Intramolecular Horner-Emmons

The remaining section highlights various other methods of generating piperidine cores. The scheme below depicts a simple route to piperidines heterocycles, such as 196, via an intramolecular Horner-Emmons cyclization of phosphonate 197 <06JA12743>. 

A-Ethyl(diethylphosphono)methylketenimine, readily prepared from the amide, is of value as an annelating reagent (79CC900). The sodium salt of salicylaldehyde reacts at the activated central carbon atom of the ketene and a subsequent intramolecular Horner-Emmons reaction results in cyclization to the chromene. 

The Michael-addition of l//-pyrrole-2-carbaldehyde 1311 to Cr(CO)3-complexed aryl allenylphosphonates 1312 followed by an intramolecular Horner-Emmons-Wadsworth olefmation in boiling THE gives rise to arene Cr(CO)3-substituted 3-(l-methylethylidene)-3//-pyrrolizines 1313 and 1314 in moderate to good yields (Scheme 251) <1998T1457>. 

The esterification of a 1,3-ketoaldehyde enol with a diethoxyphosphinylalkanoic acid, forming the ester linkage of the final molecule first, allows ring closure via an intramolecular Horner-Emmons reaction. ... 

In the initial period of our synthetic efforts on the construction of the A/B ring equivalents, we had prepared two functionalized tetrahydrofuran-3-ones 62 and 64 from 2 (Scheme 7). We experienced at that time much difficulty in the C7-C8 bond formation (the eremantholide numbering) by means of an intramolecular aldol (62 to 63) or an intramolecular Horner-Emmons (64 to 65) reaction. After throughout investigations examined using theses and related substrates, we finally abandoned the A/B ring construction by means of these base-mediated "polar" carbon-carbon bond forming reactions. 

Nicolaou s carbonolide synthesis is also based on the coupling of the C -Cio (172) and C11-C15 (174) segments, and the macrolactonization by the intramolecular Horner-Emmons reaction (Nicolaou method). 

The ester 169 was converted into 170 through a Michael type three-carbon extension. The carboxylic acid 172 was derived from 170 through the ketophos-phonate 171. The C11-C15 segment 174 was prepared from (R)-3-hydroxy-butyric acid (173). Esterification of 172 with 174 using DCC and DMAP gave 175, which was converted into 176 through an intramolecular Horner-Emmons reaction. The lactone 176 was transformed to the Tatsuta intermediate 163. 

Ring Closure by Intramolecular Horner-Emmons Reaction. 605... 

The coupling of 77 and 84 was performed via the Julia-Julia olefination [50] to construct the ( )-olefin 85 EjZ => 20) at the C14-C15 bond. This approach is slightly more efficient than that of the Kocienski-Julia protocol in the case of Lee s synthesis. As a macrocyclization, the intramolecular Horner-Emmons reaction was adopted, because macrolactonization of the hydroxy (E, )-dienylcarboxylic acid was difficult. The phosphonate 86, derived from 85, was exposed to K2CO3 and 18-crown-6 [51-53] to provide the macrolactone 87 in good yield. Finally, the side chain was introduced via the Wittig reaction like Lee s method, and the second total synthesis was accomplished. 

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