Unsaturated carbonyl compounds titanium

An alternative procedure, which was devised for the synthesis of heteroannulated chromenes, involves the reaction of the titanium salt of the phenol with an a, 3-unsaturated carbonyl compound. " This is illustrated for the reaction of iV-methyl-3-hydroxycarbazole (1.26) with P-phenylcinnamaldehyde, which produces the carbazolopyran (1.27) in 35% yield. ... 

Aldehydes 39a-g — 54 react smoothly with methyltitanium triisopropoxide 6 (the numbers in parentheses refer to yields of isolated adducts). Generally, a 10-15% excess of titanium reagent is used, except in compounds containing HO-groups (100% excess). In case of a, P-unsaturated carbonyl compounds, the 1,2-addition mode is observed 22,76,82). 

As previously mentioned, 1-alkynyltrialkylborates (18) have become increasingly important in the formation of carbon-carbon bonds via attack of electrophiles. However, such complexes cannot react with simple Qc,P-unsaturated carbonyl compounds such as methyl vinyl ketone, because of their weak electrophilicity. Recently it was ascertained that ,P-unsaturated carbonyl compounds react with 18 via a Michael-type reaction in the presence of titanium tetrachloride, and the usual alkaline hydrogen peroxide oxidation leads to the synthesis of 5-dicarbonyl compounds... 

Phenylthioalkylation of silyl enol ethers. Silyl enol ethers of ketones, aldehydes, esters, and lactones can be alkylated regiospecifically by a -chloroalkyl phenyl sulfides in fhe presence of a Lewis acid. Zinc bromide and titanium(IV) chloride are the most effective catalysts. The former is more satisfactory for enol ethers derived from esters and lactongs. ZnBr2 and TiCL are about equally satisfactory for enol ethers of ketones. The combination of TiCL and Ti(0-f-Pr)4 is more satisfactory for enol ethers of aldehydes. Since the products can be desulfurized by Raney nickel, this reaction also provides a method for alkylation of carbonyl compounds. Of more interest, sulfoxide elimination provides a useful route to a,B-unsaturated carbonyl compounds. 

Amide Enolates. The lithium (Z)-enolate can be generated from (5)-4-benzyl-3-propanoyl-2,2,5,5-tetra-methyloxazolidine and Lithium Diisopropylamide in THF at —78 °C. Its alkylations take place smoothly in the presence of Hexamethylphosphoric Triamide with high diastereoselec-tivity (eq 3), and its Michael additions to a,(3-unsaturated carbonyl compounds are also exclusively diastereoselective (eq 4). Synthetic applications have been made in the aldol reactions of the titanium (Z)-enolates of a-(alkylideneamino) esters. ... 

If the reaction between enol silyl ethers and a,/ -unsaturated ketones is attempted in the presence of a titanium Lewis acid, the mode of the reaction switches to 1,4-addition with reference to the unsaturated ketone [109-113]. The reaction of an enol silyl ether is shown in Eq. (30) [114]. Ketene silyl acetals react with a,j8-unsaturated ketones in similar 1,4-fashion, as exemplified in Eq. (31) [115]. Acrylic esters, which often tend to polymerize, are also acceptable substrates for a, -unsaturated carbonyl compounds [111]. A difluoroenol silyl ether participated in this cationic reaction (Eq. 32) [116], and an olefinic acetal can be used in place of the parent a-methylene ketone [111] to give the 1,5-diketone in good yield (Eq. 33) [117]. More results from titanium-catalyzed 1,4-addition of enol silyl ethers and silyl ketene acetals to a,f -unsaturated carbonyl compounds are summarized in Table 4. 

The Diels-Alder reaction is one of the most fundamental means of preparing cyclic compounds. Since discovery of the accelerating effect of Lewis acids on the Diels-Alder reaction of a,)3-unsaturated carbonyl compounds [341-344], its broad and fine application under mild reaction conditions has been amplified. Equations (140) [341] and (141) [345], respectively, illustrate typical dramatic effects from an early reaction and from one reported more recently. Lewis acid-promoted Diels-Alder reactions have been reviewed [7,8,346-353]. In addition to the acceleration of the reaction, other important feature is its alteration of chemo-, regio-, and diastereoselectivity this will be discussed below. The titanium compounds used in Diels-Alder reaction are titanium halides (TiX4), alkoxides (Ti(OR)4), or their mixed salts (TiX (OR)4 n = 1-3). A cyclopentadienyl complex such as Cp2Ti(OTf)2 is also documented as a very effective promoter of a Diels-Alder reaction [354], In addition to these titanium salts, a few compounds such as those in Eq. (142) [355] have recently been reported to effect the Diels-Alder reaction. The third, [(/-PrO)2Ti(bpy)(OTf)(i-PrOH)] (OTf), was estimated to be a more active catalyst than Cp2Ti(OTf)2. 

Aziridination of an olefin has been performed with the reagent shown in Eq. (262) in the presence of Ti(0-i-Pr)4 [606,607], Excellent diastereoselectivity was observed. Other methods of aziridination to a, -unsaturated carbonyl compounds [608,609] or of imines [610-612] in the presence of a titanium Lewis acids are also available. 

There are many examples of the stereoselective addition of nucleophiles to carbonyl groups in which chelation to the titanium center should be critical—reported examples include the stereoselective hydride reduction of a- or /3-hydroxyketones (Eq. 305) [684-686], of a-phosphino ketones [687], of a-sulfonylketones [688], and of an a,/3-unsaturated carbonyl compound in a 1,4-fashion [689]. The stereoselective addition of organometallic compounds such as Grignard [669,690], zinc [691,692], copper [693], and other reagents [11] to carbonyl and related compoimds Ijy taking advantage of titanium chelation is a well established method in the stereoselective... 

The reactions of organometallic reagents such as organolithium [696], -zinc [697-700], -magnesium [701], and -aluminum species [702] are facilitated by the presence of TiCU [9] as exemplified in Eq. (308) [703]. Even addition of a titanium compound to aldehydes was promoted in the presence of an extra amount of a titanium salt (Eq. 309) [704,705]. Titanium Lewis acids increase the reactivity of the a-position of a ketone (Eq. 310) [706] and the /3-position of an a,/3-unsaturated carbonyl compound towards nucleophiles (Eq. 311) [608,707-709]. The positive role of TiCU in the photo-hydroxymethylation of ketones and aldimines is ascribed to activation of methanol by the titanium salt (Eq. 312) [710]. 

Na-, La-, and Re-exchanged zeolites have also been used as catalysts of the Michael reaction between silyl enol ethers and a, 6-unsaturated carbonyl compounds. This study, performed by Sasidharan et al. [87], focused mainly on the catalytic activity of titanium silicalite molecular sieves (TS-1 and TS-2). They found that TS-1 and TS-2 catalyze 1,4-Michael addition of silyl enol ethers and a,y5-unsatu-rated carbonyl compounds under anhydrous conditions. The zeolites tested as catalysts of this reaction, e. g. ReY, LaY, steamed zeolite Y, and cation-exchanged ZnZSM-5, were less active (or inactive). 

Spectra.—For compounds of low solubility in deuteriochloroform, the use of ASCI3-CDCI3 (2 1 v/v) may prove valuable as the chemical shift differences (excepting alcohols) between the two solvent systems is negligible (< 1 p.p.m.) on the n.m.r. scale. Titanium tetrachloride-induced shifts on the spectra of carbonyl compounds has been investigated. The carbonyl carbon atoms experience large down-field shifts, adjacent carbon atoms showed only small downfield shifts, and remote carbon atoms are scarcely perturbed. In a -unsaturated carbonyl compounds, large downfield shifts are observed for the P-carbon atoms, presumably because of the enhancement of the dipolar resonance form of the enone system consistent with this picture is the much smaller shift, in either direction, of the a-carbon atoms. Studies were extended to include ap-unsaturated acids and esters. ... 

A (trimethylsilyl)cyclopentene annulation method has been developed that leads to a regiocontrolled approach to the synthesis of five-membered rings/ Thus, it was shown that (trimethylsilyl)allenes could be persuaded to react at -78 C with unsaturated carbonyl compounds in the presence of titanium tetrachloride (Scheme 16). The methodology is presently being applied to polyquin-ane natural product synthesis. 

Reactions of similar organoalkynyl/allenyl silanes containing various metals with carbonyl compounds to give propargylic products have been reported. " Conjugate addition of allenyl stan-nanes to Q , -unsaturated carbonyl compounds to give propargylic products can be effected in the presence of titanium(IV) chloride. ... 

Synthesis of Five-Membered Carbocycles. 1-Substituted al-lenylsilanes react with Q ,/3-unsaturated carbonyl compounds in the presence of titanium tetrachloride to produce cyclopentenes. For example, carvone and 1-methyl-l-(trimethylsilyl)allene react smoothly to give a ds-fused bicyclic system (eq 7). ... 

Similar to the results discussed for the silylcarbocyclizations of carbon-carbon multiple bonds, reductive cyclizations in the presence of carbonyl compounds are readily achieved. Crowe has developed a titanium-catalyzed procedure for the intramolecular reductive coupling of i5, -unsaturated carbonyl compounds in the presence of triethoxysilane (eq 18).The electronic advantage of triethoxysilane is demonstrated by the lack of reductive coupling in the presence of less reactive silanes, such as triethylsilane and diphenylsilane. With this method, Mori has utilized nickel(O) catalysts to generate five- and six-membered carbocycles and pyrrolidine derivatives. Furthermore, coordination of a chiral phosphine ligand to the nickel catalyst renders the reaction moderately enantioselective. ... 

Titanium(ii)-chloride-induced reductive cyclization of one of the photo-adducts (43) of isoprene and methyl 2,4-dioxopentanoate produced a mixture of diastereo-meric diols (44), which are useful precursors in the synthesis of iridoids. The Lewis-acid-catalysed reaction of unsaturated carbonyl compounds such as (45) shows a strong dependence on the strength and quantity of Lewis acid used. 

A full report of the Michael reaction of silyl enol ethers with a/S-unsaturated ketones is noted a convenient method for the preparation of S-keto-esters entails titanium(iv)-promoted Michael-type additions of o-silylated keten acetals with ajS-unsaturated carbonyl compounds. ... 

Similarly to alkenes, alkynes react with various titanium-methylidene precursors, such as the Tebbe reagent [13,63], titanacydobutanes [9b, 64], and dimethyltitanocene [65] to form the titanium-containing unsaturated cyclic compounds, titanacydobutenes 67 (Scheme 14.29). Alternatively, 2,3-diphenyltitanacydobutene can be prepared by the reaction of the complex titanocene(II) bis(trimethylphosphine) with 1,2-diphenylcyclopropene [66]. Substituent effects in titanacydobutenes [67], the preparation of titanocene-vinylke-tene complexes by carbonylation of titanacydobutenes [68], and titanacyclobutene-vinylcar-bene complex interconversion [69] have been investigated. 

Synthetically even more versatile trifunctional intermediates result from the addition of carbonyl compounds onto methyl 2-siloxycyclopropanecarboxylates 92). Benzo-phenone, titanium tetrachloride, and 162, for instance, provide an excellent yield of the a-hydroxyalkylated y-oxoester 174, which predominates in the equilibrium with its cyclic hemiacetal 176 (y-lactol). It can undergo elimination to the unsaturated ester 175, but as Scheme 7 illustrates, 174/176 can also serve as the starting material to several highly substituted furan(one) derivatives. 

In addition to enol silyl ethers, an optically active boryl enolate underwent the highly anri-stereoselective aldol reaction with a wide variety of aldehydes in the presence of TiCU (Eq. 34) [120]. The vinyl sulfides shown in Eq. (35) reacted with a,fi-unsaturated ketones via the 1,4-addition pathway in the presence of a titanium salt, but the reaction was followed by the cleavage of a carbon-carbon bond in the cycloalkane to give open chain products in a stereoselective manner [121]. The 1,2-type addition was observed, if the olefinie acetal was used instead of the corresponding carbonyl compound, as shown in Eq. (36) [121], The successive scission of the carbon-carbon bond took place analogously to give the same type of products as shown in Eq. (35). 

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