Titanium, methyl reactions with carbonyl compounds

Alkenyl sulfides are known to react with some labile electron-deficient olefins such as methyl vinyl ketone in the presence of AlCl3 to form cyclobutanes [25]. In the present chiral titanium-promoted asymmetric reaction, alkenyl sulfides can also be employed as electron-rich components. 2-Ethylthio-l-propene (7a) reacts with 2a in the presence of a catalytic amount of the chiral titanium reagent, giving the diastereomeric [2-1-2] cycloaddition products 8a and 9a in 51% (>98% ee) and 19% (79% ee) yields, respectively (Scheme 7 and Table 2). Although 2-ethylthio-l-propene (7a) is known as a good ene component in the reaction with carbonyl compounds, 3-(3-(methoxycarbonyl)-5-ethylthio-5-hex-enoyl)-l,3-oxazolidin-2-one, an ene product, is obtained only in 16% yield as a side product. 

The interest in chiral titanium(IV) complexes as catalysts for reactions of carbonyl compounds has, e.g., been the application of BINOL-titanium(IV) complexes for ene reactions [8, 19]. In the field of catalytic enantioselective cycloaddition reactions, methyl glyoxylate 4b reacts with isoprene 5b catalyzed by BINOL-TiX2 20 to give the cycloaddition product 6c and the ene product 7b in 1 4 ratio enantio-selectivity is excellent - 97% ee for the cycloaddition product (Scheme 4.19) [28]. 

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... 

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. ... 

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... 

The direct selenoacetalization of carbonyl compounds by selenols is by far the shortest and most convenient route to selenoacetals. The reaction is usually carried out at 20 C with zinc chloride (0.5 equiv. versus the carbonyl con x>und) and delivers rapidly (<3 h) and in reasonably good yields methyl and phenyl selenoacetals derived from aliphatic aldehydes and ketones and cyclic ketones (Scheme 69). Selenoacetalization is more difficult to achieve with hindered ketones, such as adamantanone and diisopropyl ketone, and with hindered aromatic carbtmyl compounds. In these cases the reaction is best achieved with titanium tetrachloride instead of zinc chloride and is often limited to the methylseleno derivatives (Scheme 78). Tris(methylseleno)borane offers the advantage of not requiring an acid catalyst and is particularly useful for the selenoacetalization of acid labQe aldehydes such as citronellal (Scheme 70, e). 

A standard method for enamines synthesis from carbonyl compounds is to heat the parent aldehyde or ketone and a secondary amine in benzene or toluene and to remove the eliminated water by azeotropic distillation. However, this method fails with methyl ketone substrates which are prone to self-condensation imder these conditions. These difficulties could be overcome by a procedure using anhydrous titanium tetrachloride as water scavenger.[6] In the original procedure, titanium tetrachloride was added dropwise to a cold solution of the ketone and the amine, followed by prolonged stirring at room temperature. It was later found that the reaction time could be considerably shortened by a modified procedure, in which the... 

The mechanism of carbonyl methylenation with dimethyltitanocene 30 is one of the major subjects of discussion in titanium-carbene chemistry. Two reaction pathways have been proposed. Based on the observation of H/D scrambling in reactions using a deuterated ester and Cp2Ti(CD3)2, Petasis proposed that the reaction proceeds by methyl transfer to form the adduct 31 and subsequent elimination of methane and titanocene oxide (Scheme 4.29, Path A) [64]. Later, a detailed study by Hughes and co-workers using and D-labeled compounds showed that the methylenation of esters with 30 proceeds via a titanium carbene mechanism (Path B) [82]. 

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