Sultam propionate

Besides their application in asymmetric alkylation, sultams can also be used as good chiral auxiliaries for asymmetric aldol reactions, and a / -product can be obtained with good selectivity. As can be seen in Scheme 3-14, reaction of the propionates derived from chiral auxiliary R -OH with LICA in THF affords the lithium enolates. Subsequent reaction with TBSC1 furnishes the 0-silyl ketene acetals 31, 33, and 35 with good yields.31 Upon reaction with TiCU complexes of an aldehyde, product /i-hydroxy carboxylates 32, 34, and 36 are obtained with high diastereoselectivity and good yield. Products from direct aldol reaction of the lithium enolate without conversion to the corresponding silyl ethers show no stereoselectivity.32... 

The control of the C8 stereocenter was achieved by alkylation directed by an auxiliary at C7 involving Oppolzer sultams, Enders hydrazones and Evans oxazolidinones (Scheme 5 l-IIl, resp.). Either the corresponding propionate [14, 37] or propionaldehyde [13, 16] equivalents were alkylated with an alkyl iodide representing the principal part of the northern half of epothilones (Scheme 5 1, II), or C-8 of a sui-table chain was methylated diastereoselec-tively (Scheme 5 III, IV). 

Related Reagents. (S)-4-Benzyl-2-oxazolidinone 10,2-Camphorsultam (/ )-(+)-f-Butyl 2-(p-Tolylsulfinyl)propionate 10-Dicyclohexylsulfonamidoisobomeol Diisopinocampheyl-boron Trifluoromethanesulfonate (R,R)-2,5-Dimethylborolane 2,6-Dimethylphenyl Propionate Ethyl 2-(Methyldiphenylsilyl)-propanoate a-Methyltoluene-2,a-sultam 3-Propionylthiazoli-dine-2-thione (/ ,/ )-1,2-Diphenyl-1,2-diaminoethane iV,iV -Bis-[3,5-bis(trifluoromethyl)benzenesulfonamide] 1,1,2-Triphenyl-1,2-ethanediol. 

Another classic in asymmetric synthesis is Oppolzer s sultam 91 [48], and various JV-acyl derivatives 92 were used - inter alia - for diastereoselective alkylations. Early attempts for enolate generation from amides 92 were plagued by competing deprotonation at carbon 10, adjacent to the sulfonyl group, but regioselective metallation at the a-carbonyl position was achieved by treatment with -butyllithium, LICA, or NaHMDS. The method is applicable not only to the sultam derived from propionic acid 92 (R = Me) but also to substituted and... 

Oppolzer s auxiliary opened, in addition, an access to a/iti-configured aldol adducts 272 (Scheme 4.62). For this purpose, silyl ketene N,0-acetal 271 was prepared from propionic sultam 92, obtained as a single diastereomer, according to the NMR spectra of the crude product, and isolated as a crystalline compound it was characterized as a cis-silicon enolate by a crystal structure analysis. For the subsequent Mukaiyama aldol addition, titanium tetrachloride was found to be the optimum Lewis acid to yield the awti-diastereomers 272 in excellent diastereoselectivity. Their formation under attack of the enolate to the Re-face of the aldehyde is consistent with an open transition state 275, wherein the Lewis acid-coordinated aldehyde is located on the face opposite to the sulfonyl group (Scheme 4.62) [136b]. An alternative approach to the a fi-aldol adducts was also elaborated, based upon cA-boron enolates 267 when they are reacted with aldehydes in the presence of titanium tetrachloride, an ti-selective aldol addition occurs leading to the products 272 rather than to sy -aldols 268 that result in the absence of the Lewis acid [136c]. 

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