Titanium catalyzed

For the construction of oxygen-functionalized Diels-Alder products, Narasaka and coworkers employed the 3-borylpropenoic acid derivative in place of 3-(3-acet-oxypropenoyl)oxazolidinone, which is a poor dienophile in the chiral titanium-catalyzed reaction (Scheme 1.55, Table 1.24). 3-(3-Borylpropenoyl)oxazolidinones react smoothly with acyclic dienes to give the cycloadducts in high optical purity [43]. The boryl group was converted to an hydroxyl group stereospecifically by oxidation, and the alcohol obtained was used as the key intermediate in a total synthesis of (-i-)-paniculide A [44] (Scheme 1.56). 

A chiral titanium complex with 3-cinnamoyl-l,3-oxazolidin-2-one was isolated by Jagensen et al. from a mixture of TiCl 2(0-i-Pr)2 with (2R,31 )-2,3-0-isopropyli-dene-l,l,4,4-tetraphenyl-l,2,3,4-butanetetrol, which is an isopropylidene acetal analog of Narasaka s TADDOL [48]. The structure of this complex was determined by X-ray structure analysis. It has the isopropylidene diol and the cinnamoyloxazolidi-none in the equatorial plane, with the two chloride ligands in apical (trans) position as depicted in the structure A, It seems from this structure that a pseudo-axial phenyl group of the chiral ligand seems to block one face of the coordinated cinnamoyloxazolidinone. On the other hand, after an NMR study of the complex in solution, Di Mare et al, and Seebach et al, reported that the above trans di-chloro complex A is a major component in the solution but went on to propose another minor complex B, with the two chlorides cis to each other, as the most reactive intermediate in this chiral titanium-catalyzed reaction [41b, 49], It has not yet been clearly confirmed whether or not the trans and/or the cis complex are real reactive intermediates (Scheme 1.60). 

Figure 6.3 Diastereofacial differentiation in titanium-catalyzed AE of secondary allylic alcohols.

The titanium-catalyzed AE reaction is a fairly robust system and it can be performed on substrates containing a wide range of different functional groups (FGs) (Table 6.3) [13]. However, it is important to point out that an intramolecular reaction with the formed epoxide is possible whenever the FG present in the molecule has a favorable position to facilitate such a transformation. An illustration of this phenomenon is presented in Eq. (1) [28]. 

Table 6.3 Functional group tolerance in the titanium-catalyzed AE reaction.

While the titanium-catalyzed epoxidation reaction was flourishing, the pioneer version of the reaction remained undeveloped and it was not until 1999 that new... 

Salen ligands have also been used in the titanium-catalyzed trimethylsilyl-cyanation of benzaldehyde. The complexes were immobilized by substitution of a chloride with a surface silanol from the support. In the first study on this reaction [38], the most efficient ligand was the non-symmetrical salen Im (Fig. 11) (94% ee), whereas the selectivity obtained with the symmetrical ligand la was significantly lower (72% ee). In a recent paper, the immobilization of different titanium species, including monomeric and dimeric systems with... 

Clerici and Porta reported that phenyl, acetyl and methyl radicals add to the Ca atom of the iminium ion, PhN+Me=CHMe, formed in situ by the titanium-catalyzed condensation of /V-methylanilinc with acetaldehyde to give PhNMeCHMePh, PhNMeCHMeAc, and PhNMeCHMe2 in 80% overall yield.83 Recently, Miyabe and co-workers studied the addition of various alkyl radicals to imine derivatives. Alkyl radicals generated from alkyl iodide and triethylborane were added to imine derivatives such as oxime ethers, hydrazones, and nitrones in an aqueous medium.84 The reaction also proceeds on solid support.85 A-sulfonylimines are also effective under such reaction conditions.86 Indium is also effective as the mediator (Eq. 11.49).87 A tandem radical addition-cyclization reaction of oxime ether and hydrazone was also developed (Eq. 11.50).88 Li and co-workers reported the synthesis of a-amino acid derivatives and amines via the addition of simple alkyl halides to imines and enamides mediated by zinc in water (Eq. 11.51).89 The zinc-mediated radical reaction of the hydrazone bearing a chiral camphorsultam provided the corresponding alkylated products with good diastereoselectivities that can be converted into enantiomerically pure a-amino acids (Eq. 11.52).90... 

The chiral diol 17 derived from tartaric acid is exploited in the titanium-catalyzed asymmetric pinacol coupling in the presence of Zn and MesSiCl to give the corresponding diol in 11-71 ee % [44], The chiral salen ligands 18-20 are used in the titanium-catalyzed enantioselective coupling reaction, which achieves the higher selectivity [45-47]. The chromium complex with TBOxH (21) efficiently catalyzes the asymmetric coupling reaction of both aromatic and aliphatic aldehydes [48]. 

A similar dichotomy was observed in the titanium catalyzed polymerization of primary silanes coupled to the hydrogenation of norbornene (20). At low catalyst concentration (ca. 0.004H), essentially complete conversion of norbornene to an equimolar mixture of norbornane and bis-phenylsilyl- (and/or 1,2-diphenyl-disilyl)norbornane was observed. Under these conditions no evidence for reduction of titanium was obtained. At higher catalyst concentrations (> 0.02M) rapid reduction of the dimethyltitanocene to J, and 2 occurs and the catalytic reaction produces mainly polysilane (DPn ca. 10) and norbornane in ca. 80 per cent yields, and silylated norbornanes in about 20 per cent yield. 

Beller and coworkers [312] have recently published a very useful domino reaction using a Ti-based Lewis acid as catalyst to prepare indoles. The new procedure consists of a titanium-catalyzed amination of a chloroalkylalkyne to give an aryl hydra-... 

The key step in the synthesis of A-ring fragment 50 [56] is the chelation-controlled addition of allylstannane 53 to aldehyde 52, which sets the C7 stereocenter and introduces the C8 gem-dimethyl moiety. Aldehyde 52 is itself prepared from 1,3-propanediol using the author s protocol for titanium-catalyzed enantioselective allylstannation [57], which sets the C5 stereocenter, followed by chelation-controlled Mukaiyama aldol addition [58] to establish the C3 stereocenter (Scheme 5.6). 

Computational results showed that activation barriers for the aromatization process are always lower for aluminum-catalyzed reactions and, similarly, lower for titanium-catalyzed than for zinc-catalyzed reactions [52]. 

Balema, V.P., J.W. Wiench, K.W.M. Dennis, M. Pruski, and V.K. Pecharsky, Titanium catalyzed solid-state transformations in LiAlH4 during high-energy ball-milling, /. Alloys Compd., 329, 108, 2001. 

The chemistry of titanium has been reviewed in COMC (1982) and COMC (1995)40 41 as well as in Comprehensive Coordination Chemistry II. 2 Since then, several contributions have covered the coordination chemistry of cyclopenta-dienyltitanium carboxylates and related complexes,43 new titanium imido chemistry,44 the use of titanium(iv) chloride45 and isopropoxide46 in stereoselective synthesis, the preparation and synthetic applications of l, -dicarba-nionic titanium intermediates47 and organotitanium complexes,48 49 and titanium-catalyzed enantioselective... 

Finally, Odom and co-workers reported a titanium-catalyzed three-component coupling between primary amines, alkynes, and isonitriles for the preparation of a, 3-unsaturatcd /3-iminoamines in good yields (Scheme 35).121 Beside the three-component coupling product, an. V,.V-disubstituted formamidine and an imine were also identified as minor... 

Based on the established mechanism for titanium-catalyzed hydroamination, the authors propose a reversible reaction between a titanium imide complex and the alkyne to form metalloazacyclobutene 86, which in turn undergoes 1,1-insertion of the isonitrile into the Ti-C bond. The generated five-membered ring iminoacyl-amido complex 87 with the new C-C bond is protonated by the primary amine to afford the desired three-component coupling product, with regeneration of the catalytic imidotitanium species. Very recently, titanium-catalyzed carbon-carbon bond-forming reactions have been reviewed.122... 

For a review encompassing titanium-catalyzed hydrosilylation of alkenes and carbonyl compounds, see Harrod, J. F. Coord. Chem. Rev. 2000, 206-207, 493-531. 

Buchwald and co-workers56 found that ( )-olefins cycloisomerized upon exposure to [Cp2Ti(GO)2] giving exclusively the 1,4-diene Alder-ene products (Equation (46)). In contrast to the palladium conditions developed by Trost (see Section 10.12.4.1), the 1,4-diene is formed exclusively, even from substrates containing a tertiary carbon at the allylic position 75. It was noted, however, that heating the reaction mixture for an extended period of time in some instances led to olefin isomerization, forming 1,3-dienes. The mechanism of this titanium-catalyzed... 

This approach provides a new method for carbohydrate synthesis. In the synthesis of tetritols, pentitols, and hexitols, for example, titanium-catalyzed asymmetric epoxidation and the subsequent ring opening of the thus formed 2,3-epoxy alcohols can play an essential role. 

Particularly noteworthy is the discovery of a new type of the active catalyst 99,103,104 a crystalline, air-stable yellow-orange solid, which can serve as a highly enantioselective tool in the titanium-catalyzed hydrosilylation of imines. The reaction can be highly stereoselective for both acyclic and cyclic imines under a wide range of hydrogen pressures (Scheme 6-46). 

Figure 2.7 Mechanism for the titanium-catalyzed transesterification in PET, as proposed by Weingart [39]...

Finally, it has been reported that the titanium-catalyzed (TiCl4/Et2AlCl) cyclotrimerization of l-phenyl-2-(trimethylsilyl)acetylene affords the ter-phenyl silane l,3,5-triphenyl-2,4,6-tris(trimethylsilyl)benzene in trace amounts.101... 

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