Synthesis of 2‐Azabicyclo[4.1.0]heptanes through Stereoselective Cyclopropanation Reactions

Abstract

Unsaturated δ‐lactams are cyclopropanated with the aid of diazo compound decomposition catalysed by metal complexes. A study of the reaction conditions, stereochemical outcome and group protection is reported. The resulting bicyclic products are related to bioactive compounds. Transformation into thiolactams facilitates the separation of the different isomers obtained and the removal of the protecting group. The cyclopropanation reaction works with diverse diazo compounds.

The Reactivity of Enantiopure (S)‐6‐Oxopipecolic Acid and Corresponding Pyridoisoquinolines Under Acidic Conditions

“…See the Supporting Information for NMR signal assignment. Spectral data of 15 were consistent with data reported in the literature …”

“…As we expected, all these pyridinone systems 12 , 15 and 16 could be independently prepared univocally from easily available 1‐benzyl‐6‐hydroxypiperidin‐2‐one ( 18 ) as the precursor of N ‐acyliminium intermediate Q (Scheme and Scheme ). Along this line, the requisite 1‐benzyl‐6‐hydroxypiperidin‐2‐one ( 18 ) was prepared in three steps starting from glutaric anhydride, by chemoselective DIBAL‐H reduction of N ‐benzyl glutarimide ( 17 ) as the key and earliest step of the sequence . Next, we tested the reaction under acidic conditions with different reagents enabling the selective transformation of starting hydroxyl lactam 18 to lactams 12 , 15 and 16 .…”

“…Along this line, the requisite 1-benzyl-6-hydroxypiperidin-2-one (18) [37] was prepared in three steps starting from glutaric anhydride, by chemoselective DIBAL-H reduction of N-benzyl glutarimide (17) as the key and earliest step of the sequence. [38] Next, we tested the reaction under acidic conditions with different reagents enabling the selective transformation of starting hydroxyl lactam 18 to lactams 12, 15 and 16. After careful checking of the reaction conditions, we have found that depending on the temperature, the use of TFA and TFAA, respectively, it afforded in good yields lactam 15 as well as trifluoroacetyl derivative 16 as was reported.…”

“…Recrystallization from n ‐pentane gave olefin 15 (266 mg, 71 % yield) as colorless crystals; m.p. 41.6–42.3 °C (reported as colorless oil) . R f = 0.68 (CH 2 Cl 2 / i PrOH; 10:1).…”

Generation of C2F5CHN2 In Situ and Its First Reaction: [3+2] Cycloaddition with Alkenes

“…I believe that, with this practical generation procedure, scientists will soon explore C 2 F 5 CHN 2 in other chemical reactions (e.g. cyclopropanation, carbene insertion, cycloaddition with alkynes) and its use will become as prominent as other diazoalkanes, such as CH 2 N 2 , [29] CF 3 CHN 2 , [21,22,30,31] and N 2 CHCO 2 Et. [32] Experimental Section General procedure Sodium nitrite (33 mg, 0.48 mmol, 3.0 equiv) was added at 0 8C to a stirring suspension of C 2 F 5 CH 2 NH 2 ·HCl (45 mg, 0.24 mmol, 1.5 equiv) in CH 2 Cl 2 (2.0 mL)/water (0.1 mL).…”