Chlorotitanium enolates

The chlorotitanium enolate, generated by treatment of (S )-l-tm-butyldimethylsiloxy-l-cyclohexyl-2-butanone with titanium(iv) chloride and diisopropylethylamine, provides the syn-product upon reaction with benzaldehyde. The diastereoselectivity of 99 1 is defined as the ratio of the major isomer to the sum of all other isomers47bc. 

Substrate-induced diastereoselectivity is provided by the chlorotitanium enolate of 14a,b47b and the boron enolate of ketone 15S3 to give predominantly. wt-aldols. 

In a similar way. ft-keto imide 19 undergoes stereodivergenl aldol reactions. Thus, conversion of 19 into the tin enolate, and subsequent addition of aldehydes, give predominantly the diastereomers 20. On the other hand, hydroxy ketones 21 are the main products when the chlorotitanium enolate of 19 is reacted with aldehydes53. ... 

M. T. Bilodeau, Ph.D. Thesis I. Studies on the Direct Formation of Chlorotitanium Enolates. II. The Development of the Copper-Catalyzed Aziridination Reaction, Harvard University, Cambridge, MA, 1993. 

Highly diastereoselective acetate aldol additions using chlorotitanium enolates of mesityl-substituted JV-acetylthiazolidinethione 136 has been documented <07OL149>. These aldol reactions proceed in high yields and diastereoselectivities (94/6 to 98/2) for aliphatic, aromatic, and a,P-unsaturated aldehydes. Compound 136 also undergoes double diastereoselective aldol additions with chiral aldehyde 139 to give adduct 140 in high yields. 

The chlorotitanium enolates derived from AT-acyloxazolidinones 3.17, N-acyloxazolidinethiones 3.18 and iV-acylthiazolidinethiones 3.19 undergo highly selective and efficient aldol reactions with aldehydes. The iST-acyloxazolidinethione 3.18 and N-acylthiazolidinethione 3.19 auxiliaries are also easier to cleave. 

Phenylalanine-derived oxazolidinone has heen used in O Scheme 52 as a chiral auxiliary for as)rmmetric cross-aldolization (Evans-aldol reactions [277,278,279,280,281,282,283,284, 285]). The 6-deoxy-L-glucose derivative 155 has heen prepared by Crimmins and Long [286] starting with the condensation of acetaldehyde with the chlorotitanium enolate of O-methyl glycolyloxazohdinethione 150. A 5 1 mixture is obtained from which pure 151 is isolated by a single crystallization. After alcohol silylation and subsequent reductive removal of the amide, alcohol 152 is obtained. Swem oxidation of 152 and subsequent Homer-Wadsworth-Emmons olefination provides ene-ester 153. Sharpless asymmetric dihydroxylation provides diol 154 which was then converted into 155 (O Scheme 60) (see also [287]). 

The diastereoselective additions of chlorotitanium enolates of 7V-propionyl thiazolidinethione 133 to various metalloaldimines 134, available from hydrometallation of the corresponding nitriles, furnish a mixture of azetine 135 and tetrahydropyrimidinone 136 <04H(62)217>. Among the three hydrometallation methods evaluated, the hydrozirconation process proves to be the best in terms of the yield and selectivity. 

Enantioselective total synthesis of (+)-SCH 351448 has been completed recently by Crimmins and Vanier. Addition of acrolein to a solution of the chlorotitanium enolate of iV propionvl thiazolidinethione 95 provided the aldol adduct 98 in 97% yield (96% de). 

In the enantioselective total synthesis of Bistramide A, Crimmins and DeBaillie utilized their procedure for the synthesis of a key fragment 100. Exposure of the aldehyde to the chlorotitanium enolate of iV propionyl thiazolidinethione 99 proceeded smoothly with excellent diastereoselectivity... 

A highly diastereoselective synthesis of azetinyl thiazolidine-2-thiones has been achieved by addition of the chlorotitanium enolates of N-acyl thiazolidine-2-thiones to O-methyl aldoximes [103], where the antV azetines product can be subsequently converted to the corresponding P-amino carbonyl compounds with retention of stereochemistry (Scheme 14.35). 

An alternative to the boron-mediated aldol addition of oxazolidinone 210 was developed also by Evans and coworkers by using the direct formation of chlorotitanium enolates that were generated by treatment with titanium tetrachloride in the presence of Hiinig s base or TMEDA. The stereochemical... 

Evans DA, Reiger DL, Bilodeau MT, Urpi F. Stereoselective aldol reactions of chlorotitanium enolates. An efficient method for the assemblage of polypropionate-related synthons. 7. Affj. Chem. Soc. 1991 113(3) 1047-1049. 

Enolates of chiral carboximides linked to Evans or Oppolzer s auxiharies (+)- or ( )-Xcbo. -Xc -po and -Xcbs react with aldehydes, giving rise to syn a-branched /3-hydroxy carboxyhc acid derivatives (iyra-aldols) with excellent stereoselectivities, generally exceeding 96% and in chemical yields above 70% . Both boron enolates and chlorotitanium enolates have been used in isotopic synthesis. 

The normal yn-selectivity of (Z)-boron and chlorotitanium enolates can be overridden by diverting the cyclic transition state of the aldolization processes to an open one . This can be accomplished either by using (Z)-0-silyl-iV,0-ketene acetals as starting materials " or by treating the boron enolate solution with an aldehyde pre-complexed with a second Lewis acid 406,112,113 latter case, enantiopure 2-oxazolidinone-... 

Figure 11.52 Diastereoselective Michael addition of the chlorotitanium enolate of an Evans-type N-[1- C]acetyloxazolidin-2-one to a fi-nitrostyrene...

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