A Stereoselective Approach to 1,3‐Amino Alcohols Protected as Cyclic Carbamates: Kinetic vs. Thermodynamic Control

Abstract

International audienceDirect enantiocontrolled access to 1,3-amino alcohols protected as cyclic carbamates is described. The approach is based on the addition of a silyl dienolate to aldehydes in the presence of 10 % of Carreira's catalyst (vinylogous Mukaiyama-aldol addition). The obtained -hydroxyesters were reduced to pent-2-ene-1,5-diols, which were converted into the corresponding dicarbamates with tosyl isocyanate. Stereoselective cyclization of these dicarbamates proceeded with 1,3-asymmetric induction under either thermodynamic or kinetic control to afford enantioselectively six-membered-ring cyclic carbamates. Calculations enabled us to rationalize the observed stereoselectivit

Modular synthesis of the pyrimidine core of the manzacidins by divergent Tsuji–Trost coupling

“…As shown in Scheme 3 , we next focused on the further derivatization of amine 12 towards suitably functionalized urea substrates 15 or 19 . Inspired by a work of Garcia [ 39 ], we initially intended to use isocyanate for both, the introduction of the urea motif and for the functionalization of the terminal homoallylic alcohol. Consequently, we evaluated the conversion of 14 to 15 .…”

“…As previously reported [ 31 ], this diastereodivergent coupling could indeed be realized as shown in Scheme 4 . Based on a report of Garcia for a related system we first evaluated Pd 2 (dba) 3 with different phosphite ligands [ 39 ]. However, the best results were obtained with the stable catalyst Pd(PPh 3 ) 4 and depending on the solvent used, either the syn -isomer 23 or the anti -isomer 24 could be selectively obtained.…”

O2‐Assisted Four‐Component Reaction of Vinyl Magnesium Bromide with Chiral N‐tert‐Butanesulfinyl Imines To Form syn‐1,3‐Amino Alcohols

“…[3] In this context, developing efficient approaches towards 1,3-amino alcohols in ad iastereo-and enantioselective manner has remained an active and important research area in organic synthesis.D iastereoselective access to 1,3amino alcohols typically involve reduction of 1,3-amino ketones, [4] 1,3-hydroxy imines [5] or 2,3-dihydroisoxazoles, [6] or the addition of organometallic reagents to 1,3-amino aldehydes and ketones (Scheme 1-I). [7] Palladium-catalyzed intramolecular allylic amination of N-tosyl carbamate, [8] hemiaminal [9] or trichloroacetimidates [10] derived from 2pentene-1,5-diol enables ac yclization strategy for the synthesis of 1,3-amino alcohol variants (Scheme 1-II). Recent elegant progresses in transition-metal-catalyzed aliphatic CÀ Ha mination [11] with nitrenes, [12] allylic CÀHa mination (Scheme 1-III) [13] and hydroamination of homoallenyl carbamate (Scheme 1-IV) [14] are emerging as straightforward and atom-economical route to this motif.…”

In situ tether formation from amines and alcohols enabling highly selective Tsuji–Trost allylation and olefin functionalization

“…More rarely, the in situ formation of the carbamate directly from the free alcohol has also been applied. 8 The use of carbon dioxide as tether precursor is even more challenging, and most success have been met for oxyhalogenation reactions. 9 A disadvantage of the use of carbonyls as tethers is that cleavage can require relatively harsh reaction conditions.…”