Towards EPC-syntheses of the structural class of cochleamycins and macquarimicins. Part 2: EPC-synthesis of the hydrindene subunit of the macquarimicins

A Formal Synthesis of (-)-Cephalotaxine

“…Regioselective rearrangement of the epoxide 15 using Yamamoto’s conditionsthen produced the allylic alcohol 16 in quantitative yield, and oxidation of 16 under Swern conditions finally afforded the desired enone 4 . Unfortunately, we were not able to effect the desired oxidative cleavage reaction of 4 to produce demethylcephalotaxinone ( 3 ) as the enone 4 proved to be quite unstable and spontaneously dimerized in solution to afford the endo hetero-Diels−Alder adduct 17 in a regio- and stereoselective manner (Scheme ) . As oxidative cleavage of 4 was not possible, a modified strategy for the completion of the synthesis was developed (Scheme ).…”

“…Unfortunately, we were not able to effect the desired oxidative cleavage reaction of 4 to produce demethylcephalotaxinone (3) as the enone 4 proved to be quite unstable and spontaneously dimerized in solution to afford the endo hetero-Diels-Alder adduct 17 in a regio-and stereoselective manner (Scheme 3). 14 As oxidative cleavage of 4 was not possible, a modified strategy for the completion of the synthesis was developed (Scheme 4). First, the secondary alcohol 16 was converted to the acetate 18, which was then exposed to 5% HCl (aq) to afford the primary alcohol 19 (Scheme 4).…”

Enantioselective Synthesis of the C1–C6 and C7–C23 Fragments of the Proposed Structure of Iriomoteolide 1a

“…Attempts to protect the free alcohol of 21 directly with TESOTf, TMSOTf, or TMSCl resulted in formation of the C11 mixed silyl ketal, wherein the silyl triflate or silyl chloride behaved as Lewis acids due to the crowded steric environment, rather than silylating agents as in similar systems. 23 Fortunately, the C14 tertiary alcohol of 17a could be protected as the TBS ether prior to the aldol addition to form 17b . Aldol reaction of ketone 17b and aldehyde 6 followed by treatment as before generated mixed ketal 22 .…”

“…The C11 exocyclic methylene proved challenging to install: attempts to install the C11 exocyclic olefin under standard methylenation conditions (Wittig, Tebbe, Tour, Takai–Nozaki) in the presence of the free tertiary alcohol at C14 ( 21 ) resulted in either elimination or no reaction, likely due to the presence of the free alcohol at C14. Attempts to protect the free alcohol of 21 directly with TESOTf, TMSOTf, or TMSCl resulted in formation of the C11 mixed silyl ketal, wherein the silyl triflate or silyl chloride behaved as Lewis acids due to the crowded steric environment, rather than silylating agents as in similar systems . Fortunately, the C14 tertiary alcohol of 17a could be protected as the TBS ether prior to the aldol addition to form 17b .…”