Titanium, tris enolates

Titanium enolates, which are weak Lewis acids, add to 2-alkoxyaldehydes with remarkable stereoselectivity under nonchelation control 1. Thus, 2-benzyloxypropanal is attacked by the tris(isopropyloxy)titanium enolate 7 preferably from the 57-face, to give a 87 13 mixture of adducts with complete simple diastereoselectivity3,1. 

In contrast to titanium enolates of ketones, titanium enolates of aldehydes exhibit practically no stereoselectivity in aldol reactions. However, titanation of dimethylhy-drazones of aldehydes with 1 results in substrates (2) that show high eryt/iro-selecti v i ty in aldol-type reactions with aldehydes (equation I). Bromotitanium tris(diethylamide) can be used in place of 1, but is less efficient, as is Ti(IV) isopropoxide.6... 

Allyl silanes react with a wide variety of electrophiles, rather like the ones that react with silyl enol ethers, provided they are activated, usually by a Lewis acid. Titanium tetrachloride is widely used but other successful Lewis acids include boron trifluoride, aluminium chloride, and trim ethyls ilyl tri-flate. Electrophiles include the humble proton generated from acetic add. The regiocontrol is complete. No reaction is observed at the other end of the allylic system. All our examples are on the allyl silane we prepared earlier in the chapter. 

We have prepared a number of titanium enolates by quenching the lithium analogs withchlorotitanium triisopropoxide 3, chloro- or bromotitanium tris(diethylamide) 15 or chlorotitanium tris(dimethylamide) 103 25). In mqst cases the solutions can be freed from the ether or THF and the stable liquid titanium enolates studied by NMR if so desired. In case of the amino derivative 186 flash distillation is possible. The H-NMR spectra of the distilled and non-distilled compound are identical and... 

As shown in Scheme 38, several primary alkyl-substituted cyclohexanones have been prepared by Lewis acid catalyzed phenylthioalkylation of the TMS enol ether of cyclohexanone followed by reductive removal of a phenylsulfenyl group. The two-step neopentylation sequence is particularly noteworthy. This methodology has been used to prepare numerous a-alkylated cyclic and acyclic ketones. a-Alkylated aldehydes can be produced in a like manner. a-Alkylidenation can also be accomplished by oxidative removal of sulfur. Lee and coworkers have found that TMS triflate-catalyzed reactions of silyl enol ethers of cyclic ketones and aldehydes with saturated and unsaturated l,l-dimethoxy-(i>-tri-methylstannanes, followed by addition of titanium tetrachloride, provide novel routes to fused and spiro-cyclic ring systems. Phenylthiomethylstannylations of silyl enol ethers have also been reported. ... 

Formaldehyde is a versatile reagent as one of the most highly reactive Q electrophiles in organic synthesis [9, 10] and dry gaseous formaldehyde has been required for many reactions. For example, the titanium tetrachloride (TiCl4)-promoted hydroxymethylation reaction of a silyl enol ether was carried out by using tri-oxane as an HCHO source under strictly anhydrous conditions [11, 12]. Formalde-hyde/water solution could not be used because TiCl4 and the silyl enol ether reacted with water rather than with HCHO in that aqueous solution. 

Titanium enolates of cyclic and acyclic ketones, like their zirconium counterparts, usually give rise to syn aldol products irrespective of enolate geometry. Tri(alkoxy)- or tri(dialkylamino)-titanium enolates... 

Table 3 SynAnti Selectivity in the Aldol Reactions of Tri(isopropoxy)- and Tri(diethylamino)-titanium Enolates...

These tri(alkoxy)titanium enolates, which have low Lewis acidity, are known to react chemoselective-ly with an aldehyde group in the presence of a ketone (equation 4). Other uses described by Reetz et al. include the diastereofacially selective additions of ketone and ester enolates to chiral a-alkoxy aldehydes with nonchelation control. - For example, aldol addition of the tri(isopropoxy)titanium enolate of pro-piophenone to the aldehyde (24) leads to only the two syn diastereomers, with the nonchelation adduct (25) favored (equation 5) i.e. Felkin-Anh selectivity is operating. In the case of aldol addition of t-butyl propionate to the same aldehyde (equation 6), highest stereoselectivity for the isomer (26) is obtained using the tri(diethylamino)titanium enolate. Very high levels of nonchelation stereoselectivity can also be obtained in the aldol addition to chiral a-siloxy or a-benzyloxy ketones if a titanium enolate of low Lewis acidity is employed, as in equation (7). ... 

In some cases titanium enolates give as good, if not better, stereoselectivity as the corresponding boron enolate aldol reactions (Volume 2, Chapter 1.7). For example, the tri(isopropoxy)titanium enolate of the chiral ethyl ketone (27) has been found to undergo aldol reactions with aldehydes with very high dia-... 

Titanium enolates can be prepared from lithium enolates by reaction with a trialkoxytitanium(IV) chloride, such as tri-(isopropoxy)titanium chloride. Titanium enolates can also be prepared directly from ketones by reaction with TiCl4 and a tertiary amine." ... 

We urge you to try to write a mechanism for the above process. You may find it useful to think of silyl groups as fat protons. Start off with silylating the carbonyl oxygen and proceed from there. Silyl enol ethers function as less reactive analogs of enolate anions. Thus, with titanium tetrachloride as a catalyst, silyl enol ethers undergo aldol condensations with a variety of carbonyl compounds. This is the Mukaiyama aldol condensation ... 

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