Natural products trichloroacetimidates

Deoxy-P-glycosides are important structural components of many natural products. Recently, 2-deoxy-2-iodoglycosyl trichloroacetimidates [469] have proved to be... 

Scheme 3.52), whereas the corresponding acetyl-protected donor gave little product under the same reaction conditions [512], Additionally, the trichloroacetimidate method has also been applied to synthesize other natural products, such as bupres-tin A and B [517], macrophylloside D [518] and neomycin mimetics [519]. 

Allyl alcohols readily react with trichloroacetonitrile to give the corresponding trichloroacetimidates 145. Activation of the double bond with electrophilic reagents results in ring closure to yield oxazolines 146. The most commonly employed electrophiles include iodine, iodine monochloride, phenylselenyl chloride, and mercuric trifluoroacetate. Other nitriles including cyanogen bromide and N,N-dimethylcyanamide can also be used. Since oxazolines readily hydrolyze to amides, the net effect of this reaction sequence is to produce p-amino alcohols 147 from an allyl alcohol. This strategy has been employed in numerous total syntheses of natural products. Examples are listed in Table 8.18 (Fig. 8.7 Scheme 8.43). ° ... 

Glucolipsin A (21) is a macrocyclic dilactone natural product that exhibits glucokinase-activating properties. Fiirstner et al. employed an Evans aldol strategy to synthesize the syn -aldol intermediate 2310 (Scheme 2.1j). The aldol reaction of the boron enolate of 14 with 14-methylpentadecanal (22) delivered the yyn-aldol product 23 in essentially diastereomerically pure form (99% de) after purification. Subsequent glycosidation of the alcohol 23 with trichloroacetimidate (24) was facilitated by catalytic amounts of TMSOTf (20 mol %) to afford the key intermediate (25) in moderate yield. 

The base-catalyzed addition of alcohols to nitriles to give imidates proceeds well, if there are electron-attracting groups in the a-position. In such cases the Pinner synthesis is less effective, because nitrile basicity is less. TTiis shows that both methods are complementary. Recently attention has been paid to the long-known addition of alcohols to trichloroacetonitrile, since it was found that imidates prepared from protected saccharides, amino alcohols etc. and trichloroacetonitrile are useful reagents for the synthesis of nucleosides, disaccharides and other natural products. The trichloroacetimidic acid esters (240 equation 131) of fluorinated, unsaturated aliphatic alcohols °° and benzyl alcohol have been prepared for synthetic purposes. 

Related to this methodology is another one recently developed by Kirsch et al. [61], in which (Z)-aUylic alcohols are first converted into their trichloroacetimidates, and the latter are then subjected to a catalytic Sj 2 substitution of the trichloroace-timidate by a carboxylate group under the influence of complex 132, available in both enantiomeric forms (Scheme 2.26). If a p,y-unsaturated acid is used, an allyl P,y-unsaturated ester is obtained, which, after RCM and base-catalyzed migration of the double bond, affords a 5,6-dihydro-a-pyrone. The authors demonstrated the practical applicabihty of this methodology with the synthesis of (-)-rugulactone and other natural products. 

Overman s discovery of the rearrangement of trichloroacetimidates [16, 39, 40] ushered in a powerful new method for the synthesis of alkaloids. A clever implementation of this transformation was reported in Danishefsky s synthesis of the antitumor agent pancratistatin (86, Scheme 16.9) [70]. Thermal rearrangement of imidate 84 led to amide 85, hence installing the key amine to become part of the lactam in the natural product and setting the stage for a subsequent diastereoselective dihydroxylation. 

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