Short Enantioselective Total Syntheses of the Piperidine Alkaloids (S)-Coniine and (2R,6R)-trans-Solenopsin A via Catalytic Asymmetric Imine Hydrosilylation

Reding, Matthew T.; Buchwald, Stephen L.

doi:10.1021/jo980808q

Cited by 78 publications

(35 citation statements)

References 38 publications

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“…This method proved to be especially effi cient with imines derived from dialkyl ketones and unsaturated ketones. Applications in asymmetric synthesis soon followed through the synthesis of calcitemic compound (22) [14] and piperidine alkaloids (23) and (24) (Figure 13.3 ) [15] .…”

Section: Titanium-based Catalysts 325mentioning

confidence: 99%

Hydrosilylation of Imines

Riant¹

2008

Modern Reduction Methods

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13 IntroductionThe fi rst examples of the production of chiral secondary alcohols and amines by the reduction of a carbonyl or imino group using a silane as a reducing agent and a transition metal catalyst was reported during the mid 1970s by Kagan [1] . Following this fi rst report, the literature showed a growing interest in the discovery of effi cient catalytic systems for the hydrosilylation of ketones and aldehydes, while imines only started to show signifi cant advances much later . One of the main reasons is that most of the effi cient catalytic systems for the reduction of ketones were rhodium -based catalysts that usually required activated silanes such as bisaryl silanes. While these systems were active under very mild conditions, they suffered from strong economic drawbacks due to the cost of the catalysts, relatively poor catalytic effi ciency compared to hydrogenation and the cost of the silanes. Imines being poorer substrates than aldehydes and ketones suffered even more from these limitations and were neglected as substrates for hydrosilylation reactions until more effi cient systems were discovered during the 1990s. Indeed, imines are less electrophilic substrates compared to their carbonyl counterparts and are also susceptible to isomerization to enamines , when they posses one or more α -hydrogen. It is, however, possible to increase the electrophilic character of the imino group by the introduction of an aryl or an electron -withdrawing group on the nitrogen. The most common activating groups are tosyl, Boc or diphenylphosphinoyl. However, it is usually considered that only diphenylphosphinoyl combines ease of synthesis, stability to moisture and simplicity of removal for further transformations in synthesis. When designing a chiral catalyst for enantioselective addition of a nucleophile on an aldimine or a ketimine, another diffi culty arises from the possible cis -trans isomerization of the C = N double bond.However, nucleophilic addition to imines remains an attractive method for the synthesis of amines and increasing numbers of examples in the fi eld of asymmetric catalysis have been reported during the since the 1990s [2] . Concerning reduction processes, the costs of the catalytic systems and the silanes have often drawn chemists to develop more economic alternatives, such as hydrogenation.

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Section: Titanium-based Catalysts 325mentioning

confidence: 99%

Hydrosilylation of Imines

Riant¹

2008

Modern Reduction Methods

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“…The starting material 6 27 was prepared by Wittig methylenation of 8-chlorooctan-4-one, 28 which was obtained from commercially available 5-chlorovaleronitrile by addition of n-propylmagnesium chloride and further hydrolysis, following literature procedures.…”

Section: Resultsmentioning

confidence: 99%

“…t, J¼6.4 Hz, 1H, CHOH), 7.28 (m, 5H, ArH); d C24.Preparation of compound 6. Preparation of 8-chlorooctan-4-one 28. To a solution of n-propylmagnesium chloride (2.0 M in diethyl ether, 15 mL, 30 mmol) in dry diethyl ether (15 mL) under argon atmosphere was added 5-chlorovaleronitrile (3.5 mL, 30 mmol), dropwise, via syringe.…”

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confidence: 99%

Intramolecular carbolithiation promoted by a DTBB-catalysed chlorine–lithium exchange

2003

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“…The methodology has been applied in the synthesis of a number of optically active secondary amines such as (S)coniine, (2R,6R)-trans-solenopsin A [63] and a calcimimetic compound NPS R-568 [64]. An efficient kinetic resolution of 4-substituted tetralones, the pharmacophore of the important antidepressant sertraline, has also been achieved (Fig.…”

Section: Hydrosilylationmentioning

confidence: 99%

Recent Advances in Catalytic Asymmetric Addition to Imines and Related C=N Systems

Vilaivan¹,

Bhanthumnavin²,

Sritana-anant

2005

COC

150

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Addition reactions to imines are relatively less developed compared to those of carbonyl compounds due to low electrophilicity and ease of α-deprotonation. With the use of an appropriate activator, which can coordinate to the imine nitrogen atom, the electrophilicity of the imine can be enhanced and a range of nucleophilic addition reactions becomes possible. When the activator is chiral, it will also create chiral environment and will direct the approach of the nucleophile to one face of the imine over the other resulting in enantioselectivity. The potential of catalytic asymmetric addition to imines in organic synthesis is enormous, but is relatively underused. With the development of many highly effective chiral catalysts for imine additions, the situation will soon be changed. The present review will cover selected literature on catalytic asymmetric additions to aldimines, ketimines and related compounds including hydrazones, oximes and nitrones from 1999 to 2004. The reactions of interest include hydrogenation, alkylation, Mannich and related reactions such as aza-Baylis-Hillman and aza-Henry reaction, Strecker reaction, hydrophosphonylation, and 3-6 membered ring forming reactions from imines. Some applications of these methodologies in synthesis of nitrogen-containing biologically active compounds will also be presented.

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Short Enantioselective Total Syntheses of the Piperidine Alkaloids (S)-Coniine and (2R,6R)-trans-Solenopsin A via Catalytic Asymmetric Imine Hydrosilylation

Abstract: The enantioselective syntheses of (S)-coniine and (2R,6R)-trans-solenopsin A are reported. The key step in both syntheses is the catalytic asymmetric hydrosilylation of a cyclic imine.

Cited by 78 publications

References 38 publications

Hydrosilylation of Imines

Hydrosilylation of Imines

Intramolecular carbolithiation promoted by a DTBB-catalysed chlorine–lithium exchange

Recent Advances in Catalytic Asymmetric Addition to Imines and Related C=N Systems

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