Ketones titanium reagents

Alkene R1 Ketone Titanium Reagent Temp. (°C) d.r. (anti/syn) Yield (%) Ref... 

Stereoselectivities of 99% are also obtained by Mukaiyama type aldol reactions (cf. p. 58) of the titanium enolate of Masamune s chired a-silyloxy ketone with aldehydes. An excess of titanium reagent (s 2 mol) must be used to prevent interference by the lithium salt formed, when the titanium enolate is generated via the lithium enolate (C. Siegel, 1989). The mechanism and the stereochemistry are the same as with the boron enolate. 

Very high levels of induced diastereoselectivity are also achieved in the reaction of aldehydes with the titanium enolate of (5)-l-rerr-butyldimethylsiloxy-1-cyclohexyl-2-butanone47. This chiral ketone reagent is deprotonated with lithium diisopropylamide, transmetalated by the addition of triisopropyloxytitunium chloride, and finally added to an aldehyde. High diastereoselectivities are obtained when excess of the titanium reagent (> 2 mol equiv) is used which prevents interference by the lithium salt formed in the transmetalation procedure. Under carefully optimized conditions, diastereomeric ratios of the adducts range from 70 1 to >100 1. 

The titanium reagent also dimethylates aromatic aldehydes." Triethylaluminum reacts with aldehydes, however, to give the mono-ethyl alcohol, and in the presence of a chiral additive the reaction proceeds with good asymmetric induction." A complex of Me3Ti-MeLi has been shown to be selective for 1,2 addition with conjugated ketones, in the presence of nonconjugated ketones." ... 

Because in the case of a sterically crowded imidazolide the formation of a carbinol is more difficult, reaction with the titanium reagent or the corresponding Grignard compound produces the allyl ketone in about the same yield [96]... 

Alkylidenecydopropane derivatives can readily be prepared by the reaction of 1 with vinylcyclopropyl carbonates and subsequent trapping of the resulting allyltitaniums with aldehydes or ketones (Eq. 9.24) [44], It should be noted that, in this case, the carbon—carbon bond formation occurs at the less substituted allylic terminus, and not at the more substituted end of the titanium reagent, the latter being the position at which addition to substituted allyltitanium reagents is usually observed. 

Aldol-type reaction of zinc esters. This titanium reagent promotes condensation of (ethoxycarbonylalkyl)iodozinc compounds (13, 220) with aldehydes or ketones to provide hydroxy esters and/or lactones. The active reagent may be (ethoxycarbonyl)alkyltriisopropoxytitanium. 

An alternative, but related, route to allenic titanium reagents from propargylic esters has been reported recently. Reaction of titanocene dichloride with BuMgCl and Mg yields a reactive titanocene intermediate, formulated as Cp2Ti. This reduced Ti species reacts in situ by oxidative addition to propargylic acetates. The allenyltitanium reagents thus produced add to aldehydes and ketones, as expected, to afford homopropargylic alcohols (Table 9.27) [43]. 

An interesting deoxygenation of ketones takes place on treatment with low valence state titanium. Reagents prepared by treatment of titanium trichloride in tetrahydrofuran with lithium aluminum hydride [205], with potassium [206], with magnesium [207], or in dimethoxyethane with lithium [206] or zinc-copper couple [206,209] convert ketones to alkenes formed by coupling of the ketone carbon skeleton at the carbonyl carbon. Diisopropyl ketone thus gave tetraisopropylethylene (yield 37%) [206], and cyclic and aromatic ketones afforded much better yields of symmetrical or mixed coupled products [206,207,209]. The formation of the alkene may be preceded by pinacol coupling. In some cases a pinacol was actually isolated and reduced by low valence state titanium to the alkene [206] (p. 118). 

By the use of chiral oxazolidines derived from a chiral norephedrine and methyl ketones, an asymmetric aldol reaction proceeds in a highly enantioselective manner. In the case of ethyl or a-methoxy ketones, the corresponding anti aldol products were obtained with high diastereo- and enantioselectivities. A chiral titanium reagent, generated from... 

Oxo esters undergo an intramolecular dicarbonyl coupling reaction on treatment with a low-valent titanium reagent to form a ketone. This was used in the synthesis of (Z)-7,l0,10-trimethyl-bicyclo[7.2.0]undec-6-en-2-one (4) from ethyl ( )-6-methyl-7-(4,4-dimethyl-2-oxocyclobutyl)-hept-5-enoate,108 Interestingly, the configuration of the isolated C -C double bond in the isolated product is sensitive to the reaction conditions. 

Preparation Essentially this reaction involves the preparation of a low-valent titanium reagent that then couples carbonyl groups, including esters to aldehydes/ketones. Generally, TiCLt is reduced with some reducing agent (LiAIH4, Zn, Mg). 

Diastereospecific aldol condensations,u The titanium enolate of the chiral ketone 1 reacts with aldehydes to give mainly the syn-aldol (—90 10). However, use of excess titanium reagent or addition of 12-crown-4 (which complexes Li+) results in >99 1 diastereoselectivity. 

Apart from the Takai method and titanium reagents such as 15, silyl reagents 16 and 17 frequently find application in the synthesis of vinylic silanes from carbonyl compounds. Reagent 16 can be utilized with aldehydes and non-enolizable ketones in a reaction analogous to the Peterson olefination Reagent 17 also reacts successfully with enolizable ketones.6... 

More recently Ito and Mikami observed" that the titanium reagent is not indispensable in the case of highly basic lithium enolates derived from cyclic ketones or silyl enolates, for which the reactions are very fast (ending in ca Is to 5 min) and afford high yields of the a-trifluoromethylation products. A tentative radical mechanism has been proposed for these processes" involving reaction of the Mef free radical with the enolate to give a radical intermediate which reacts with another MefI molecule to afford Mef and the a-trifluoromethylation product (equation 42). 

Reductive cyclization of 2-(t>/X t>-nitro)phenyl imidazoles 817, 819 (Scheme 203) in the presence of an orthoester or a ketone is promoted by a low-valent titanium reagent TiCU-Zn to afford imidazo[l,2-f]quinazolines 818 and 5,6-dihydroimidazo[l,2-r ]quinazolines 820 <2005JHC173>. Notably, halogens are not reduced under these conditions. 

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