Magnesium enolates chiral

Aldol reactions of simple amide enolates give poor stereoselection. Stimulated by the interest in /3-lactams, the stereochemistry of aldol reactions of chiral magnesium enolates of /3-lactams has been studied . The best results have been obtained with 6,6-dibromopenams 85 (equation 108). After bromine-magnesium exchange with MeMgBr,... 

Other chiral magnesium enolates derived from amides are known to react with aldehydes. For example, the aldol-type reaction of magnesium enolate of —)-trans-2-N,N-diethylacetamide-l,3-dithiolanes-5 -oxide with isobutyraldehyde affords a single diastere-omer in 82%. The relative stereochemistry of the adduct originates from a rigid transition state 87 where the oxygen atoms of the enolate and the aldehyde are coordinated to the magnesium atom. ... 

Copper Conjugate addition of Grignard reagents to cyclic enones (249), catalysed by the Cu complex of Taniaphos (248), followed by Mannich reaction of the resulting chiral magnesium enolates with Af-protected imines, has been shown to produce the adducts (250) with <98% ee. Diastereoselectivity turned out to be dependent on the... 

Mechanistic studies indicate that the reaction proceeds via initial coordination of the 1,3-dicarbonyl compound to the magnesium center, acidifying the 2-proton. Deprotonation by the amine base results in a chiral magnesium enolate which ad diastereoselectively to the nitroalkene to set the new chiral center. 

The introduction of asymmetry in conjugate additions can be promoted by chiral acceptors. The preparation of regio-defined magnesium enolates from copper(I)-mediated conjugate addition of Grignard reagents has been extensively used in many important... 

Three chiral intermediates are observed directly by H and NMR spectroscopy one olefin-copper(I) complex 26 and two magnesium enolates 27 and 28 (equation 43). 

Nnmerons other protocols have been developed to prepare magnesium enolates by asymmetric 1,4-addition of Grignard reagents to electron-deficient alkenes. Recently, an enantioselective metal-catalyzed version of this key reaction has been studied with enones and a, S-unsaturated thioesters Using chiral ferrocenyl-based diphosphines leads to... 

The concept of chiral magnesium amides for the preparation of magnesium enolates has been extended to chiral magnesium bis(sulfonamide) complexes as catalysts for the enolization of A-acyloxazolidines ° (equation 63). 

In addition to the structural effects due to the geometry of a substituted magnesium enolate, the stereochemistry of the reaction with a chiral aldehyde can be controlled, as described in equation 85. The aldol reaction based on the addition of magnesium enolate 56 to aldehyde 55 has been applied to the synthesis of monensin. The chiral center in the aldehyde induces the preferential approach of one diastereotopic face of the aldehyde by... 

The enantioselective amination of iV-acyl oxazolidinones has been studied as part of a general approach to the synthesis of arylglycines. In this case, the enolization is initiated by a chiral magnesium bis(sulfonamide) complex. The oxazolidinone imide enolates are generated using catalytic conditions (10 mol% of magnesium complex) and treated in situ with BocN=NBoc to provide the corresponding hydrazide. 20 mol% of iV-methyl-p-toluensulfonamide are added to accelerate the reaction (equation 117). 

An interesting class of chiral enolates are allenyl enolates. These ambident nucleophiles bear an axis of chirality. Krause and coworkers have found that an axis to center chirality transfer takes place in the aldol reaction of chiral magnesium allenyl enolate with pivalic aldehyde . The aldol reaction proceeds with good diastereofacial selectivity if... 

The chemistry of magnesium bisamides has been reviewed" . They can be used for the regio- and stereoselective formation of enolates", while chiral magnesium amides are applied in asymmetric synthesis for enantioselective enolisations ". 

The chemistry of magnesium bis-amides has been reviewed.21 Magnesium bis-amides have been used for the region- and stereoselective formation of enolates.2 a Enantioselective enolization with chiral magnesium amides has been applied in asymmetric synthesis.23 233... 

Interesting investigations were carried ont by Brann and coworkers in diastereoselec-tive and enantioselective palladinm-catalyzed allyUc snbstitutions with the nonstabUized magnesium enolate of cyclohexanone (51, eqnation 16) . With (/f)-BINAP as chiral ligand the syn product 53 was obtained nearly exclnsively with high enantiomeric excess and quantitative conversion of the starting material 52. 

Aldol-Type Addition. Aldol-type addition of the magnesium enolate of (R)-(+)-7-butyl 2-(p-tolylsulfinyl)acetate, prepared with 7-butylmagnesium bromide, with aldehydes and ketones afforded, after desulfurization with Aluminum Amalgam, p-hydroxy esters in very high diastereoselectivity (eq Two chiral centers are created in the first step with very high diastereoselectivity (mainly one diastereomer is formed). A model M based on the structure of the sulfinyl ester enolate (determined by C NMR) and on electrophilic assistance of magnesium to the carbonyl approach, was proposed to explain and predict the absolute configuration of the two created chiral centers. ... 

Silyl enol ethers react with aldehydes in the presence of chiral boranes or other additives " to give aldols with good asymmetric induction (see the Mukaiyama aldol reaction in 16-35). Chiral boron enolates have been used. Since both new stereogenic centers are formed enantioselectively, this kind of process is called double asymmetric synthesis Where both the enolate derivative and substrate were achiral, carrying out the reaction in the presence of an optically active boron compound ° or a diamine coordinated with a tin compound ° gives the aldol product with excellent enantioselectivity for one stereoisomer. Formation of the magnesium enolate anion of a chiral amide, adds to aldehydes to give the alcohol enantioselectively. 

Aldol reactions of chiral dioxolanones (113) and (114) are summarized in Scheme 6 and Table 9. ° With both (113) and (114), essentially perfect diasterofacial selectivity is observed. The simple dia-stereoselection is modest to good, and is dependent on the enolate counterion. For the lithium and magnesium enolates, the sense of simple diastereoselection is the same as is observed with the achiral dioxolanone (107) and the chiral dioxolanone (110). Use of the zirconium enolate generally reverses the sense of simple diastereoselection, although the isomer ratios are not very high in some cases. 

In this section are treated aldol reactions of preformed lithium and magnesium enolates in which one or both of the reaction partners are chiral. 

The major and minor products obtained in aldol reactions of chiral aldehyde (168 equation 109) are not those predicted by Cram s rule, presumably because the lithium cation is chelated by the alkoxy and aldehyde oxygens, leading to a rigid six-meml red intermediate that undergoes attack primarily from its unsubstituted face. " Similar behavior, with somewhat higher diastereofacial selectivity (5 1), is seen with the magnesium enolate (equation 50). 

Chiral acetate (204) shows excellent diastereofacial selectivity and has obvious utility as a reagent for asymmetric aldol reactions. As shown in equation (122), reaction of (204) with benzaldehyde provides diastereomers (205) and (206). As shown in Table 23, entry 1, the diastereoselectivity is 83% if the lithium enolate is formed in the conventional manner and the aldol reaction is carried out in THF at -78 C. A significant improvement is obtained by using the magnesium enolate (Table 23, entry 5), and diastereoselectivity of up to 98% is obtained by the use of very low reaction temperatures (Table 23, entries 10-13). 

One of the virtues of the Braun reagent is that both enantiomers are available, since the chiral diol is made by reaction of phenylmagnesium bromide with (/ )- or (5)-methylmandelate. An application of the (5)-enantiomer is shown in equation (123). The initial aldol reaction was carried out with the magnesium enolate in THF at -78 C to give the diastereomeric aldols in a ratio of 97 3. Transesterification with methanol gives -hydroxy ester (207) in 94% enantiomeric excess. 

As bases. Formation of magnesium enolates from a-chloro-a-arenesulfinylcar-boxylic acid derivatives involves desulfinylation with a Grignard reagent. f-Butyl Grignard reagents are preferred in certain circumstances for the deprotonation of carbon acids. This method has been applied to a synthesis of chiral jS-hydroxy esters from arenesulfinylacetic esters. ... 

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