1383077-24-4

Upstream product

• 75844-69-8 t-butyl piperidinecarboxylate 
• 100-52-7 benzaldehyde 
• 138371-52-5 1,1-dimethylethyl 2-benzoyl-1-piperidinecarboxylate 

Relevant academic research and scientific papers

Catalyst-controlled diastereoselection in the hydrogenation of heterocycloalkyl ketones

α-Substituted chiral ketones that have small steric and electronic differences around the reaction sites are difficult substrates to reduce with high diastereoselectivity. Metal hydride reduction of 2-(4-benzoylmorpholinyl) phenyl ketone and 3-(1-tert-butoxycarbonylpiperidinyl) phenyl ketone using sodium borohydride, zinc borohydride, and potassium tri-sec-butylborohydride as reducing agents affords the syn- and anti-alcohols in a lower than 80:20 ratio. Hydrogenation of these ketones with a catalyst system of RuCl 2(BIPHEP)(DMEN) and potassium tert-butoxide in 2-propanol results in the syn-alcohols with ≥ 99:1 selectivity [BIPHEP=2,2′- bis(diphenylphosphino)biphenyl, DMEN=N,N-dimethylethylenediamine]. The marked difference in the diastereoselectivity suggests that the stereoselection in this hydrogenation is primarily regulated by the structure of the catalyst's reaction field ("catalyst-controlled diastereoselection") but not the internal stereocontrol of the substrates. This chemistry is applied to the asymmetric hydrogenation through dynamic kinetic resolution with a RuCl 2[(S)-BINAP][(R)-DMAPEN]/potassium tert-butoxide catalyst [BINAP=2,2′-bis(diphenylphosphino)-1,1′-binaphthyl, DMAPEN=2-dimethylamino-1-phenylethylamine]. A series of aryl heterocycloalkyl ketones has been converted to the alcohols in excellent diastereo- and enantioselectivities. The modes of catalyst-controlled diastereoselection and enantioselection are interpreted by using transition-state molecular models. (S,S)-Reboxetine, a selective norepinephrine uptake inhibitor, was synthesized from one of product alcohols. Copyright

Highly enantioselective catalytic dynamic resolution of N-boc-2-lithiopiperidine: Synthesis of (R)-(+)- N-boc-pipecolic acid, (S)-(-)-coniine, (S)-(+)-pelletierine, (+)-β-conhydrine, and (S)-(-)-ropivacaine and formal synthesis of (-)-lasubine II and (+)-cermizine C

The catalytic dynamic resolution (CDR) of rac-2-lithio-N-Boc-piperidine using chiral ligand 8 or its diastereomer 9 in the presence of TMEDA has led to the highly enantioselective syntheses of both enantiomers of 2-substituted piperidines using a wide range of electrophiles. The CDR has been applied to the synthesis of (R)- and (S)-pipecolic acid derivatives, (+)-β-conhydrine, (S)-(+)-pelletierine, and (S)-(-)-ropivacaine and the formal synthesis of ()-lasubine II and (+)-cermizine C.

Asymmetrie substitutions of 2-lithiated N-boc-piperidine and N-boc-azepine by dynamic resolution

Proton abstraction of N-tertbutoxycarbonyl-piperidine (N-Boc-piperidine) with sBuLi and TMEDA provides a racemic organolithium that can be resolved using a chiral ligand. The enantiomeric organolithiums can interconvert so that a dynamic resolution occurs. Two mechanisms for promoting enantioselectivity in the products are possible. Slow addition of an electrophile such as trimethylsilyl chloride allows dynamic resolution under kinetic control (DKR). This process occurs with high enantioselectivity and is successful by catalysis with substoichiometric chiral ligand (catalytic dynamic kinetic resolution). Alternatively, the two enantiomers of this organolithium can be resolved under thermodynamic control with good enantioselectivity (dynamic thermodynamic resolution, DTR). The best ligands found are based on chiral diamino-alkoxides. Using DTR, a variety of electrophiles can be used to provide an asymmetric synthesis of enantiomerically enriched 2-substituted piperidines, including (after Boc deprotection) the alkaloid (+)-ss-conhydrine. The chemistry was extended, albeit with lower yields, to the corresponding 2-substituted sevenmembered azepine ring derivatives.