Asymmetric Synthesis of Neolignans (−)-epi-Conocarpan and (+)-Conocarpan via Rh(II)-Catalyzed C−H Insertion Process and Revision of the Absolute Configuration of (−)-epi-Conocarpan

Abstract

The asymmetric C-H insertion of alkyldiazosulfones has been studied. High selectivity was achieved using a combination of a chiral catalyst and a chiral auxiliary (Rh2(S-pttl)4 and menthyl ester).

Catalytic asymmetric C–H insertion reactions of α-diazocarbonyl compounds

“…54 For this purpose, the newly developed rhodium(II) carboxylate complex Rh 2 (S-PTTEA) 4 was found to be the most advantageous catalyst choice, providing the desired cis isomer of 87 in 80% yield and 84% ee (Scheme 10). A similar synthetic strategy has been adopted by Fukuyama and coworkers for the total syntheses of the macrocyclic spermine alkaloid, (-)-ephedradine, 131,132 and the pentacyclic indole alkaloid, (-)-serotobenine.…”

“…3 These phthalimide catalysts (8a and 8b) displayed considerable enantioselectivity (up to 46% ee) and several related complexes were later prepared to include tert-leucinate [Rh 2 (S-PTTL) 4 ] 8e, valine [Rh 2 (S-PTV) 4 ] 8d, phenylglycine [Rh 2 (S-PTPG) 4 ] 8c and triethylalanine [Rh 2 (S-PTTEA) 4 ] 8f derived catalysts ( Figure 5), showing improvements in enantiocontrol in many cases, due to the increased steric bulk of the alkyl group of the ligand. 53,54 The related catalysts Rh 2 (S-NPV) 4 9a and Rh 2 (S-NPTL) 4 9b ( Figure 5) have also been developed by Chiu and co-workers, showing moderate enantioselectivity in the C-H insertion reactions of meso oxabicyclic compounds. Subsequent work by Hashimoto and co-workers has included the development of a series of catalysts featuring an extended phthalimido wall (Figure 6), namely, Rh 2 (S-BPTTL) 4 10d, Rh 2 (S-BPTA) 4 10a, Rh 2 (S-BPTPA) 4 10c, and Rh 2 (S-BPTV) 4 10b, derived from tert-leucine, alanine, phenylalanine, and valine, respectively.…”

Asymmetric Total Synthesis of (–)-trans-Blechnic Acid via Rhodium(II)-Catalyzed C–H Insertion and Palladium(II)-Catalyzed C–H Olefination Reactions

“…We envisaged that 1 would be accessible from an appropriately protected intermediate 11a, which would be derived from cis-2,3-dihydrobenzofuran 12 via Yu's C-H olefination process. On the basis of our previous work, 9,17 we expected that the intramolecular C-H insertion of aryldiazoacetate 13 using Rh 2 (R-PTTL) 4 (5c) or Rh 2 (R-PTTEA) 4 (5d) would provide cis-2,3-dihydrobenzofuran 12 with 2S,3R configuration. The requisite aryldiazoacetate 13 was prepared from the known 2-allyloxyphenol 14 23 as shown in Scheme 3.…”

“…Following an instructive precedent in the synthesis of 8, 17 we decided to protect the phenolic moiety at C2 as the TIPS ethers throughout the synthesis.…”

Catalytic enantioselective C–H functionalization of indoles with α-diazopropionates using chiral dirhodium(II) carboxylates: asymmetric synthesis of the (+)-α-methyl-3-indolylacetic acid fragment of acremoauxin A

“…Reagents and solvents were purified by standard means. Dehydrated CH 2 Cl 2 , THF and DMF were purchased from Kanto Chemical Co., Inc. Chiral dirhodium(II) carboxylates 1a-f 14a,17a,18a,21 and 2, 21 1-methoxymethylindole 5e, 39 1-methoxymethyl-5-nitroindole 5j 40 and -diazopropionates 6a, 23c 6b 41 and 6c 41 were prepared according to literature procedures.…”