Gram Scale Synthesis of the C(18)−C(34) Fragment of Amphidinolide C

Abstract

An allylic cis-epoxide prepared by Sharpless asymmetric epoxidation was transformed in 9 steps and 41% overall yield to the cyclization precursor 4 via a key one carbon homologation. Cobalt catalyzed aerobic oxidative cyclization of 4 gave the trans-THF in 94% yield at gram scale. Subsequent manipulations, including a Still-Gennari olefination, Sharpless asymmetric dihydroxylation, Corey-Fuchs alkynylation and Kazmaier hydrostannylation provided the fully functionalized C(1)-C(9) fragment 2 suitable for cross coupling. The sequence is readily scalable and provides gram quantities of 2.

The impacts of climate change on local hydrology and low flow frequency in the Geum River Basin, Korea

“…We had initially planned to exploit Julia–Kocienski–Blakemore olefination20 of this aldehyde with the known PT sulfone;21 however, this reaction showed a preference for the undesired cis alkene. While alternate, multi‐step solutions have been developed to circumvent this problem,5c,j we continued to look for a direct solution. Fortunately, use of the Vedejs‐type tributyl phosphonium salt 36 22 cleanly generated desired E alkene 37 in good selectivity (97 % yield, E:Z =11:1).…”

Progress in the trans-Reduction and trans-Hydrometalation of Internal Alkynes. Applications to Natural Product Synthesis

“…A similar concept was pursued by Pagenkopf and Morran for the synthesis of the C18C34 fragment of the complex macrolide amphidinolide C ( Table 5, Entry 11). 131,134 Treatment of the 5-hydroxy-1,3-diyne 237 with Bu 3 SnH and a substoichiometric amount of triethylborane afforded a sensitive alkenyltin derivative which was transformed without delay into iodide 238; this compound, in turn, was subjected to a Stille coupling with Me 4 Sn. Interestingly, the key stannylation was highly selective for the alkyne moiety adjacent to the hydroxy group.…”

Asymmetric Total Synthesis of Inthomycins A, B, and C

“…Several asymmetric ynone reduction protocols, such as Noyori and Corey–Bakshi–Shibata (CBS) reductions, were examined for the installation of the stereocenter at the sterically hindered neopentyl position. The best enantioselectivity was obtained using DIPCl .…”