2014
DOI: 10.3762/bjoc.10.35
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Concise, stereodivergent and highly stereoselective synthesis of cis- and trans-2-substituted 3-hydroxypiperidines – development of a phosphite-driven cyclodehydration

Abstract: SummaryA 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)-byprodu… Show more

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Cited by 18 publications
(6 citation statements)
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“…Stimulated by these preliminary results, we decided to carry out a deeper investigation of the reduction of enecarbamate 1a with hydride species in order to develop selective allylic reduction processes. , While sodium borohydride was totally ineffective, the use of the lithium analog (LiBH 4 ) afforded 2,3-dehydropiperidine 5a with complete regioselectivity in the attack of the hydride at the C 4 position (Scheme ). It should be noted that 3-oxygenated-2-aryl-piperidines such as 5a are compounds of considerable importance in medicinal chemistry …”
supporting
confidence: 76%
“…Stimulated by these preliminary results, we decided to carry out a deeper investigation of the reduction of enecarbamate 1a with hydride species in order to develop selective allylic reduction processes. , While sodium borohydride was totally ineffective, the use of the lithium analog (LiBH 4 ) afforded 2,3-dehydropiperidine 5a with complete regioselectivity in the attack of the hydride at the C 4 position (Scheme ). It should be noted that 3-oxygenated-2-aryl-piperidines such as 5a are compounds of considerable importance in medicinal chemistry …”
supporting
confidence: 76%
“…The results show that there is no solvation or polycrystalline transition during the measurement of solubility in different solvents. Furthermore, it is considered that the discrepancy with 1) Raw material of CbzLPG; equilibrated solid in (2) water, (3) ethanol, (4) isopropyl alcohol, (5) acetone, (6) acetonitrile, (7) methanol, (8) ethyl acetate, (9) dichloromethane, (10) n-propyl alcohol, (11) of absolute temperature and increases monotonously with the increase of temperature. The solubility of CbzLPG is the largest in acetone, and that in water is the lowest.…”
Section: T H Imentioning
confidence: 99%
“…The advantages of this method are as follows: on the one hand, the preparation of reagents and the introduction of protective groups are relatively easy; on the other hand, N -benzyloxycarbonyl amino acids and peptides are easy to crystallize and not easy to racemize during activation. N -carboxyphenoxy- L -2-phenylglycine (CbzLPG, shown in Figure and Table ) is an N -protected amino acid derivative of L -phenylglycine, which can be obtained by adding L -phenylglycine and carbonyl chloride to water in the alkaline condition of sodium hydroxide and stirring at room temperature. It exists as a white solid, and its melting point is 404.15 K, as reported by Angelova et al Despite the fascinating properties of phenylglycine derivatives, the structural and vibrational investigations on CbzLPG were carried out and discussed by Sathish et al in 2017 . The report on the solubility of CbzLPG was found to be not up to date.…”
Section: Introductionmentioning
confidence: 97%
“…The second oxidative addition and subsequent reduction of the double bond delivered piperidine 40 (Scheme 21). Interestingly, 2,3-disubstituted piperidine scaffolds (type 39) represent a pharmaceutically interesting molecular skeleton, since this motif is included into non-peptidic human neurokinin-1 (NK1) substance P receptor antagonists, natural products, antiprotozoal agent and potential chemotherapeutic agents [48][49][50]. The use of common reducing agents, with or without palladium catalysts, provided selectively ∆ 2,3 -or ∆ 3,4 -piperidine derivatives 41 and 42 with unconventional substitution patterns [45].…”
Section: Reductive Elaboration Of 142-dioxazinesmentioning
confidence: 99%