Wadsworth-Emmons-Homer reduction

The ether derivatives 0,0,0-trimethylkorupensamine A (248) and B have both been synthesised by a route which commenced with a lengthy sequence to the biaryl 249 from 3,5-dimethylanisole (ref. 95) (Scheme 32). Reduction of 249 with LiAlHa and oxidation gave aldehyde 250 which upon Wadsworth-Emmons-Homer extension, reduction and Sharpless asymmetric epoxidation provided epoxide 251 and the corresponding atropisomer in almost equal amounts which were separated by silica gel chromatography. The derived alcohol 252, obtained by mesylation of 251 and in situ reduction, was then converted into the acetamide 253 by displacement with azide under Mitsunobu conditions followed by reduction and acetylation. Ring closure followed by stereoselective reduction then yielded 0,0,0-trimethylkorupensamine A (248). The synthesis of 0,0,0-triraethylkorupensamine B was accomplished in a similar manner using the atropisomer of 251 obtained in the epoxidation step. 

The first steps of the [ C]squalene synthesis resemble the pathway selected for the synthesis on [3 - C]coenzyme QIO 13061 (Figure 6.84). In this case alkylation with solanesyl bromide (3011 and subsequent hydrolysis and decarboxylation of the ester function converted ethyl [3- C]acetoacetate into [2- C]solanesylacetone 302. Chain extension of 302 in a Homer-Wadsworth-Emmons reaction, reduction of the resulting a,/3-unsatu-rated ester 303 and coupling of the resulting alcohol ([3- C]decaprenol, 3041 to 2-methyl-5,6-dimethoxy-1,4-hydroquinone (3051 provided the coenzyme in an overall radiochemical yield of 8% after oxidation. Methodologically comparable pathways have also been published for the synthesis of [5- C]farnesylacetic acid and [3 - C]menaquinone . 

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]). 

Similarly, the a-monochlorinated and a-monobrominated dimethyl 2-oxoalkylphosphonates are prepared in satisfactory yields (50%) by reaction of the sodium enolate of dimethyl 2-oxoalkyl-phosphonates with NCS or NBS in DME at room temperature- "- - or with bromine in Et20 (53-71%) or THE (60%) Synthesis of diethyl l-chloro-2-oxopropylphosphonate has also been reported through reduction of the 1,1-dichloro derivatives with sodium sulfite.- lodination in the Y-position of P-ketophosphonate 1,3-dianions prepared with KiCO, in MeOH has been reported. These dianions react with benzaldehyde in a Homer-Wadsworth-Emmons-Darzens reaction sequence to produce the a,P-unsaturated a, P -epoxyketones in 60-79% yields (Scheme 7.101).s ... 

The rest of the synthesis of pumiliotoxin is straightforward involving a Homer-Wadsworth-Emmons olefination (chapter 15) and a hydrogenation that accomplishes reductive animation and the control of another chiral centre. This synthesis is also discussed in chapter 21. 

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