Masamune-Roush reaction

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. 

Masamune-Roush Modification of the Horner-Wadsworth-Emmons Reaction... 

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... 

As with all reactions with phosphonates, these conditions are sensitive to the steric environment of the carbonyl and phosphonate. In a reaction directed at intermediates for synthesis of the erythronolides, Paterson and cowoilcers found that the unsubstituted phosphonate (188) added in 82% yield in the presence of molecular sieves (equation 48). When R was methyl the reaction failed with DBU because of competitive elimination of OSiMe2Bu. Model studies with the phosphonate and isopropyl aldehyde were successful, providing the alkene in 78% yield in an ratio of 8 1. The Roush-Masamune... 

Blanchette, M. A., Choy, W., Davis, J. T., Essenfeld, A. P., Masamune, S., Roush, W. R., Sakai, T. Horner-Wadsworth-Emmons reaction use of lithium chloride and an amine for base-sensitive compounds. Tetrahedron Lett. 1984, 25, 2183-2186. 

This reaction has been modified to occur under mild conditions such as those of Masamune and Roush, Still, and Ando. In addition, chiral phosphonates (or phospho-namides) have been used for this reaction. In particular, the method developed by Still and Gennari using [bis(trifiuoroethyl)phosphono] esters, generally known as Gennari-Still phosphonates, is very useful in the preparation of Z-olefins. Illustrated is the HWE reaction using Gennari-Still phosphonates to give c/ -olefins, and its mechanism. 

Bases in combination with Lewis acids are powerful in promoting the HWE reaction with many substrates that are incompatible with strong bases. In 1984, Masamune and Roush et al. reported mild conditions using lithium chloride and DBU (or i-Pr2NEt) [172], and later Rathke et al. extended this Lewis acid/base system to lithium or magnesium halides with triethylamine [173]. Recently, Helquist et al. have employed Zn(OTf)2, TMEDA, and DBU to promote the HWE reaction of aldehydes with diethylphosphonoacetic acid to give a,p-unsaturated carboxylic acids with excellent selectivity [174]. 

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