Transition state/structure chelated

Proper selection of the reaction solvent is important to attain high yields and selectivities, especially in reactions using a-substituted terminal allylic alcohols. Less coordinating solvents such as dichloromethane or toluene should be employed. With THF as the solvent, magnesium ion coordination slows the rate and lowers the diastereoselectivities (Scheme 11.30), which indicates that chelation plays an important role in the transition state structure of the magnesium ion-mediated reaction. 

Mikami has also reported a related ene-like process involving glyoxylates and ketone-derived enolsilanes 42 (Eq. 8B2.11) [17]. The enol ether adducts 43 yield the corresponding P-hydroxy ketone upon treatment with mild acid. On the basis of an analysis of the stereo- and regiochemical outcome of the addition reaction Mikami has invoked a monodentate complex between aldehyde and metal, in contrast to the typical transition-state structures involving glyoxylates that are suggested to involve metal/aldehyde chelates. 

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. 

A high degree of stereoselectivity can be realized under chelation control, where an oxygen atom of an ether function (or more generally a Lewis base) in the a-, P- or possibly y-position of carbonyl compounds can serve as an anchor for the metal center of a Lewis acid. Since Cram s pioneering work on chelation control in Grignard-type addition to chiral alkoxy carbonyl substrates [30], a number of studies on related subjects have appeared [31], and related transition state structures have been calculated [32], Chelation control involves Cram s cyclic model and requires a Lewis acid bearing two coordination sites (usually transition metal-centered Lewis acids). 

When TiCU is used as a catalyst with substituted dienes such as (14), a predominant route is the Mu-kaiyama aldol process, " When diene (14) reacts with benzaldehyde the trans (anti) product is observed. When compound (42) is used as the aldehyde, one observes exclusive formation of the (erythro) aldol products (Table 14). These stereochemical results can be rationalized by using a Zimmerman-Traxler transition state (Scheme 18). Chelation by the metal of the aldehyde a-alkoxy group causes it to be placed in a pseudo axial position in the transition state structure. This results in a stereochemical relationship that gives syn aldol products. ... 

The next level in the development of these methods was achieved by introducing chelating chiral imines that, as a result of a more rigid transition state structure, enabled better chiral induction. The best results were obtained with a methyl ether chelating arm 92. Application of such... 

There are numerous noteworthy structural aspects of N-acyl oxazolidinones that give them a central role as auxiliaries for a large array of asymmetric transformations. Although the enolization reaction of esters and ketones can lead to mixtures of cis- and trans-enolates, the oxazolidinone imi-des exclusively form the corresponding cis-enolates. This observation has been attributed to the pronounced destabilization of the trans-enolate and the transition state structure leading to its formation as a consequence of A, 3 steric interactions (cf 124, Scheme 3.19) [15]. A second important feature of the oxazolidinone enolates relates to the ability of the auxiliary carbonyl functionality to form a chelate with coordinatively unsaturated metal centers (cf 118,121, or 125). This organizing feature provides rigidity to the en-... 

Gosh independently reported another anti-selective aldol addition process employing aminoindanol-derived esters 114 (Equation 11) [72]. These were subjected to enolization with excess TiCl, and Hiinig s base to furnish titanium 2-enolates, as determined by NMR spectroscopy. Addition reactions with a variety of aliphatic and unsaturated aldehydes, precomplexed with TiCl4, furnished the anti aldol adducts such as 116 in 44—97% yields and up to 99 1 anti/syn ratios of diastereomers. The stereochemical outcomes of the reactions have been attributed to chelated Zimmerman-Traxler transition state structures, such as 115. It is interesting to note that benzaldehyde, as the only aromatic aldehyde examined, yielded a 1 1.1 mixture of antijsyn products. 

Use of y-alkoxy-substituted allylic stannane reagents with a-benzyloxy aldehydes provides convenient access to 1,2,3-triol subunits (Equation 8) [92]. Keck reported the chelation-controlled formation of 113 as a single dia-stereomer and suggested that this product is the result of the intermediacy of transition state structure 112, analogous to 100. 

I-Oialkoxy carbonyl compounds are a special class of chiral alkoxy carbonyl compounds because they combine the structural features, and, therefore, also the stereochemical behavior, of 7-alkoxy and /i-alkoxy carbonyl compounds. Prediction of the stereochemical outcome of nucleophilic additions to these substrates is very difficult and often impossible. As exemplified with isopropylidene glyceraldehyde (Table 15), one of the most widely investigated a,/J-di-alkoxy carbonyl compoundsI0S, the predominant formation of the syn-diastereomer 2 may be attributed to the formation of the a-chelate 1 A. The opposite stereochemistry can be rationalized by assuming the Felkin-Anh-type transition state IB. Formation of the /(-chelate 1C, which stabilizes the Felkin-Anh transition state, also leads to the predominant formation of the atm -diastereomeric reaction product. 

The high diastereoselectivity which is found in the nucleophilic addition of Grignard reagents to chiral 2-0x0 acetals can be explained by a chelation-controlled mechanism. Thus, coordination of the magnesium metal with the carbonyl oxygen and the acetal moiety leads to a rigid structure 3A in the transition state with preferred attack of the nucleophile occurring from the S/-side. 

The diastereoselectivity of the reaction may be rationalized by assuming a chelation model, which has been developed in the addition of Grignard reagents to enantiomerically pure a-keto acetals7,8. Cerium metal is fixed by chelation between the N-atom, the methoxy O-atom and one of the acetal O-atoms leading to a rigid structure in the transition state of the reaction (see below). Hence, nucleophilic attack from the Si-face of the C-N double bond is favored4. 

The high level of enantiofacial selection is made in the hydride transfer step 7C -> 7D [2], The chelating geometry in the transition state 7F decreases the activation energy. The chiral environment derived from (R)-BINAP clearly differentiates diastereomeric Si-7F and Re-7F (Fig. 32.7b). The Si structure affording the R alcohol is much more favored than the Re structure, which suffers from the Ph/R repulsion. 

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