Chloro titanium

The highly regio- and diastereoselective addition of an alkyl and an arylthio group to an olefinic double bond ( carbosulfenylation ) is achieved with arenesulfenyl chlorides and alkyl-chloro-titanium(IV) species (Reetz reagent, from R2Zn/TiCU 5 1 M. T. Reetz, 1987, 1989), Use of the more bulky 2,4,6-triisopropylbenzenesulfenyl chloride improves the yield of the highly versatile alkyl aryl sulfide products. 

Titanium enolates of various carbonyl compounds play an increasingly important role in Mannich-type reactions with different electrophiles. Recently, Liotta and co-workers reported a novel diastereoselective addition of chloro-titanium enolate 80 of iV-acylthiazolidinethione to various types of O-methyl oximes to afford the desired anti-azetines, precursors of a,/3-disubstituted /3-amino carbonyl derivatives 82 (Scheme 32).109... 

Mono-Cp chloro titanium complexes containing a sulfide-bridged chelating bis(aryloxo) ligand have been synthesized and characterized (Scheme 383). The complex Ti(tbmp)Gl2 reacts with LiCp (Cp =Cp, Cp, G5H4SiMe3) to... 

Allyltitanium compounds and Ti enolates derived from mono-Gp chloro titanium complexes with two chiral alkoxo ligands add to aldehydes with high enantioface discrimination.973... 

CpTiCl3 reacts with sodium salts of ferrocenylcarboxylates to afford biferrocenylcarboxylato derivatives of mono-Gp chloro titanium(iv) which show monodentate carboxylate bonding.1768,1769... 

Chiral, Nonraeemic Trialkoxy(chloro)titanium Complexes29 ... 

The in situ prepared trialkoxy(chloro)titanium complex is dissolved in CH2C1, (ca. 5 mL per mmol). At -30CC ca. 0.8 equiv of methyl acrylate (5), and after 30 min at the same temperature ca. 2 3 equiv of cyclopcntadiene, are added dropwise. The mixture is kept overnight (ca. 15 h) at - 30 =C, then hydrolyzed with ca. 20 niL of 2 N HC1 and extracted with Ft20. When (R)-binaphthol (7) is used it is extracted with 2 N NaOH. In the case of the 1.3-dioxolanc derivatives it is precipitated by the addition of pentane to the crude reaction mixture, then filtered off. The crude product is purified by flash chromatography. For determination of the oplical rotation a sample is purified by Kugclrohr distillation (130 fC/l 5 Torr). When (3 )-binaphthol (7) is used the adduct is obtained in 77% yield with 50% cc of the (-)-(f )-enantiomer. With the (R.R)-diol 8 derived from tartrate, the (-)-(S)-adduct is predominant (55% yield) with 46% ee. 

The six coordinated titanium(IV) compounds, Ti(acac)2(X)2, where X is methoxy, ethoxy, isopropoxy, -butoxy, or chloro, all adopt the cis-configuration. This is beheved to result from the ligand-to-metal TT-electron donation (88,89). 

Acylates. Titanium acylates are prepared either from TiCl or tetraalkyl titanates. Because it is difficult to obtain titanium tetraacylates, most compounds reported are either chloro- or alkoxyacylates. Under most conditions, TiCl and acetic acid give dichlorotitanium diacetate [4644-35-3]. The best method iavolves passiag preheated (136—170°C) TiCl and acetic acid simultaneously iato a heated chamber. The product separates as an HCl-free white powder (125) ... 

Chloro-tri-isopropyl titanium [20717-86-6] M 260.6, m 45-50 , b 61-65 /0.1mm. Distd under vacuum and sets slowly to a solid on standing. Stock reagents are made by dissolving the warm liquid in pentane, toluene, Et20, THE, CH2CI2, and can be stored in pure state or in soln under dry N2 for several months. The reagent is hygroscopic and is hydrolysed by H2O. [Chem Ber 118 1421 1985.]... 

A one-step transformation of the C5-OH in 86 to the 5-(piperid-l-y)- or 5-(morpholin-4-yl) derivatives 168 was carried out by heating with the respective amines 166 in the presence of titanium tetrachloride. Tlie reaction probably involved formation of the unisolable 5-chloro compounds 167 (93JHC11) (Scheme 64). 

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). 

A synthetically useful diastereoselectivity (90% dc) was observed with the addition of methyl-magnesium bromide to a-epoxy aldehyde 25 in the presence of titanium(IV) chloride60. After treatment of the crude product with sodium hydride, the yy -epoxy alcohol 26 was obtained in 40% yield. The yyn-product corresponds to a chelation-controlled attack of 25 by the nucleophile. Isolation of compound 28, however, reveals that the addition reaction proceeds via a regioselective ring-opening of the epoxide, which affords the titanium-complexed chloro-hydrin 27. Chelation-controlled attack of 27 by the nucleophile leads to the -syn-diastereomer 28, which is converted to the epoxy alcohol 26 by treatment with sodium hydride. 

A more effective control of both simple diastereoselectivity and induced stereoselectivity is provided by the titanium enolate generated in situ by transmetalation of deprotonated 2,6-dimethylphenyl propanoate with chloro(cyclopentadienyl)bis(l,2 5,6-di-0-isopropylidene-a-D-glucofuranos-3-0-yl)titanium. Reaction of this titanium enolate with aldehydes yields predominantly the. yyw-adducts (syn/anti 89 11 to 97 3). The chemical yields of the adducts are 24 87% while the n-u-products have 93 to 98% ee62. 

Carbohydrate-derived titanium cnolates also provide yvn-x-amino-/l-hydroxy esters of high diastcrcomeric and enantiomeric purity. For this purpose, the lithium enolate derived from ethyl (2,2,5,5-tetramcthyl-2,5-disilapyrrolidin-l-yl)acetate is first transmctalated with chloro(cy-clopentadienyl)bis(1,2 5,6-di-0-isopropylidene-a-D-glucofuranos-3-0-yl)titanium and subsequently reacted with aldehydes.. vj-n-a-Amino-/ -hydroxy esters are almost exclusively obtained via a predominant /te-side attack (synjanti 92 8 to 96 4 87-98% ee for the xvn-adducts)623-b. 

In another approach, a glucose-derived titanium enolate is used in order to accomplish stereoselective aldol additions. Again the chiral information lies in the metallic portion of the enolate. Thus, the lithiated /m-butyl acetate is transmetalated with chloro(cyclopentadienyl)bis(l,2 5,6-di-0-isopropylidene- -D-glucofuranos-3-0-yl)titanium (see Section I.3.4.2.2.I. and 1.3.4.2.2.2.). The titanium enolate 5 is reacted in situ with aldehydes to provide, after hydrolysis, /i-hydroxy-carboxylic acids with 90 95% ee and the chiral auxiliary reagent can be recovered76. 

On the other hand, when this lithium enolate is transmetalated with 3 equivalents of chloro-(triisopropyloxy)titanium, the induced stereoselectivity is inverted to give a 25 75 ratio of adducts. 

Allylic silanes react with dichlorocarbenes, generated from dechlorination of carbon tetrachloride with low valent titanium species, to furnish dichlorocyclopropanes, which in turn get desilylated with CsF in DMF to generate 3-chloro-l,3-butadienes (equation 30)63. 

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-trialkylated ethylenes in the presence of titanium tetrachloride35. Because of the low S/v 1 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 BCI3. Under these conditions, the intermediate 46 could be trapped by Cl since BCI4 is more nucleophilic than TiC.15 (equation 16). 

Covalently bonded chiral auxiliaries readily induce high stereoselectivity for propionate enolates, while the case of acetate enolates has proved to be difficult. Alkylation of carbonyl compound with a novel cyclopentadienyl titanium carbohydrate complex has been found to give high stereoselectivity,44 and a variety of ft-hydroxyl carboxylic acids are accessible with 90-95% optical yields. This compound was also tested in enantioselective aldol reactions. Transmetalation of the relatively stable lithium enolate of t-butyl acetate with chloro(cyclopentadienyl)-bis(l,2 5,6-di-<9-isopropylidene-a-D-glucofuranose-3-0-yl)titanate provided the titanium enolate 66. Reaction of 66 with aldehydes gave -hydroxy esters in high ee (Scheme 3-23). 

The phthalic anhydride/urea process may also be employed to convert tetra-chloro phthalic anhydride to green copper hexadecachloro phthalocyanine by condensation. In this case, titanium or zirconium dioxides, particularly in the form of hydrated gels, are used instead of the molybdenum salts which are used in the phthalic anhydride process [23]. There is a certain disadvantage to the fact that the products lack brilliance and require additional purification. 

Oki and his co-workers (177) also found that these halogenated compounds (107) exhibited enormous differences in reactivity when they were treated with Lewis acids. The sc form undergoes a Friedel-Crafts type cyclization in the presence of titanium tetrachloride, which is a weak Lewis acid, whereas the ap form survives these conditions. The latter reacts in the presence of the stronger Lewis acid antimony pentachloride. This difference is apparently caused by a chloro group in proximity to the site where a cationic center develops during the reaction (Scheme 12). 

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