Progress toward the Total Synthesis of Cassaine via the Transannular Diels−Alder Strategy

Abstract

The transannular Diels-Alder reaction of trans-trans-trans macrocyclic triene A, bearing two cis substiuents in C(12) and C(13) as well as a gem-dimethyl in C(4), was studied. Under thermal conditions, only the desired trans-anti-cis tricycle B was obtained. This tricycle represents an advanced intermediate toward the total synthesis of cassaine C.

A Cascade Cycloaddition Strategy Leading to the Total Synthesis of (−)-FR182877

“…Reduction to the corresponding aldehyde (DIBAL) was followed by a two carbon homologation (ethyl diazoacetate, SnCl 2 , 70 %, 2 steps)14 and selective removal of the TBDPS group ( n Bu 4 NF hydrate, HOAc, DMF, 92 %) to provide 13 15. Iodination of 13 (I 2 , PPh 3 ) gave a sensitive allyl iodide that was immediately submitted to macrocyclization conditions (Cs 2 CO 3 , THF, RT, 77 %, 2 steps) to give 14 as a 1:1 mixture of diastereomers, epimeric at C2 16. It was correctly anticipated that this intermediate, lacking the C2−C3 double bond, would not engage in a transannular Diels–Alder reaction.…”

Total synthesis of (+)-intricarene using a biogenetically patterned pathway from (−)-bipinnatin J, involving a novel transannular [5+2] (1,3-dipolar) cycloaddition

“…These functionalities would then be reacted, in sequence, with the stannane-substituted furfural 27, to elaborate bipinnatin J using sequential Stille cross coupling and NHK reactions. Thus, the a-phenylselanyl ester 23 was first prepared from the known allyl alcohol 22a, 23 following protection as the TBS ether 22b and phenylselanylation 24 of the carbanion derived from 22b. Further deprotonation of 23, using NaHMDS at -78 • C, followed by quenching the resulting carbanion with the epoxide 16 in the presence of BF 3 •OEt 2 next gave the adduct 24a as a mixture of diastereoisomers in 72% yield (Scheme 4).…”

“…(E )-7-(tert-Butyl-dimethyl-silanyloxy)-6-methyl-hept-5-enoic acid methyl ester 22b. t-Butyldimethylsilyl chloride (576 mg, 3.84 mmol) and imidazole (285 mg, 4.19 mmol) were added in one portion to a stirred solution of the alcohol 22a 23 (600 mg, 3.49 mmol) in DMF (1.8 ml) at 0 • C. The mixture was stirred at 0 • C for 10 mins and then diluted with ether. The ether solution mixture was washed with water (10 ml) and brine (5 ml), then dried (Na 2 SO 4 ) and concentrated in vacuo.…”

Total Synthesis of Cochleamycin A

“…Fragments 4 and 5 were joined via Stille coupling in 1:1 DMSO−THF in the presence of CuCl, which provided ( Z )-1,3-diene 21 in 85% yield (Scheme ). Several methods were explored for the cyclization of 21 to 22 , including Pd-catalyzed cyclization of the allyl carbonate derived from 21 , but the best results were obtained by using a Cs 2 CO 3 -mediated intramolecular alkylation of the derived allylic iodide, as pioneered by Deslongchamps . This reaction sequence provided macrocycle 22 as a 1:1 mixture of β-keto ester epimers together with ca.…”