250589-63-0Relevant articles and documents
Stereoconvergent synthesis of N-Boc-(2R,3S)-3-hydroxy-2-phenylpiperidine
Velasco, Manuel,Hernández, Ulises,Terán, Joel L.,Gnecco, Dino,Orea, María L.,Aparicio, David M.,Gómez-Calvario, Víctor,Bernès, Sylvain,Juárez, Jorge R.
, p. 820 - 824 (2019)
The stereoconvergent synthesis of N-Boc-(2R,3S)-3-hydroxy-2-phenylpiperidine from (R)-1-(2-((tert-butyldimethylsilyl)oxy)-1-phenylethyl)piperidin-2-one is described. The key steps involved are α-hydroxylation of quiral lactam with O2, stereoconvergent reduction of (R)- or (S)-3-(benzyloxy)-piperidin-2-one with Red-Al which afforded in both cases the trans-bicyclic oxazolidine in high stereoselectivity after chromatographic purification and a stereospecific Grignard addition to chiral bicyclic oxazolidine.
Catalytic Asymmetric Construction of Halogenated Stereogenic Carbon Centers by Direct Vinylogous Mannich-Type Reaction
Zhong, Feng,Yue, Wen-Jun,Zhang, Hai-Jun,Zhang, Cheng-Yuan,Yin, Liang
, p. 15170 - 15175 (2018)
A catalytic asymmetric vinylogous Mannich-type reaction of γ-halo-α,β-unsaturated N-acylpyrazoles and N-Boc-aldimines was disclosed, which afforded an array of halogenated (F-, Cl-, and Br-) allylic stereogenic carbon centers in high yields with good to high regio-, diastereo-, and enantioselectivities. The brominated product served as a suitable electrophile for common SN2 nucleophilic substitution and copper-mediated SN2′ allylic alkylation with metal reagents. The utility of present methodology was demonstrated by the asymmetric synthesis of a common intermediate toward the synthesis of two chiral 2,3-disubstituted piperidine pharmaceuticals.
Synthesis of 2-Arylpiperidines via pd-catalyzed arylation of aza-Achmatowicz rearrangement products with arylboronic acids
Zhao, Guodong,Canterbury, Daniel P.,Taylor, Alexandria P.,Cheng, Xiayun,Mikochik, Peter,Bagley, Scott W.,Tong, Rongbiao
, p. 458 - 463 (2020/01/21)
The first Pd-catalyzed arylation of aza-Achmatowicz rearrangement products with arylboronic acids is achieved, providing versatile 2-Aryldihydropyridinones for facile synthesis of highly functionalized 2-Arylpiperidines. Key to this arylation is the use of non-phosphine-ligand palladium precatalyst. The substrate scope is demonstrated with >26 examples, and the utility of 2-Aryldihydropyridinones is illustrated by the synthesis of a small collection of 2-Arylpiperidines with substituents or functional groups at any carbon (C2-C6) as well as two NK1 receptor antagonists (+)-CP-999,94 and (+)-L-733,060.
Stereoselective addition of Grignard reagents to sulfinimines derived from tartrate diol (threitol): Generation of chiral building blocks for the collective total synthesis of lentiginosine, conhydrine and methyldihydropalustramate
Prasad, Kavirayani R.,Rangari, Vipin Ashok
, (2019/08/20)
A systematic investigation of the addition of Grignard reagents to sulfinimines derived from tartaric acid diol was undertaken. It was observed that the chirality of the inherent tartrate moiety influences the diastereoselectivity of the resultant sulfinamides formed in the reaction. The formed products serve as excellent building blocks for the synthesis of natural products. This has been demonstrated in the collective total synthesis of lentiginosine, (+)-α-conhydrine and methyldihydropalustramate.
Preparation method of chiral ortho-amino alcohol intermediates, antagonists and analogues of antagonists
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Paragraph 0012, (2018/09/08)
The invention belongs to the field of chemical synthesis, relates to a preparation method of chiral ortho-amino alcohols and antagonists, and particularly relates to a preparation method of chiral ortho-amino alcohols and antagonists CP-122, 721 and L-733
Divergent syntheses of L-733, 060 and CP-122721 from functionalized pieridinones made by one-pot tandem cyclization
Liu, Yi-Wen,Mao, Zhuo-Ya,Ma, Rui-Jun,Yan, Jia-Hang,Si, Chang-Mei,Wei, Bang-Guo
, p. 2100 - 2108 (2017/03/17)
An efficient diastereoselective approach to access trans-5-hydroxy-6-substituted 2-piperidinones skeleton has been developed through one-pot intramolecular tandem process of O-benzyl protected aldimine 11 with Grignard reagents. The diastereoselectivity of substitution at C-6 position of 2-piperidinone was controlled by α-benzyloxy group. In addition, the utility of this straightforward cascade process is demonstrated by the asymmetric syntheses of (+)-L-733, 060 (2) and its 2-substituted analogue 3, as well as (+)-CP-122721 (5).
Highly enantioselective organocatalytic oxidative kinetic resolution of secondary alcohols using chiral alkoxyamines as precatalysts: Catalyst structure, active species, and substrate scope
Murakami, Keiichi,Sasano, Yusuke,Tomizawa, Masaki,Shibuya, Masatoshi,Kwon, Eunsang,Iwabuchi, Yoshiharu
, p. 17591 - 17600 (2015/02/19)
The development and characterization of enantioselective organocatalytic oxidative kinetic resolution (OKR) of racemic secondary alcohols using chiral alkoxyamines as precatalysts are described. A number of chiral alkoxyamines have been synthesized, and their structure-enantioselectivity correlation study in OKR has led us to identify a promising precatalyst, namely, 7-benzyl-3-n-butyl-4-oxa-5-azahomoadamantane, which affords various chiral aliphatic secondary alcohols (ee up to >99%, krel up to 296). In a mechanistic study, chlorine-containing oxoammonium species were identified as the active species generated in situ from the alkoxyamine precatalyst, and it was revealed that the chlorine atom is crucial for high reactivity and enantioselectivity. The present OKR is the first successful example applicable to various unactivated aliphatic secondary alcohols, including heterocyclic alcohols with high enantioselectivity, the synthetic application of which is demonstrated by the synthesis of a bioactive compound.
Concise, stereodivergent and highly stereoselective synthesis of cis-and trans-2-substituted 3-hydroxypiperidines-development of a phosphite-driven cyclodehydration
Huy, Peter H.,Westphal, Julia C.,Koskinen, Ari M.P.
, p. 369 - 383 (2014/03/21)
A concise (5 to 6 steps), stereodivergent, highly diastereoselective (dr up to >19:1 for both stereoisomers) and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, a core motif in numerous bioactive compounds, is presented. This sequence allowed an efficient synthesis of the NK-1 inhibitor L-733,060 in 8 steps. Additionally, a cyclodehydration-realizing simple triethylphosphite as a substitute for triphenylphosphine is developed. Here the stoichiometric oxidized P(V)-byproduct (triethylphosphate) is easily removed during the work up through saponification overcoming separation difficulties usually associated to triphenylphosphine oxide.
Efficient, stereodivergent access to 3-piperidinols by traceless P(OEt)3 cyclodehydration
Huy, Peter H.,Koskinen, Ari M. P.
, p. 5178 - 5181 (2013/11/06)
A stereodivergent and highly diastereoselective (dr up to >19:1 for both isomers), step economic (5-6 steps), and scalable synthesis (up to 14 g) of cis- and trans-2-substituted 3-piperidinols, the core motif of numerous bioactive compounds, providing efficient access to the NK-1 inhibitor L-733,060 is presented. Additionally, a "traceless" (referring to the simplified byproduct separation) cyclodehydration realizing simple P(OEt)3 as a substitute for PPh3 is developed.
Enantioselective ring expansion of prolinols: An efficient and short synthesis of 2-phenylpiperidin-3-ol derivatives and 3-hydroxypipecolic acids
Cochi, Anne,Burger, Benjamin,Navarro, Cristina,Pardo, Domingo Gomez,Cossy, Janine,Zhao, Yang,Cohen, Theodore
body text, p. 2157 - 2161 (2009/12/24)
A very short route to 2-phenylpiperidin-3-ol derivatives and 3-hydroxypipecolic acids is described. The approach uses two key steps: a one-pot reduction/Grignard addition sequence applied to alkyl proline esters and a ring expansion applied to the corresp
