioniii, indian institute of chemical technology, hyderabad. Thanks for contributing an answer to chemistry stack exchange. However, the synthesis of 2,4dimethoxybenzyl halides could not be.
Protecting groups and their deprotection linkedin slideshare. Quinonecatalyzed selective oxidation of organic molecules. 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. Dmb ether 34 is deprotected by ddq to give compound 35 without removal of the pmb group. Since ddq is an electron sink, it will then deprotect the carbonoxygen first to provide the chemioselective product. 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. General characteristics 2,2,2trichloroethoxycarbonyl troc group is a commonly used carbamate protecting group for amines. Protecting groups in organic synthesis6 ready pmethoxybenzyl pmb or mpm o o r on. 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.
In summary, a sequential deprotection strategy for sugars has been demonstrated, based upon the pmb, nap and benzyl groups. This allowed selective oxidation of the c1 alcohol with ddq after deprotection to ketone 31. Ceric ammonium nitrate oxidation of npmethoxybenzyl. 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. 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. The driving force of fluoridebased deprotection is the formation of sif bond, which is about 30 kcalmol stronger than sio bond. Configuration limits for products of the simatic net pc software v8. Can nand ddq can be selectively applied for deprotection of pmb. 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. Mild, selective deprotection of pmb ethers with triflic acid. A new catalytic oxidation system using catalytic amounts of 2,3. 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. This allows selective oxidation of the c1 alcohol with ddq after deprotection to ketone 31.
Acidfacilitated debenzylation of nboc, nbenzyl double. Acid cleavagedeprotection in fmoctbiu solidphase peptide. While substrate scope is limited, these catalytic conditions allow for the same selective removal of pmb ether protecting groups as with. Deprotection methods 2,3dichloro5,6dicyano p benzoquinone ddq 16 conditions for deprotection of benzyl group are applicable for cleavage of the pmb protecting group.
Mild, selective deprotection of pmb ethers with triflic. Under the optimal reaction conditions, a variety of pmethoxybenzyl pmb, pphenylbenzyl ppb, and. 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. How can i do the deprotection of pmb on the nitrogen of kainic acid. 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. 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.
Fortunately, ddq involved deprotection and oxidative annulation proceeded well as anticipated, forming the desired product 1,8,9trisbenzyloxy3methoxy6 hbenzofuro3,2cchromen6one 17 in 56% yield. Organic chemistry portal the organic chemistry portal offers an overview of recent topics, interesting reactions, and information on important chemicals for organic chemists. Ddq, can, h2 pdc, lina nh3 nbs pmethoxybenzyl ether pmb. 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. A convenient approach for the deprotection and scavenging of the pmb group using pocl3. This product has been replaced by 270245aldrich 4methoxybenzyl chloride contains potassium carbonate as stabilizer, 98% protecting group reagent for alcohols. Ddq 2,3dichloro5,6dicyanobenzoquinone is a chemical reagent widely used in organic synthesis. 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. 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.