Synthesis of Enantiopure 1‐Azaspiro[4.5]decanes by Iodoaminocyclization of Allylaminocyclohexanes

Abstract

The 5-endo iodine-promoted ring closure of 4-allyl-4-(alkylamino)cyclohexanone derivatives gives the corresponding 1-azaspiro[4.5]decanes in good yields. The reaction was tested with enantiopure homoallylamines to evaluate the diastereoselectivity of the process and to provide a route for pos-

Enantioselective Synthesis and Racemization of (−)‐Sinoracutine

“…Thea ddition of silver salts,w hich are routinely employed to facilitate analogous oxidations,w as not necessary,p robably due to neighboring group participation of the tertiary amine. [34,35] Elimination of TBS-OH under acidic conditions then gave tetracycle 11,w hose relative configuration was confirmed by an X-ray analysis of the racemic compound.…”

“…However, evaporation of the solvent, followed by dissolution of the intermediate in dimethyl sulfoxide and addition of triethylamine, delivered the α‐amino ketone 10 in good yield. The addition of silver salts, which are routinely employed to facilitate analogous oxidations, was not necessary, probably due to neighboring group participation of the tertiary amine . Elimination of TBS‐OH under acidic conditions then gave tetracycle 11 , whose relative configuration was confirmed by an X‐ray analysis of the racemic compound.…”

Enantioselektive Synthese und Racemisierung von (−)‐Sinoracutin

“…Das Intermediat erwies sich allerdings als instabil gegen wässrige Aufarbeitung, weshalb es nach Verdampfen des Lösungsmittels direkt in DMSO aufgenommen wurde; nach Versetzen mit NEt 3 wurde das α‐Aminoketon 10 in guter Ausbeute erhalten. Ein Versetzen mit Silbersalzen war hier nicht vonnöten, was wahrscheinlich auf den Nachbargruppeneffekt des tertiären Amins zurückzuführen ist . Säurevermittelte Eliminierung des TBS‐Ethers ergab die tetracyclische Struktur 11 , deren relative Konfiguration mithilfe von Kristallstrukturanalyse der racemischen Verbindung bestätigt wurde…”

Atom Transfer Radical Cyclization of Trichloroacetamides to Electron-Rich Acceptors Using Grubbs’ Catalysts: Synthesis of the Tricyclic Framework of FR901483

“…A solution of iodo derivative 6 (4.51 g, 10.9 mmol) in an aqueous solution of methylamine at 40% (50 mL) was heated in a sealed tube at 100 °C overnight. The mixture was extracted with CH 2 Cl 2 , and the organic extracts were dried and concentrated to yield the corresponding amine, which was used in the next step without further purification (3.4 g): 1 H NMR (300 MHz, CDCl 3 ) δ 1.45 (m, 1H), 1.54 (dd, J = 12.9, 5.7 Hz, 1H), 1.55 (m, 1H), 1.61–1.82 (m, 5H), 1.91 (td, J = 13.2, 4.2 Hz, 1H), 2.17–2.25 (dd, J = 12.9, 8.4 Hz, 1H), 2.31 (s, 3H), 2.55 (dd, J = 9.5, 4.5 Hz, 1H), 2.80 (dd, J = 9.5, 6.6 Hz, 1H), 3.11 (m, 1H), 3.54 and 3.69 (2d, J = 13.2 Hz, 1H each), 3.94 (s, 4H), 7.30 (m, 5H); 13 C NMR (75 MHz, CDCl 3 ) δ 28.8 (CH 2 ), 30.9 (CH 2 ), 32.4 (CH 2 ), 32.5 (CH 2 ), 34.6 (CH 3 ), 41.7 (CH 2 ), 51.8 (CH 2 ), 56.4 (CH 2 ), 56.7 (CH), 61.9 (C), 64.1 (CH 2 ), 108.4 (C), 126.3 (CH), 127.9 (CH), 128.0 (CH), 140.6 (C).…”

“…In the light of these previous results, a nonreductive process such as the ATRC studied here seemed a promising alternative to achieve the radical cyclization toward the diazatricyclic core of the natural product. The proradical trichloroacetamide required was prepared from azaspirodecane 6 , via carbamate 7 , following the transformations depicted in Scheme , with a final treatment of ketone 8 with isopropenyl acetate to yield a regioisomeric mixture of enol acetates 9 in a 1.8:1 ratio. When the nonseparated mixture of 9 was treated with G-2 at 155 °C for 2 h, the diazatricyclic derivative 10 and its epimer 11 were obtained in a 4.4:1 ratio and 54% overall yield, in addition to the unexpected epimeric mixture of enones 12 (Scheme ).…”