Ti-Catalyzed Cross-Cyclomagnesiation of 1,2-Dienes in the Total Z,Z,Z-Stereoselective Synthesis of Natural Acetogenin–Chatenaytrienin-1

Abstract

The first total synthesis of natural acetogenin, chatenaytrienin-1, was performed in 10 steps and in 41% overall yield using cross-cyclomagnesiation of (6 Z )-heptadeca-1,2,6-triene and trideca-11,12-dien-1-ol tetrahydropyran acetal with EtMgBr in the presence of Mg metal and the Cp 2 TiCl 2 catalyst (10 mol %) as the key step of the synthesis.

Total Synthesis of Chatenaytrienins-1, -3 and -4 and Muridienins-1–4 Enabled by C(sp)–C(sp3) Sonogashira Coupling

“…The spectroscopic and analytical data of all chatenaytrienins-1, -3 and -4 were in well agreement to that reported in the literature. 11,12 Scheme 4 Completion of the total synthesis of chatenaytrienins-1, -3 and -4.…”

“…[] D 25 = +13.8 (c = 0.7, CHCl 3 ) [Lit. 12 1 H NMR (500 MHz, CDCl 3 ):  = 6.97 (d, J = 1.6 Hz, 1 H), 5.47-5.28 (m, 6 H), 4.99 (qd, J = 6.7, 1.7 Hz, 1 H), 2.26 (t, J = 8.1 Hz, 2 H), 2.14-1.94 (m, 12 H), 1.54 (quin, J = 7.9 Hz, 2 H), 1.40 (d, J = 6.7 Hz, 3 H), 1.29-1.24 (m, 30 H), 0.87 (t, J = 6.8 Hz, 3 H). 13 C{H} NMR (100 MHz, CDCl 3 ):  = 173.9, 148.8, 134.4, 130.…”

“…The spectroscopic and analytical data of the prepared chatenaytrienins-1, -3 and -4 were in good agreement with those reported in the literature. 11,12 For the synthesis of muridienins-1-4 (3a-d), the intermediate enynes were prepared as shown in Scheme 5. Alcohols 17, 18 and 19 were subjected to Swern oxidation to give the corresponding aldehydes and subsequent Wittig olefination with phosphonium salt 34 afforded Z-selectively enynes 9, 10 and 11 in 81%, 83% and 80% yields, respectively, as the major products (9, E/Z = 6:94; 10, E/Z = 5:95; 11 E/Z = 6:94).…”

“…The spectroscopic and analytical data of the prepared chatenaytrienins-1, -3 and -4 were in good agreement with those reported in the literature. 11 12…”

“…Their synthesis involved Ti-catalyzed cross-cyclomagnesiation of 1,2-dienes as a key step. 12 Recently, in 2019, our group reported the first protecting-group-free total synthesis of chatenaytrienin-2 ( 2b ) in 7 steps and 36.5% overall yield. 13 Muridienins-1–4 ( 3a – d ) are linear non-THF/THP (non-hydroxylated) acetogenins containing a 1,5-diene moiety with exclusive cis -configured double bonds (Figure 1 ).…”