Rhodium(II)-Catalysed Intramolecular O-H Insertion of alpha-Diazo-gamma-Azido-delta-Hydroxy-beta-Ketoesters: Evidence for a Novel Sigmatropic Rearrangement of an Allylic Azide Intermediate

Abstract

3(2H)-Furanona-2-carboxilatos têm sido preparadas em bons rendimentos e seletividade moderada (d.e. ca 60%), a partir da reação de inserção de O-H intramolecular de δ-hidroxi-α-diazoésteres catalisada por Rh2(OAc)4. Observou-se que as furanonas 2,5-cis substituídas são formadas inicialmente na reação, sofrendo epimerização quando submetidas à cromatografia em sílica gel, fornecendo os isômeros 2,5-trans correspondentes. A decomposição de γ-azido-δ-hidroxi-α-diazoestéres catalisada por Rh2(OAc)4 também forneceu 3(2H)-furanona-2-carboxilatos. Estes compostos são formados a partir de transformações sequenciais, envolvendo primeiramente uma reação de inserção de O-H intramolecular, seguido de um rearranjo sigmatrópico concertado [3,3] do intermediário alil azida.The Rh2(OAc)4 catalyzed intramolecular O-H insertion reaction of δ-hydroxy-α-diazoesters affords 3(2H)-furanone-2-carboxylates in good yield but with moderate selectivity (d.e. ca 60%). The initially formed 2,5-substituted cis-furanones were found to epimerize to the corresponding 2,5-trans isomers when subjected to silica gel chromatography. The Rh2(OAc)4 catalyzed decomposition of γ-azido-δ-hydroxy-α-diazoesters also furnished 3(2H)-furanone-2-carboxylates. These compounds are derived by a sequential O-H insertion reaction followed by a concerted [3,3]-sigmatropic shift of the allylic azide intermediate.

In Vivo Antitumor Activity of Clitocine, an Exocyclic Amino Nucleoside Isolated from Lepista inversa

“…This support favored further anomerization, as the epimerization of 2,5-cis-substituted furanone to the respective trans isomer in silica gel has been reported. [16] Clitocine showed cytotoxic activities with IC 50 values in the sub-millimolar range on murine and human cancer cell lines. This pyrimidine compound exhibited greater potencies against 3LL and L1210 cells than doxorubicin, which was used as a positive control.…”

(2aR*,5S*,6aS*,8aS*,E)-Ethyl 5-hydroxy-7,7,8a-trimethyl-8-oxo-2,2a,6,6a,7,8,8a,8b-octahydro-1H-pentaleno[1,6-bc]oxepine-4-carboxylate

“…For rhodium carbenoid-mediated intermolecular O-H insertion reactions and their application to natural product synthesis, see: Paulissen et al (1973); Cox et al (1994); Haigh (1994); Aller et al (1995); Shi et al (1995); Bulugahapitiya et al (1997); Moody & Miller (1998); Nelson et al (2000); Medeiros & Wood (2010); Freeman et al (2010); Morton et al (2012). For rhodium-catalysed intramolecular O-H insertion reactions, see: Paulissen et al (1974); Moyer et al (1985); Moody & Taylor (1987); Heslin & Moody (1988); Davies et al (1990); Moody et al (1992); Sarabia-Garciá et al (1994); Padwa & Sá (1999); Im et al (2005). For reviews on rhodiummediated C-H insertion reactions, see: Doyle et al (2010); Davies & Morton (2011).…”

“…Hence the methodology has proven to be a useful stratagem in the synthetic acquisition of several natural products (Nelson et al, 2000;Medeiros & Wood, 2010;Freeman, et al 2010). While not as extensively utilized or studied as the intermolecular variants, intramolecular interception of rhodium carbenoids by hydroxy nucleophiles can, nevertheless, afford an effective route to cyclic ethers and lactones (Paulissen et al, 1974;Moyer et al, 1985;Moody & Taylor, 1987;Heslin & Moody, 1988;Moody et al 1992;Sarabia-García et al, 1994;Padwa & Sá, 1999;Im et al, 2005). Indeed, studies by Moody and co-workers have shown that rhodium(II) acetate catalysed cyclization in diazoalcohols may even be employed as a practical method for accessing medium-ring oxacycles -oxepanes, in particular, wherein interference from competing C-H insertion reactions do not appear to be significant (Heslin & Moody, 1988;Davies et al, 1990).…”

Compostos alfa-diazo carbonílicos: uma estratégia atraente para a síntese orgânica

“…Por exemplo, o composto diazo carbonílico 129 quando decomposto cataliticamente na presença de álcoois produz éteres (130) em excelentes rendimentos 31 . Nas reações intramoleculares a inserção no grupo O-H também ocorre facilmente e com alto rendimento, conforme exemplificado para os compostos diazo carbonílicos 131 84 e 133 85 (Esquema 30). Apesar das reações intermoleculares serem utilizadas para simples eterificações, as variações intramoleculares oferecem grande versatilidade para a síntese orgânica, que depende apenas da imaginação.…”