Reaction of α-(N-Carbamoyl)alkylcuprates with Propargyl Substrates:  Synthetic Route to α-Amino Allenes and Δ³-Pyrrolines

Abstract

[reaction: see text] Carbamate deprotonation followed by treatment with CuCN.2LiCl affords alpha-(N-carbamoyl)alkylcuprates which react with propargyl halides, mesylates, tosylates, phosphates, acetates, and epoxides to give alpha-(N-carbamoyl) allenes via an anti-S(N)2' substitution process. Propargyl halides, sulfonates, and phosphates give good yields of carbamoyl allenes, while the acetates afford low yields. Propargyl substrates undergo regiospecific S(N)2' substitution in the absence of severe steric hindrance. The alpha-(N-carbamoyl) allenes can be cyclized to 2-oxazolidinones or deprotected to afford the free amines which can be cyclized to Delta(3)-pyrrolines with either AgNO(3) or Ru(3)(CO)(12).

Direct sp3C–H bond activation adjacent to nitrogen in heterocycles

“…This methodology has also proven to be an effective method to a-aminoallenes such as 65, which have recently been transformed into D 3 -pyrrolines in good yield using AgNO 3 or Ru 3 (CO) 12 . 20 Dieter's demonstration that vinyl iodides can be coupled in an enantioselective manner to produce products 57-59 has been recently utilized in the synthesis of a variety of natural products including (2)-pyrrolam A (68), 21 pyrrolizidine and indolizidine alkaloids 73-75, 22 and (+)-elaeokanine A (78, Scheme 5). 23 Although transmetalation with copper did allow reaction with coupling partners that were not compatible with a-aminoorganolithium reagent 28, the enantioselective variants of this methodology did not have enantiomeric ratios that were equivalent to those observed in Scheme 2, which suggests that the organocuprate may still be configurationally labile, albeit much less so than 28.…”

Transition metals in organic synthesis: Highlights for the year 2005

“…Platinum-catalyzed intramolecular hydroaminations of pendant alkenes to give five-or six-membered rings [1329]. Silver and ruthenium catalyzed intramolecular hydroaminations of 1-amino-3,4-dienes to give 2,5-dihydropyrroles [1330]. A silver-catalyzed intramolecular alkyne hydroamination was used in a synthesis of (+)-pseudodistomin D [294].…”

Direct Access to Functionalized Azepanes by Cross-Coupling with α-Halo Eneformamides

“…23 Furthermore, the availability of saturated N -acyl-2-alkynyl heterocycles is somewhat limited partly because α-lithiation followed by copper-mediated “alkynylation” often affords the allene. 24 However, using our strategy, an N -acyl iminium reduction of 22 affords alkyne 38 .…”