Macrolactone Wittig coupling reaction

The completion of the total synthesis is described in Scheme 78. The Wittig reaction of 552 and 538 effected the coupling, and subsequent deprotection of TMS with KF afforded 41,42-dihydroxy carboxylic acid 553. Yamaguchi conditions effected macrolactonization of 553 in high yield and complete deprotection of the silyl groups afforded 4b and 554 in a ratio of 1 3. Treatment of (-)-23-epi-altohyrtin... 

Nicolaou et al. [143d] also reported the total synthesis of epothilone B (5b) via macrolactonization (Scheme 86). Aldol reaction of the lithium enolate of ketone 591 with aldehyde 590, prepared via Wittig reaction, yielded a 3 1 mixture of aldols. The desired isomer 592 was converted into carboxylic acid 593, which led to 5b. Because of the moderate and variable selectivities in the aldol coupling using ketone 591, they further investigated the reaction conditions. After extensive studies, the present reaction led to significant improvement of stereoselectivity (dr > 10 1) [143m]. 

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. 

Key steps (Figure 3.3, Scheme 3.2) in the Nicolaou synthesis of ABJ879 (10) are the formation of the C12-C13 double bond via a selective Wittig reaction between phosphorane 11 and aldehyde 12, the stereoselective aldol reaction of ot-chiral aldehyde 13 and ketone 14, macrolactonization of seco acid 16, stereoselective Sharpless epoxidation, to afford the C12-C13 epoxide, and introduction of the heterocycle by means of Stille coupling. ... 

---