Weinreb s amide

The carbon-chain at the a-position on both adducts 33 and 35 was elongated by Arndt-Eistert sequence to provide the homologated esters 36 and 37. The esters 36 and 37 were transformed into the methyl ketones 40 and 41 via Weinreb s amides 38 and 39. 

Reaction of the organometallic species with Weinreb s amide ... 

The first total synthesis of the Stemona alkaloid (-)-tuberostemonine was accomplished by P. Wipf and co-workers. " The installation of the butyrolactone moiety commenced with the preparation of a Weinreb s amide from a methyl ester. The tricyclic methyl ester substrate was exposed to A/,0-dimethylhydroxylamine hydrochloride and Me2AICI and the tertiary amide was isolated in excellent yield. Next, the bromo ortho ester was treated with LDBB in THF to generate the corresponding primary alkyllithium species, which cleanly and efficiently added to the Weinreb s amide to afford the desired ketone. 

The preparation of the C1-C21 subunit of the protein phosphatase inhibitor tautomycin was completed by J.A. Marshall et al., and it constituted a formal total synthesis of the natural product. The spiroketal carbon of the target was introduced by the Weinreb ketone synthesis between a lithioalkyne and A/-methoxy-A/-methylurea (a carbon monoxide equivalent). The triple bond of the resulting Weinreb s amide was first reduced under catalytic hydrogenation conditions to yield the corresponding saturated amide, which was reacted with another lithium acetylide to afford an ynone. 

In the laboratory of E.J. Corey, the first synthesis of nicandrenones (NIC), a structurally complex steroid-derived family of natural products, was accomplished. The side chain of NIC-1 was constructed from the known six-membered lactone which was converted to the Weinreb s amide by treating it with excess MeNH(OMe) HCI and trimethyl-aluminum. The resulting primary alcohol was protected as the TBS ether. The ethynylation of this amide was carried out by reaction with two equivalents of lithium trimethylsilylacetylide to afford an ynone, which was reduced enantioselectively to the corresponding propargylic alcohol using CBS reduction. 

The rhodium-cataiyzed intramoiecuiar [5+2] cycioaddition of an allene and vinylcyclopropane was the key step in the asymmetric total synthesis of the trinorguaiane sesquiterpene (+)-dictamnol by P.A. Wender and co-workers.The cyclization precursor allene-cyclopropane was assembled starting from commercially available cyclopropane-carbaldehyde. Using the HWE oiefination, the Weinreb s amide moiety was installed and subsequently reacted with a primary alkyllithium that was generated via lithium-halogen exchange. 

Raghuram, T., Vijaysaradhi, S., Singh, I., Singh, J. Convenient conversion of acids to Weinreb s amides. Synth. Common. 1999, 29, 3215-3219. 

Weinreb s amide) as acylating reagent Nahm, S Weinreb, S. M. Tetrahedron Lett., 1981,22, 3815-3818. 

Synthetically the use of oxazolidinethione or thiazolidinethione auxiliaries offers the advantage that they are easily removed under mild conditions. Efficient reductive removal to give the diol is readily achieved in high yield with inexpensive and easily handle NaBILt. Alternatively the auxiliaries can be transformed into the versatile Weinreb s amide by simply stirring in the presence of imidazole and the hydroxylamine salt. Most importantly, direct conversion to the aldehyde using >Bu2AlH was achieved directly. ... 

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