Tertiary benzylic derivatives

MeOH, reagent prepared by heating Bu2SnO and Bu3SnP04, heat 2 h, 90% yield." This method is effective for primary, secondary, tertiary, benzylic, and allylic THP derivatives. The MEM group and ketals are inert to this reagent, but TMS and TBDMS ethers are cleaved. 

Cl3SiH, Et3N, CH2CI2,4-48 h, 25-80°, 80-95% yield. Primary, secondary, tertiary, allylic, propargylic, or benzylic derivatives are cleaved by this method. 

Tertiary amides derived from pyrrole, indole and carbazole were hydro-genolyzed to alcohols and amines by refluxing in ether with a 75% excess (0.88 mol) of lithiwn aluminum hydride. Benzoyl derivatives of the above heterocycles afforded 80-92.5% yields of benzyl alcohol and 86-90% yields of the amines [7704]. 

The aromatic substituent effect on the stereoselectivity has been studied for the condensed-phase and gas-phase acid-induced methanolysis of 2-aryloxiranes derived from 3,4-dihydronaphthalene and turns-1,2.3.4.4a. 1 Oa-hcxahydrophcnanthrcnc bearing a tertiary benzylic oxirane centre.31 Linear free energy relationships were applied successfully. 

The ozone-mediated reaction of bicumene and some derivatives (11) with nitrogen dioxide in dichloromethane (kyodai nitration) at low temperatures results in the cleavage of the central C—C bond to yield the benzyl nitrate and products therefrom, in contrast to the behaviour of bibenzyl.36 This result is interpreted in terms of electron transfer from the substrate to NO3- to give a radical cation species which fragments to form tertiary benzylic species in the former cases. 

Stratmann, O. Kaiser, B. Frohlich, R. Meyer, O. Hoppe, D. The configurational stability of an enantioenriched a-thiobenzyllithium derivative and the stereochemical course of its electrophilic substitution reactions synthesis of enantiomerically pure, tertiary benzylic thiols. Chem. Eur. J. 2001, 7, 423 35. 

The simplest example of this type of system is the benzyl derivative, C6H5CH2LiB2, where B is a coordinated tertiary amine. Two structural... 

Baneijee et al.66 have developed an alternative synthesis of the compound (129) whose utility in synthesis of Mansonone F (120) has been reported by Suh and collaborators.65 This is described in Scheme 13. Tetralone (127) was reduced with sodium borohydride to alcohol which on alkylation with benzyl chloride produced benzyl derivative (132). Its conversion to (133) was attempted by treatment with boron tribromide in dichloromethane. C ompound (133) (characterized b y m ass s pectroscopy) was obtained in poor yield. The major product was the diol (134), whose structure was confirmed by spectral data. It indicates that the demethylation was accompanied by debenzylation. Treatment of diol (134) with triethyl orthoformate and aluminium chloride afforded aldehyde (135) which was subjected to catalytic hydrogenation to produce compound (136). It was transformed to ketone (137) by oxidation and then made to react with methylmagnesium bromide in ether. The resulting tertiary alcohol on heating with p-toluenesulfonic acid in toluene for 24 hr produced the naphthalene (129) in 78% yield. 

Secondary and tertiary alcohols derived from benzyl alcohol, and also tertiary aliphatic alcohols, afford olefins when heated for 9-10 hours in dimethyl sulfoxide. For example, 2,3-dihydrobenzo[6]thiepin is formed in 81% yield from 2,3,4,5-tetrahydrobenzo[Z>]thiepin-5-ol in 4-8 molar equivalents of dimethyl sulfoxide 35... 

Acid-catalysed addition of primary, secondary, and tertiary alcohols to 3,4-dihy-dro-2//-pyran in dichloromethane at room temperature is the only general method currently in use for preparing THP ethers and the variations cited below concern the choice of acid. The reaction proceeds by protonation of the enol ether carbon to generate a highly electrophilic oxonium ion which is then attacked by the alcohol. Yields are generally good. Favoured acid catalysts include p-toluenesulfonic acid or camphorsulfonic acid. To protect tertiary allylic alcohols and sensitive functional groups such as epoxides, the milder acid pyridinium p-toluenesulfonate has been employed (Scheme 4.316]. A variety of other acid catalysts have been used such as phosphorus oxychloride, iodotrimethylsilane- and bis(trimethylsilyl)sulfate. but one cannot help but suspect that in all of these cases, the real catalyst is a proton derived from reaction of the putative catalysts with adventitious water. Scheme 4.317 illustrates the use of bis(trimethylsilyl)sulfate in circumstances where other traditional methods failed. - For the protection of tertiary benzylic alcohols, a transition metal catalyst, [Ru(MeCN)2(triphos)](OTf)2 (0.05 mol%) in dichloromethane at room temperature is effective. ... 

Alkylation of Nitrile Derivatives. Tertiary benzylic nitriles were prepared from aryl fluorides and secondary nitrile anion. In the presence of 4 equiv of nitrile and 1.5 equiv of a base, the nucleophilic aromatic substitution of fluoroarenes led to tertiary benzylic nitriles (eq 36). KHMDS was the best base for this reaction, as LiHMDS and NaHMDS provided lower yields. The desired product was not observed when CS2CO3, LDA, or f-BuOK were used. "With KHMDS, the reaction proceeded in high yields with a variety of substrates. 

A plausible explanation for the observed regiochemical outcome may involve preliminary transformation of the putative laterally hthiated aryltetrahydrofuran 125 into the reactive o-quinone dimethide alkoxide derivative 126 (2011AGE6906). This 1,4-elimination product 126 may then undergo a nucleophilic conjugate addition by a second equivalent of base to give the tertiary benzylic carbanion 127. This is finally intercepted by the electrophile (if any) to furnish adduct 128 after acid quenching at room temperature (Scheme 35). 

The intramolecular Schmidt reactions of azido tertiary benzylic and propargylic alcohols 32 lead to l-azabicyclo[5.3.0]decanes or 1-azabicyclo[4.3.0]decanes (indolizidines) 36 without formation of the products derived from cation rearrangement. However, simple tertiary alcohols such as 37 undergo cation rearrangement prior to cyclization to give a mixture of regioisomeric indolizidines. 

Recently, Ackermann and coworkers reported aliphatic hydroxyl-directed oxidative annulation reactions of benzyl alcohols with alkynes to form isochromene derivatives (Eq. (7.11)) [16]. This C-H/O-H functionalization process performed smoothly by using [RuCl2(/ -cymene)]2 (5 mol%)/AgPFg (20 mol%) as catalyst and Cu(OAc)2 H2O (20 mol%) as oxidant under an atmosphere of air. Various tertiary benzylic alcohols, a,a-dimethylallyl alcohol, and diverse internal alkynes are appropriate substrates for this transformation. The reaction occurred with moderate to high regioselectivity for unsymmetrical alkylarylacetylene, and an irreversible C-H metalation step is involved in the catalytic cycle. 

Rueping et al. also developed separate conditions for the addition of phosphates, cyanide, and acetylides. Cyanations (or Strecker-type reactions) of THIQ derivatives were achieved using Ir(tbppy)2(bpy)PF6 (tbppy=2-(4-rert-bu1yl-phenyl)-pyridine 4) in acetonitrile and tertiary benzylic amines with potassium cyanide, in which the addition of acetic acid was crucial for HCN liberation and solubility. Product yields range from 81-97% (Scheme 10.7). In addition to THIQ derivatives, substituted anilines also underwent coupling, with allq l C-H bonds oxidized in preference to benzylic C-H bonds. 

Esters derived from the primary alcohols are the most stable and those derived from the tertiary alcohols are the least stable. The decomposition temperature is lower in polar solvents, eg, dimethyl sulfoxide (DMSO), with decomposition occurring at 20°C for esters derived from the tertiary alcohols (38). Esters of benzyl xanthic acid yield stilbenes on heating, and those from neopentyl alcohols thermally rearrange to the corresponding dithiol esters (39,40). The dialkyl xanthate esters catalytically rearrange to the dithiol esters with conventional Lewis acids or trifluoroacetic acid (41,42). The esters are also catalytically rearranged to the dithiolesters by pyridine Ai-oxide catalysts (43) ... 

Treatment of a tertiary benzylamine also affords the Troc derivative with cleavage of the benzyl group (CI3CCH2OCOCI, CH3CN, 93% yield). ... 

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