Titanium tetrachloride 2+2 -cycloadditions

Engler and colleagues256 demonstrated that the way in which catalyst 406 is prepared has a strong effect on the regioselectivity and enantioselectivity of quinone Diels-Alder reactions. The most effective catalyst was prepared from a 1 1 1 mixture of titanium tetrachloride, titanium tetraisopropoxide and chiral diol 416. The cycloadditions of 2-methoxy-l,4-benzoquinones such as 414 with simple dienes to give adducts like 415 proceeded with high yields and enantioselectivities of up to 80% ee using this catalytic system (equation 123). 

Monochlorotitanium complex 418, prepared from (l/J,25 )-Af-(2,4,6-trimethylbenze-nesulfonyl)-2-amino-l-indanol and titanium tetraisopropoxide followed by treatment with titanium tetrachloride effectively catalyzed the cycloaddition of a-bromoacrolein to cyclo-pentadiene, affording 366 with 93% ee (equation 125)259. Catalyst 418 induced an ee of 90% in the reaction of isoprene with a-bromoacrolein. 

The first recorded cyclopropyl acyl silane (69) was generated by vapour phase pyrolysis of a pyrazoline derived from a,/)-unsaturated acyl silane by 1,3-dipolar cycloaddition of diazomethane (vide supra, Section DTE)141. Exposure of 69 to titanium tetrachloride induced ring expansion to give the cyclobutanone in 75% yield (Scheme 113). 

The method of formation of complicated polycyclic compounds by an intramolecular cycloaddition in 1,4-dihydropyridines containing ortho-aikcny-laryl substituents is very common and is also observed in many other cases. For instance, treatment of dihydropyridines 361 with titanium tetrachloride in... 

Table 8 Diastereoselection in Cycloadditions Promoted by Titanium Tetrachloride...

Titanium Lewis acids effect formal [2 + 2] cycloaddition as shown in Eqs (158) [401] and (159) [402,403]. Subtly changing the reaction conditions and substrates alters the product of Eq. (159) from the cyclobutane to a dihydrobenzofuran derivative, as will be described below. The analogous hetero [2 + 2] addition of a chiral aldehyde to a silylketene proceeded stereoselectively in the presence of titanium tetrachloride to give the propiolactone, as shown in Eq. (160) [404]. The silyl group was removed by the treatment with KF. 

Highly alkylated l-chloro-2-(trimethylsilyl)cyclopentenes 44, which are of interest as possible cyclopentyne precursors, were prepared by reacting 3-chloro-3-methyl-l-(trimethylsilyl)but-l-yne (45) with 1,1-dialkylated or 1,1,2-triaIkylated ethylenes in the presence of titanium tetrachloride. Because of the low S l reactivity of 45, the yields of the products were moderate. The stepwise [3 + 2]-cycloaddition mechanism discussed above was proven by the isolation of the intermediate acyclic adduct (in 74% yield) when 45 and isobutene were reacted in the presence of BCR, Under these conditions, the intermediate 46 could be trapped by Cl since BCU is more nucleophilic than TiCls" (equation 16). 

The regio- and stereo.selective 2 + 2 cycloaddition of phenylacetylene to the allene 147 results in the (Z)-cyclohutenylideneoxazolidin-2-one 148 similarly, methyl acrylate affords the analogue 149 <97JA10869>. The dimetliyleneoxazolidinone 150 adds methyl vinyl ketone in the presence of aluminium trichloride or titanium tetrachloride to yield mainly the endo Diels-Alder adduct 151 <97JOC4103>. 

The diacetylene 15 readily underwent Diels-Alder cycloaddition with furan to furnish the endoxide 16, which was hydrogenated catalytically to the tetrahydro compound 17. Dehydration of 77 with polyphosphoric acid gave 1 in 16% yield (Eq. 7) Alternatively, deoxy nation of 16 with low valent titanium generated by reducing titanium tetrachloride with lithium aluminium hydride also afforded 7 in 50% yield... 

The first example of supported titanium-catalysed DA reaction was reported by Luis et al. in 1992 (Scheme 7.49). In this work, the authors described the preparation of several polymeric alcohols derived from Merrifield resin and their efficiency as ligand in titanium-catalysed cycloaddition between methacrolein and cyclopentadiene with yields between 83-99% and good exo selectivity. With the aim to evaluate the enantioselectivity of the reaction, catalyst 80 was then prepared almost quantitatively by double esterification of tartaric acid with chloromethylated polystyrene and a 1 1 mixture of titanium tetrachloride/titanium tetraisopropoxide. " Despite the good conversion and selectivity toward the exo-cycloadduct, only 3% enantiomeric excess was recorded, which was attributed to the very high reactivity of the system. Recycling of the catalyst was successfully performed by filtration from the reaction media and washing with dichloromethane, and catalyst 80 was reused seven times without significant loss of catalytic activity. 

In previous investigations we could show that carbohydrate enones with the electrophilic terminus of the unsaturated carbonyl system at the anomeric carbon react with silyl enol ethers under catalysis of titanium tetrachloride, i. e. in a Mukaiyama-type reaction, to give the corresponding C-glycosides in high diastereoselectivity. The high stereocontrol observed could be explained in terms of a strongly adjusted cycloaddition-like transition state. This... 

Compared to the relatively young history of the pure metal, aluminium compounds have been known for ages from the above-cited alum class to the more exclusive transition metal-doped aluminium oxides like ruby and sapphire (corundum varieties with chromium for the former and titanium and iron impurities for the latter) or aluminosilicate-like emeralds (a beryl type with chromium and vanadium impurities). However, to the synthetic chemist, aluminium chloride, is de facto one of the first jewels of the aluminium family. Aluminium trichloride (together with titanium tetrachloride, tin tetrachloride and boron trifluoride) is an exemplary Lewis acid that finds many applications in organic synthesis It is extensively used for instance in Friedel-Crafts alkylations and acylations, in Diels-Alder-type cycloadditions and polymerisation reactions. Its involvement in a wide range of reactions has been documented in many reviews and book chapters. ... 

A suggestion has been made that asymmetric induction is possible in cycloaddition reactions leading to azetidinones. The reaction of dimethylketene methyl-trimethylsilylacetal with the Schifl s bases of chiral a-aminoesters in the presence of titanium tetrachloride gave rise to the corresponding /3-lactams with extremely high stereoselectivity. The authors propose the formation of a template (183) between titanium and the Schiff s base leading to stereocontrol (Scheme 24). 

The synthesis of tricyclic compound 120 was first reported by Tamura and co-workers using a tandem transesterification-cycloaddition reaction of nitrone methyl ester 118 and cyclohexen-3-ol (Scheme 16.17). This reaction was catalyzed by titanium tetrachloride to make nitrone cyclohexenyl ester 119. A subsequent 1,3-dipolar cycloaddition reaction proceeded presumably through a transition state involving the i-cis-like conformation of the ester C—O bond and the E configuration of the nitrone C=N bond (Scheme 16.17). 

The (-l-)-piperazic acid trifluoroacetate salt 208 was obtained from the cycloaddition of 4-phenyltriazoline-3,5-dione 204 with chiral diene 205 by Hamada and co-workers (Scheme 41.44). The reaction between the diene and the dienophile from —78°C to room temperature in dichloro-methane without additives afforded a 1 1 mixture of diaster-eomers. The use of 0.5 equivalents of titanium tetrachloride pleasingly resulted in an increase of the ratio to 84 16 in favor of 206a. After optimization, it was found that with 3 equivalents of the Lewis acid, the diastereoselectivity reached a 97 3 ratio in 95% yield. T vo equivalents of TiCLi are chelated by the two carbonyls of the dienophile, whereas 1 equivalent serves as the chelator between the two carbonyl functions in the chiral diene. The major conformer 207a that precluded the A strain is then engaged in a e cycloaddition with the azo compound opposite to the face of the chiral auxiliary s benzyl group. 

Makino K, Henmi Y, Terasawa M, Hara O, Hamada Y. Remarkable effects of titanium tetrachloride in diastereoselective aza Diels-Alder cycloaddition synthesis of (S)-piper-azic acid. Tetrahedron Lett. 2005 46 555-558. 

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