Titanium benzylidene

In the indole synthesis, the authors reported the necessity to avoid protons during the titanium benzylidene formation prior to the capping with the support-bound ester. It was found fhat fhe possibility of proton transfer in this stage of fhe reaction would lead to an exhaustive reduction of fhe difhioacetal function to a mefhyl group. Thus, fhe orfho-nucleophile (Boc-NH-functions) had to be protected by silylation. 

Additionally, it has been shown that novel benzylidene titanium complexes of type 74 react with polymer-bound carboxylic esters to form the corresponding enol ethers (Scheme 28).79... 

Scheme 11.45 shows a proposal for the transition state involved in a related Lewis acid catalyzed cycloaddition where a disubstituted dipolarophile is used and endo/exo issues are examined. By coordination of the bulky titanium Lewis acid catalyst, the a-carbon of the acceptor becomes sterically more hindered, disfavoring exo-approach, which involves a serious steric interaction of the benzylidene phenyl moiety with the ligands on the titanium ion. Accordingly, the endo-cycloadduct is the only product observed. 

Titanium(iv) benzylidenes (Schlock carbenes) 4 react with resin-bound esters 5 to generate the resin-bound enol ethers 6. Treatment of the enol ethers with a mixture of trifiuoroacetic acid (TEA) and trifluoroacetic anhydride (TFAA) leads to cleavage from the resin, removal of the Bu Me2Si group, and subsequent cyclization to give the benzothiophenes 7 (Scheme 2) <2004JOC6145>. 

During their synthesis of the Dactomelynes, Lee and co-workers employed sodium cyanoborohydride and titanium(IV) chloride95 to accomplish the regiose-lective cleavage of a benzylidene acetal [Scheme 3,57].%... 

Trost first introduced the di-fe/7-butylsilylene derivative as a means for protecting 1,2- and 1,3-diols during a synthesis of PiUaromycinone derivatives.213 Di-ferf-butylsilylene derivatives are not as robust as isopropylidene or benzylidene acetals and their use is best reserved for systems requiring deprotection under very mild conditions. Di-isopropylsiiylene derivatives are occasionally used but they usually only survive in highly crowded environments.214 Di-feri-butylsily-lene derivatives survive hydroboration with 9-BBN, mild oxidation (e g the Dess-Martin, ozone), Lewis acids such as trifluoroborane e the rate and titanium tetrachloride, mild acids (pyridinium p-toluenesulfonate). camphorsulfonic acid, strong bases such as feri-butyllithium (THF, -50 °C), DDQ, and sodium meth-oxide in methanol at 0 C — conditions used to cleave acetate esters. 

Ally) ethers are selectively cleaved with titanium(lV) isopropoxide and commercially available Grignard reagents like /i-butyl- or cyclohexylmagnesium chloride [Scheme 4.229].432 Neither benzylidene acetals nor more highly substituted allylic ethers suffer under the reaction conditions. A mechanism for the reaction implicates formation of the titanacyclopropane intermediate 229.1 as the first step. Ligand exchange with an unsubstituted allyl ether affords intermediate 229.2. -Elimination to the allyltitanium(lV) alkoxide 2293 followed by hydrolysis returns the deprotected alcohol. The reaction closely resembles an earlier method based on zirconium.433... 

Other adducts with neutral O-donor ligands include TiCl4,OP(OEt)3 TiCl4,L2 (L = difurfurylidene cyclopentanone, difurfurylidene cyclohexanone, di-benzylidene cyclopentanone, or dibenzylidene cyclohexanone) titanium compounds with some 0-containing organic compounds. 

Scheme 28) <92JHC25l>. Unsaturated 5(4//)-oxazolones also serve as dienophiles. The (Z) isomer of 2-phenyl-4-benzylidene-5(4//)-oxazolone reacts with cyclopentadiene in the presence of aluminum chloride or titanium tetrachloride to afford a mixture of exo and endo cycloadducts <90S1114>. 

Treatment of Y -(benzylidene)benzohydrazonoyl chlorides 38 with titanium tetrachloride in chloroform produced symmetrically substituted 3,6-diaryl-l,4-dihydro-l,2,4,5-tetrazines 2 in moderate yields. The authors suggest that cyclocondensation between two molecules of hydrazonoyl chloride takes place first, followed by elimination of two molecules of an aldehyde during hydrolytic workup. Oxidation of the dihydrotetrazines 2 with nitrous acid afforded the fully conjugated tetrazines 1 in 32-56% yields (Scheme 8) <2000MI37>. 

Tetrachloro(o-[N-2-pyridylformimidoyl)phenol) Titanium Tetrachloro(4-([p-(Dimethylamino)benzylidene)amino) -pyridinejtitanium... 

Related C-H activations by 1,2-additions across metal-ligand bonds have also been reported with unusual group 4 alkylidyne complexes. - As shown in Equation 6.58, a titanium(IV) trimethylsilylmethyl benzylidene complex eliminates tetramethylsilane to generate a Ti(IV) alkylidyne complex. This complex then reacts with benzene to add the arene C-H bond across the metal-alkylidyne unit to form an aryl benzylidene complex. 

Condensation of 2,3 4,5-di-O-benzylidene-D-ribose or related aldehydo-D-ribose or -D-glucose derivatives with a number of active methylene compounds, e.g., pentane-2,4-dione, gave the expected Knoevenagel condensation products, which all showed antiviral activity and cytotoxicity the most effective against herpes simplex virus was the ribose-2,4-pentanedione derivative (34) titanium... 

Protection of D-erythrono-1,4-lactone as its 2,3-0-benzylidene acetal, followed by regioselective reductive acetal opening (triethylsilane-titanium tetrachloride), then hydride reduction of the lactone function gave 2-0-benzyl-L-erythritol. In contrast, tributyltin oxide mediated benzylation of the same 1,4-lactone then hydride reduction of the lactone group gave 2-0-benzyl-D-erythritol. L-Erythrulose has been converted into 2-amino-2-deoxy-L-erythritol in six steps and 35% overall yield, the key step being a stereoselective reduction of the ketoxime orthoformate 11 with K-selectride. ... 

Titanium(IV) benzylidenes bearing a masked oxygen or nitrogen nucleophile can be used in the synthesis of benzofurans and indoles. Macleod... 

There are several nonpyrolytic methods of obtaining spherical surfaces. These include titanium-, vanadium-, and nickel-mediated reductive coupling of benzyl and benzylidene bromides, intramolecular carbenoid coupling of dibromomethyl groups, and Pd-catalyzed intramolecular arylation with aryl halides [291]. 

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