Benzylic functionalization secondary

Some unusual benzylic functional groups can be reduced to hydrocarbons using NaBH4 alone in alcohols (equation 54). Choice of solvent can be used to enhance (or reduce) the reductive power of NaBIL. Thus in DMSO (or sulfolane), NaBH4 effectively reduces primary, secondary and tertiary benzylic halides to alkanes, leaving nitro, ester and carboxylic acids untouched (equation 55). There... 

Selective ortho and benzylic functionalization of secondary and tertiary p-tolylsulfonamides is investigated (eq 47). For both R = H and R = Et, kinetic ortho metalation is achieved using BuLi, while thermodynamic conditions lead to ortho and benzylic deprotonation, respectively. Regioselective metalation of secondary sulfonamides, R = H, is achieved by using BuLi/KOtBu superbase. ... 

Benzylic oxidation of alkoxybenzyl ethers is particularly facile, and since some of the more activated derivatives are cleaved under conditions which leave benzyl, various ester, and formyl groups unaffected, they have found application in the protection of primary and secondary alcohols. Deprotection with DDQ in dichloromethane/water follows the order 3,4-dimethoxy > 4-methoxy > 3,5-dimethoxy > benzyl and secondary > primary, thus allowing the selective removal of one function in the presence of another. 2,6-Dimethoxybenzyl esters are readily cleaved to the corresponding acids on treatment with DDQ in wet dichloromethane at rt, whereas 4-methoxybenzyl esters are stable under these conditions. Oxidative cleavage of N-linked 3,4-dimethoxybenzyl derivatives with DDQ has also been demonstrated. ... 

The combination of a secondary benzyl alcohol with Hf(OTf)4 in nitromethane was a highly effective secondary benzylation system. Secondary benzylation of carbon (aromatic compounds, olefins, an enol acetate), nitrogen (amide derivatives), and oxygen (alcohols) nucleophiles was carried out with a secondary benzyl alcohol and 1 mol % of Hf(OTf)4 in the presence of water. Secondary benzyl alcohols and nucleophiles bearing acid-sensitive functional groups (e.g.,icri-butyldimethylsilyloxy and acetoxy groups and methyl/benzyl esters) could be used for alkylation. Hf(OTf)4 was the most active catalyst for this alkylation, and trifluoromethanesulfonic acid (triflic acid, HOTf) also proved to be a good catalyst. In such cases, the catal)fiic activity of metal triflates and HOTf increased in the order La(OTf)3 [Pg.346]

The construction of the five contiguous stereocenters required for a synthesis of compound 3 is now complete you will note that all of the substituents in compound 5 are positioned correctly with respect to the carbon backbone. From intermediate 5, the completion of the synthesis of the left-wing sector 3 requires only a few functional group manipulations. Selective protection of the primary hydroxyl group in 5 as the corresponding methoxymethyl (MOM) ether, followed by benzylation of the remaining secondary hydroxyl, provides intermediate 30 in 68 % overall yield. It was anticipated all along that the furan nucleus could serve as a stable substi-... 

The completion of the synthesis of key intermediate 2 requires only a straightforward sequence of functional group manipulations. In the presence of acetone, cupric sulfate, and camphorsulfonic acid (CSA), the lactol and secondary hydroxyl groups in 10 are simultaneously protected as an acetonide (see intermediate 9). The overall yield of 9 is 55 % from 13. Cleavage of the benzyl ether in 9 with lithium metal in liquid ammonia furnishes a diol (98% yield) which is subsequently converted to selenide 20 according to Grie-co s procedure22 (see Scheme 6a). Oxidation of the selenium atom... 

With ring G in place, the construction of key intermediate 105 requires only a few functional group manipulations. To this end, benzylation of the free secondary hydroxyl group in 136, followed sequentially by hydroboration/oxidation and benzylation reactions, affords compound 137 in 75% overall yield. Acid-induced solvolysis of the benzylidene acetal in 137 in methanol furnishes a diol (138) the hydroxy groups of which can be easily differentiated. Although the action of 2.5 equivalents of tert-butyldimethylsilyl chloride on compound 138 produces a bis(silyl ether), it was found that the primary TBS ether can be cleaved selectively on treatment with a catalytic amount of CSA in MeOH at 0 °C. Finally, oxidation of the resulting primary alcohol using the Swem procedure furnishes key intermediate 105 (81 % yield from 138). 

Photolabile linkers play an important role in solid-phase organic synthesis (SPOS) due to their stability under both acidic and basic conditions. The ONb photolabile linker was modified to improve cleavage rates and yields Fmoc-Tos-OFI was released in 87% yield after 23 h (Scheme 4) [24]. Specifically, the primary alcohol was changed to a secondary benzylic alcohol and the attachment to the resin was through an alkyl chain as opposed to an amide function. Linker 20 was used for the production of carboxylic acids or carbohydrates. A second example... 

Treatment of the elimination product 107 with triethylamine resulted in smooth isomerization of the olefin, to afford the a,p-unsaturated ketone 108. Ally lie oxidation of 108 then generated the secondary alcohol 109 in 72 % yield. The acetonide and silyl ether functions of 109 were cleaved in one reaction to afford a tetraol intermediate that was regioselectively acylated at the secondary alcohol functions, to provide the triacetate 110 in high yield (89 %). Hydrogenolysis of the benzyl ether... 

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... 

Secondary phosphine oxides are known to be excellent ligands in palladium-catalyzed coupling reactions and platinum-catalyzed nitrile hydrolysis. A series of chiral enantiopure secondary phosphine oxides 49 and 50 has been prepared and studied in the iridium-catalyzed enantioselective hydrogenation of imines [48] and in the rhodium- and iridium-catalyzed hydrogenation functionalized olefins [86]. Especially in benzyl substituted imine-hydrogenation, 49a ranks among the best ligands available in terms of ex. 

Functionalized organozinc halides are best prepared by direct insertion of zinc dust into alkyl iodides. The insertion reaction is usually performed by addition of a concentrated solution (approx. 3 M) of the alkyl iodide in THF to a suspension of zinc dust activated with a few mol% of 1,2-dibromoethane and MeaSiCl [7]. Primary alkyl iodides react at 40 °C under these conditions, whereas secondary alkyl iodides undergo the zinc insertion process even at room temperature, while allylic bromides and benzylic bromides react under still milder conditions (0 °C to 10 °C). The amount of Wurtz homocoupling products is usually limited, but increases with increased electron density in benzylic or allylic moieties [45]. A range of poly-functional organozinc compounds, such as 69-72, can be prepared under these conditions (Scheme 2.23) [41]. 

The benzyne route to dibenzopyrrocoline alkaloids with the 1-benzyltetrahy-droisoquinolines (40) listed in Table II was investigated by Kametani et al. (28), Kessar et al. (29), and Gibson and Ahmed (31). Secondary amines protected as 7-0-benzyl ethers, affording unstable tetrahydro intermediates with benzyl ether functions difficult to deprotect, were less favored than the corresponding N-methyl-substituted analogs, affording the desired quartemary alkaloids directly. 

Stoicheiometric RuOyCCl was also used to oxidise several furanoses, partially acylated glycosides and l,4 3,6-dianhydrohexitols [317] pyranosides to pyrano-siduloses [313] methyl 2,3,6-tri-O-benzoyl-a-D-glucopyranoside and its C-4 epimer to the a-D-xy/o-hexapyranosid-4-ulose (Table 2.3) [317], and methyl 2,3,6-trideoxy-a-D-e 7f/tro-hexapyranoside to the -a-D-,g/yceri9-hexa-pyranosid-4-ulose, an intermediate in the synthesis of forosamine [318], It was also used to oxidise benzyl 6-deoxy-2,3-0-isopropylidene-a-L-mannopyranoside to the a-L-/yxo-hexapyranosid-4-ulose [319] and for oxidation of isolated secondary alcohol functions, e.g. in the conversion of l,6-anhydro-2,3-0-isopropylidene-P-D-man-nopyranose to the-P-D-/yxo-hexa-pyranos-4-ulose mannopyranose (Fig. 2.16, Table 2.3 [20, 320, 324]). 

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