Titanium enolates structure

Seebach and Brenner have found that titanium enolates of acyl-oxazolidinones are added to aliphatic and aromatic nitroalkenes in high diastereoselectivity and in good yield. The effect of bases on diastereoselectivity is shown in Eq. 4.59. Hydrogenation of the nitro products yields y-lactams, which can be transformed into y-amino acids. The configuration of the products is assigned by comparison with literature data or X-ray crystal-structure analysis. 

An exceptionally mild procedure for the cross-condensation of aldimines and enolsilanes has been described (eq. [67]) (80). This titanium tetrachloride-mediated reaction is predicated on the previous analogies provided by Mukaiyama for related aldol condensations (73a). Depending on aldimine structure and reaction time, either -lactams or their penultimate amino esters may be isolated from the reaction. The authors postulate that these reactions are proceeding via titanium enolates derived from ligand exchange by... 

The aldol reactions of the titanium Z-enolates proceeded smoothly with various aldehydes precomplexed with titanium chloride at -78° C. The diastereose-lectivity is high to excellent, with the single exception of benzaldehyde. The high degree of diastereoselection associated with this current asymmetric anti-aldol process can be rationalized by a Zimmerman-Traxler type of six-membered chairlike transition state Al9fl (Scheme 2.2r). The model is based on the assumptions that the titanium enolate is a seven-membered metallocycle with a chairlike conformation, and a second titanium metal is involved in the transition state, where it is chelated to indanolyloxy oxygen as well as to the aldehyde carbonyl in a six-membered chairlike transition-state structure. 

Consecutive nuclear Overhauser enhancement spectroscopy (NOESY) experiments allowed one to calculate the distance between the enolate proton and other protons in the octahedrally coordinated titanium enolate 13. The H -tf and H -H- distances calculated from NMR spectra are 0.2 A longer or 0.5 A shorter, respectively, than those in the model structures. Using modeling studies, the same prediction can be observed, indicating that one side of the Ti enolate complex is less sterically hindered than the other side. This is due to the efficient diffusion pathway formed by the enolate H (H ), the protons on the i-Pr group (H, Me) and the protons on the selone heterocycle (H, H ). These distances confirm that the enolate oxygen atoms are cis to each other and their orientation should promote a strong facial preference upon subsequent reaction with an aldehyde or ketone. 

A highly versatile auxiliary is the Evans oxazolidinone imide (Figure 5.4c, see also Scheme 3.16), available by condensation of amino alcohols [86,87] with diethyl carbonate [86]. Deprotonation by either LDA or dibutylboron triflate and a tertiary amine affords only the Z(0)-enolate. Scheme 5.12 illustrates open and closed transition structures that have been postulated for these Zf0)-enoIates under various conditions, and Table 5.4 lists typical selectivities for the various protocols. The first to be reported (and by far the most selective) was the dibutylboron enolate (Table 5.4, entry 1), which cannot activate the aldehyde and simultaneously chelate the oxazolidinone oxygen [75]. Dipolar alignment of the auxiliary and approach of the aldehyde from the Re face of the enolate affords syn adduct with outstanding diastereoselection, presumably via the closed transition structure illustrated in Scheme 5.12a [75]. The other syn isomer can be formed under two different types of conditions. In one, a titanium enolate is postulated to chelate the oxazolidinone... 

These four examples do not seem to comply with a consistent mechanistic model. The dilithioprolinol amide enolate in Scheme 5.31a is attacked on the enolate Si face, in accord with the sense of asymmetric induction observed in alkylations of this enolate [166,167]. On the other hand, the structurally similar dilithiovalinol amide enolate, while being attacked on the same face (as expected), reverses top-icity. Furthermore, the S,S-pyrrolidine enolate in Scheme 5.31c is attacked from the Si face by Michael acceptors, but from the Re face by alkyl halides [168] and acid chlorides [169]. The titanium imide enolate in Scheme 5.31d adds Michael acceptors from the Si face, consistent with the precedent of aldol additions of titanium enolates (c/. Table 5.4, entry 2, [88]). An intramolecular addition (Scheme 5.3le) seems to follow a clear mechanistic path [165] the Si face is attacked by the electrophile, and the cis geometry of the product implicates intramolecular complexation of the acceptor carbonyl. This coordination of the acceptor carbonyl is probably a function of the metal recall the lithium ester enolates illustrated in Scheme 5.30c and d, but also metal chelation in titanium aldol additions (Table 5.4, entry 2). 

Asymmetric aldol reactions. The chiral N-propionyloxazolidinone (1), prepared in several steps from (lR)-(—)-camphorquinone, undergoes highly diastereoselective aldol reactions with the additional advantage of high crystallinity for improving the optical purities of crude aldols. Either the lithium enolate or the titanium enolate, prepared by transmetalation with ClTi(0-(-Pr)3, reacts with aldehydes to form syn-adducts with diastereomeric purities of 98-99% after one crystallization. The observed facial selectivity is consistent with metal chelation of intermediate (Z)-enolates (supported by an X-ray crystal structure of the trapped silyl enol ether). The lithium enolate also exhibits... 

After almost half century of intensive, fundamental, and fruitful investigations of enolate structures, there is now clear evidence indicating that enolates of groups 1, 2, and 13 metals - lithium and boron being the most relevant ones - exist as the O-bound tautomers 1 the same holds in general for silicon, tin, titanium, and zirconium enolates [4]. Numerous crystal structure analyses and spectroscopic data confirmed type metalla tautomer 1 to be the rule for enolates of the alkali metals, magnesium, boron, and silicon [5]. 

Titanium enolates are generally prepared by transmetalation of alkali-metal enolates but may also arise as structural parts of intermediates in TiCU-promoted reactions. This is illustrated in a stereoselective alkylation using an oxazolidinone as a chiral auxiliary (eq 11). The enolate, or its ate complex, may be the intermediate in the reaction. ... 

The pharmaceutical interest in the tricyclic structure of dibenz[6,/]oxepins with various side chains in position 10(11) stimulated a search for a convenient method for the introduction of functional groups into this position. It has been shown that nucleophilic attack at the carbonyl group in the 10-position of the dibenzoxepin structure renders the system susceptible to water elimination. Formally, the hydroxy group in the enol form is replaced by nucleophiles such as amines or thiols. The Lewis acids boron trifluoride-diethyl ether complex and titanium(IV) chloride have been used as catalysts. 

Summary of Facial Stereoselectivity in Aldol and Mukaiyama Reactions. The examples provided in this section show that there are several approaches to controlling the facial selectivity of aldol additions and related reactions. The E- or Z-configuration of the enolate and the open, cyclic, or chelated nature of the TS are the departure points for prediction and analysis of stereoselectivity. The Lewis acid catalyst and the donor strength of potentially chelating ligands affect the structure of the TS. Whereas dialkyl boron enolates and BF3 complexes are tetracoordinate, titanium and tin can be... 

Ketones and nitriles are rather soft bases their coordination onto electron-deficient sites on oxides is, therefore, relatively weak. One may, however, expect an improved specificity of chemisorption due to their softness. Unfortunately, however, these substances very easily undergo chemical transformations at oxide surfaces. Thus, carboxylate structures are formed on adsorption of acetone on alumina (194, 245-247), titanium dioxide (194), and magnesium oxide (219, 248, 249). Besides, acetone is also coordinated onto Lewis acid sites. A surface enolate species has been suggested as an intermediate of the carboxylate formation (248, 249). However, hexafluoroacetone also leads to the formation of trifluoroacetate ions (219). The attack of a basic surface OH ion may, therefore, be envisaged as an alternative or competing reaction path ... 

P-Diketone Chelates. P-Diietones, reacting as enols, readily form chelates with titanium atkoxides, liberating in the process one mole of an alcohol. TYZOR AA [17927-72-9] (6) is the product mixture from TYZOR TPT and two moles of acetylacetone (acac) reacting in the enol form. The isopropyl alcohol is left in the product (87). The dotted bonds of structure (6) indicate electron... 

Based on the optimization of the structures of titanium and lithium enolates, it has been shown that, although Ti—F bonds are stronger than Li—F bonds, the stability of... 

Keck also investigated asymmetric catalysis with a BINOL-derived titanium complex [102,103] for the Mukaiyama aldol reaction. The reaction of a-benzyloxyalde-hyde with Danishefsky s dienes as functionalized silyl enol ethers gave aldol products instead of hetero Diels-Alder cycloadducts (Sch. 40) [103], The aldol product can be transformed into hetero Diels-Alder type adducts by acid-catalyzed cyclization. The catalyst was prepared from BINOL and Ti(OPr )4, in 1 1 or 2 1 stoichiometry, and oven-dried MS 4A, in ether under reflux. They reported the catalyst to be of BINOL-Ti(OPr% structure. 

The H NMR spectra (471, 472) of yttrium, lutetium, and titanium derivatives are consistent with structures in which the oxygen atom of the enolate bonds to the metal center. Resonances due to the =CH group appear as doublets of doublets. The signals due to the =CH2 protons appears as two doublets... 

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