Masamune—Roush conditions

The sulfone moiety was reductively removed and the TBS ether was cleaved chemoselectively in the presence of a TPS ether to afford a primary alcohol (Scheme 13). The alcohol was transformed into the corresponding bromide that served as alkylating agent for the deprotonated ethyl 2-(di-ethylphosphono)propionate. Bromination and phosphonate alkylation were performed in a one-pot procedure [33]. The TPS protecting group was removed and the alcohol was then oxidized to afford the aldehyde 68 [42]. An intramolecular HWE reaction under Masamune-Roush conditions provided a macrocycle as a mixture of double bond isomers [43]. The ElZ isomers were separated after the reduction of the a, -unsaturated ester to the allylic alcohol 84. Deprotection of the tertiary alcohol and protection of the prima-... 

See also the Masamune-Roush conditions for this reaction. Generally useful for base-sensitive aldehydes. 

Cyclization via intramolecular olefination of complex phosphonates remains the most important method of synthesis for complex natural macrocycles. Examples include syntheses of 20-membered macrolide antibiotic, aglycones of venturicidins A and B,108 oleandomycin (a 14-membered macrolide antibiotic), 109 the 19-membered macrocyclic antibiotic, anti-tumour agent (-t-)-hitachimycin,ll0 and the macrocyclic lactones (183).1H Cyclization of the phosphonate (184) under Masamune-Roush conditions has been used to synthesize the 28-membered macrolactam myxovirescin B.112... 

The intramolecular HWE reaction in the presence of DBU was employed for the synthesis of (+)-rhizoxin D (71) by Jiang et al. [17]. Reaction of the aldehyde 69 with DBU-LiCl (Masamune-Roush conditions) [ 18] in acetonitrile at room temperature under high dilution conditions constructed the C2—C3 bond to form the macrolactone 70 (Scheme 7.14). Further elongation of the C20—C21 bond achieved the total synthesis of 71. 

A guanidine base has also been used for intramolecular HWE reaction. Nicolaou et al. reported a synthetic study of the originally proposed structure of diazonamide A (74) [19], employing the modified Masamune-Roush conditions [18]. Thus, reaction of aldehyde 72 with TMG (3)-LiCl in DMF at 70 °C generated 73 as a single atropisomer in 55-60% yield. Under other reaction conditions, for example, LHMDS in THE or DBU-LiCl in acetonitrile, 73 was obtained in only 0 35% yield (Scheme 7.15). Unfortunately, this advanced intermediate could not be transformed to the final product 74, because the C29-30 olefin was resistant to oxidation. 

Masamune-Roush conditions for the Horner-Emmons reaction... 

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