A Catalytic Asymmetric Synthesis of Polysubstituted Piperidines Using a Rhodium(I)‐Catalyzed [2+2+2] Cycloaddition Employing a Cleavable Tether

Abstract

An enantioselective rhodium (I) catalyzed [2+2+2] cycloaddition with a cleavable tether has been developed. The reaction proceeds with a variety of alkyne substrates in good yield and high enantioselectivity. Upon reduction of the vinylogous amide in high diastereoselectivity (>19:1) and cleavage of the tether, N-methylpiperidine products with functional group handles can be accessed.

Alkenes in [2+2+2] Cycloadditions

“…By using ac leavable tether,t his synthesis can give polysubstituted piperidines 4 upon further reduction (Scheme 27, entries 12, 13). [55] Iridium complexes have been less utilized, as their performance is similar to those of rhodium. However,l ower yields are generally obteined.…”

“…The indolizidinone cycloadducts formed included an aza‐quaternary stereocenter and enantioselectivities were excellent (Scheme , entries 6–10). By using a cleavable tether, this synthesis can give polysubstituted piperidines 4 upon further reduction (Scheme , entries 12, 13) …”

Application of the Curtius rearrangement to the synthesis of 1′-aminoferrocene-1-carboxylic acid derivatives

“…[70][71][72][73] They can also be used in cycloaddition or electrocyclization. [74][75][76][77][78][79] Introduced in 1972 by Yamada, the use of diphenylphosphoryl azide (DPPA) allows ester activation, azidation and Curtius rearrangement to be easily done in one-pot, facilitating the access towards isocyanates. 80,81 However, its use for the desymmetrization of bis-carboxylic acid carbocycles has been scarcely reported.…”

Rhodium(III)‐Catalyzed Oxidative Intramolecular 1,1‐Oxyamination of Alkenes with Protected Amino Acids to Produce Oxazoloisoindole‐2,5‐diones

“…First, Cp E Rh III acetate E, generated from [Cp E RhCl 2 ] 2 and Cu(OAc) 2 , reacts with 2 a to form five-membered rhodacycle C [rhoda(III) oxazolidine] via carboxylic acid-directed NÀ H bond cleavage. Subsequent alkene insertion gives seven-membered rhodacycle D. [16] β-Hydrogen elimination affords rhodium(III) hydride F and reductive elimination affords enamine G (path A). Protonation of the enamine moiety with the carboxylic acid affords zwitterionic intermediate H and the subsequent oxycyclization affords syn-product 3 a.…”