Protective groups methoxymethyl

PROBLEM 16.65 This problem introduces another alcohol protecting group, methoxymethyl (MOM), particularly popular in the month of May. The MOM protecting group is stable to... 

The cleavage proceeds by initial reduction of the nitro groups followed by acid-catalyzed cleavage. The DNB group can be cleaved in the presence of allyl, benzyl, tetrahydropyranyl, methoxy ethoxy methyl, methoxymethyl, silyl, trityl, and ketal protective groups. 

Treatment of 8-azidomethylperhydropyrido[l,2-c]pyrimidin-l-one 157 with methyl triflate and catalytic hydrogenation of the azide group led to the formation of tricyclic guanidine derivative 158 (01JA8851). Hydroxy group of 149 was protected with methoxymethyl chloride, and the p-methoxybenzyl protecting group (PMB) was eliminated by treatment with DDQ. 

The methoxymethyl ether protecting groups of 33 were then cleaved using triphenylphosphine and carbon tetrabromide. The resulting hydroquinone function was oxidized by palladium on carbon under an atmosphere of air to afford the quinone 52 (70 %). A two-step procedure was implemented to install the diazo function. First, the ketone function of 52 was condensed with N,N -bis( tert-butyldimethylsilyl)hydrazine in the presence of scandium triflate, which formed the Af-tert-butyldimethylsilyl hydrazone 53. The hydrazone (53) was then oxidized using difluoroiodobenzene to afford kinamycin C (3) in 35 % yield. 

Our retrosynthesis of (—)-kinamycin F (6) is shown in Scheme 3.20 [45]. It was envisioned that (—)-kinamycin F (6) could be prepared from the protected diazofluorene 114 by conversion of the ketone function of 114 to a trans-], 2-diol, followed by deprotection of the acetonide and methoxymethyl ether protecting groups. The diazofluorene 114 was envisioned to arise from diazo transfer to the hydroxyfulvene 115. The cyclopentadiene substructure of 115 was deconstructed by a two-step annulation sequence, to provide the bromoquinone 116 and the p-trimethylsilylmethyl unsaturated ketone 117. The latter two intermediates were prepared from juglone (118) and the silyl ether 119, respectively. 

In some instances, treatment of polyfunctional benzylic alcohols with acid in the presence of organosilicon hydrides causes multiple functional group transformations to occur simultaneously. This phenomenon is illustrated by the reduction of the secondary benzylic alcohol function and concomitant loss of the methoxymethyl protecting group of 2-(l-hydroxydecyl)-5-methoxy-l-(methoxy-methyleneoxy)naphthalene upon treatment with Et3SiH/TFA in dichloromethane (Eq. 26).167... 

Other acetal-type protecting groups (tetrahydrofurfuryl ethers, methoxymethyl ethers, 1,3-dioxolanes) are also considered to be incompatible with oxidising agents. 

Comins and Killpack have also investigated the lithiation of a small number of N-protected indole-3-carboxaldehydes, using lithium N-methyl-piperazide to form the a-amino alkoxide, and found that decomposition occurred with the A -benzenesulfonyl, N-ter/-butoxycarbonyl, and A -di-methylcarbamyl derivatives (87JOC104). Success was achieved with the N-methoxymethyl derivative 19, although no attempt was made to subsequently remove the normally difficult to hydrolyze methoxymethyl protecting group. Therefore the real viability of this method as a route to... 

A straightforward synthesis (Scheme 3) of a furocoumarin-thymidine furan-side adduct was developed <1997JOC2630>. The methoxymethyl (MOM)-protecting group in 33 was removed in 91% yield with ethanolic HCl, and the resulting phenol 34 was condensed with dimethylacetamide dimethyl acetal in the presence of 4 A... 

N-alkylation and N-acylation of piperazine-2,5-diones are quite common and have been routinely employed in several synthetic sequences (see Section IV,C). Such operations have also been performed as measures for the temporary protection of the nitrogen during further synthetic maneuvers in other parts of the molecule. Three different alkyl groups have been employed as such protecting groups. Kishi has used the methoxymethyl group for N-protection (potassium r-butoxide, chloro-methyl methyl ether 0°C, 75% yield). Deprotection was achieved by cone. HCl-ethanol at reflux temperature (81T2045). 

A methoxymethyl [MOM] protecting group at C-2 could not be removed following esterification ... 

A methoxymethyl (MOM) protecting group at N-3 was chosen based on its successful use in the total synthesis of nucleoside Q.31 Our previous experience with the total synthesis of rigidin vide supra) suggested BOM protection for the N-1 position and a 2,4-dimethoxybenzyl (DMB)... 

---