Stereoconservative reductive methyl- and dimethylamination of isomeric 3,3-diarylpropenals. Synthetic and mechanistic studies on control of the stereochemistry

Hoegberg, Thomas; Ulff, Bengt

doi:10.1021/jo00196a021

Cited by 15 publications

(9 citation statements)

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“…The reported non‐stereoselective method13 for the synthesis of 3 involved the following reaction sequence: 1) addition of allylmagnesium chloride with p ‐bromophenyl 3‐pyridyl ketone, giving the tertiary allyl alcohol; 2) successive acid‐promoted allyl rearrangement, giving the allyl chloride; and 3) final dimethylamination. On the other hand, stereoselective synthesis14 was performed proficiently by a rigorous pH‐controlled reductive amination procedure. Due to the difficulty of stereocontrol, and oxidation as a side reaction, reductive amination steps were required.…”

Section: Resultsmentioning

confidence: 99%

“…5) Overall yields were 33 % for ( Z )‐ 3 and 45 % for ( E )‐ 3 after each five parallel steps. Compared with extensive studies on the synthesis for ( E )‐ and ( Z )‐ 3 ,13, 14 which involved MnO 2 oxidation of allylic alcohol followed by reductive amination or dimethylamination, the present method is of highly concise and orthogonal without tedious pH‐dependent separation.…”

Section: Resultsmentioning

confidence: 99%

“…( Z )‐3‐(4‐Bromophenyl)‐3‐(3‐pyridinyl)prop‐2‐en‐1‐ol 14 (Scheme , [i]‐(i)) : DIBAL (42.4 mL; 1.0 M in toluene) was added to a stirred solution of the ester ( Z )‐ 11 (3.36 g, 10.6 mmol) in THF (21.2 mL) at −78 °C under an argon atmosphere, and the mixture was stirred at the same temperature for 0.5 h. MeOH (ca. 30 mL) and a saturated aqueous solution of Na/K tartrate (ca.…”

Section: Methodsmentioning

confidence: 99%

“…Compound ( Z )‐3 14 (Scheme , [i]‐(ii)) : SOCl 2 (0.10 mL, 1.35 mmol) and DMF (1 drop) were successively added to a stirred solution of the allyl alcohol (261 mg, 0.900 mmol) in CH 2 Cl 2 (0.9 mL) at 20–25 °C, and the mixture was stirred at the same temperature for 10 min. Then, an aqueous solution of Me 2 NH (0.95 mL, 9.5 M ) was added to the mixture followed by stirring for 0.5 h. A saturated aqueous solution of NaHCO 3 was added to the mixture, which was extracted three times with AcOEt.…”

Section: Methodsmentioning

confidence: 99%

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(E)‐,(Z)‐Parallel Preparative Methods for Stereodefined β,β‐Diaryl‐ and α,β‐Diaryl‐α,β‐unsaturated Esters: Application to the Stereocomplementary Concise Synthesis of Zimelidine

Ashida

Sato

Suzuki

et al. 2015

Chemistry A European J

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Parallel and practical methods for the preparation of both (E)- and (Z)-β-aryl(1)-β-aryl(2)-α,β-unsaturated esters 1 and (E)- and (Z)-α-aryl(1)-β-aryl(2)-α,β-unsaturated esters 2 are described. These methods involve accessible, robust, stereocomplementary N-methylimidazole (NMI)-mediated enol tosylations (14 examples, 70-99% yield), as well as stereoretentive Suzuki-Miyaura cross-couplings (36 examples, 64-99% yield). The highlighted feature of the present protocol is the use of parallel and stereocomplementary approaches to obtain highly (E)- and (Z)-pure products 1 and 2 by utilizing sequential enol tosylations and cross-coupling reactions. An expeditious and parallel synthesis of (E)- and (Z)-zimelidine (3), which is a highly representative selective serotonin reuptake inhibitor (SSRI), was performed by utilizing the present methods.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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(E)‐,(Z)‐Parallel Preparative Methods for Stereodefined β,β‐Diaryl‐ and α,β‐Diaryl‐α,β‐unsaturated Esters: Application to the Stereocomplementary Concise Synthesis of Zimelidine

Ashida

Sato

Suzuki

et al. 2015

Chemistry A European J

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“…To the best of our knowledge, there have been no reports of carbonylative Suzuki coupling from isocyanides to generate biaryl ketones. In a model experiment, phenylboronic acid and iodobenzene were reacted with tert-butyl isocyanide in Pd(OAc) 2 and Ph 3 P with K 2 CO 3 as base. The reaction was firstly performed in dry toluene at 110 °C for four hours, then it was hydrolyzed in HCl-THF, and the desired product benzophenone was formed in 71% yield (Table 1, entry 1).…”

mentioning

confidence: 99%

Palladium-Catalyzed Synthesis of Biaryl Ketones via tert-Butyl Isocyanide Insertion

Chen¹,

Duan²,

Xiao³

et al. 2014

Synlett

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A simple and efficient palladium-catalyzed carbonylative Suzuki coupling via tert-butyl isocyanide insertion has been developed, which demonstrates the utility of isocyanides in intermolecular C-C bond construction. This methodology provides a novel pathway for the synthesis of diaryl ketones in moderate to good yields. The approach is tolerant to a wide range of substrates and applicable to library synthesis. A possible reaction mechanism was proposed based on the experimental results.

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Reductive Aminations of Carbonyl Compounds with Borohydride and Borane Reducing Agents

2002

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Reductive amination is an important tool for synthetic organic chemists in the construction of carbon‐nitrogen bonds. This reaction, also termed reductive alkylation, involves condensation of an aldehyde or ketone with an amine in the presence of a reducing agent. A wide variety of substrates can be used including aliphatic and aromatic aldehydes and ketones, and even benzophenones. A range of amines from ammonia to aromatic amines, including those with electron‐withdrawing substituents, can be employed. For particularly sluggish reactions, such as those involving weakly electrophilic carbonyl groups, poorly nucleophilic amines, or sterically congested reactive centers, additives such as molecular sieves or Lewis acids are often useful. This chapter focuses on those conditions in which the carbonyl component, amine, and reducing reagent react in the same vessel. This review is restricted to reductive aminations using borohydride and borane reducing agents. This chapter concentrates on reductive amination chemistry mediated by borohydride and other boron‐containing reducing agents from 1971, the year when sodium cyanoborohydride was introduced, through the middle of 1999. In addition to reductive aminations of aldehyde and ketone substrates, reactions of related structures including acetals, aminals, ketals, carboxylic acids, nitriles, and dicarbonyls that form a nitrogen‐containing ring are reviewed. Intramolecular processes in which the substrate contains both the carbonyl and amine moieties are described. The intramolecular variant is a useful method for preparing cyclic amines. All of the various boron‐containing hydride sources in reductive aminations, including labeled metal hydrides, are reviewed. Instances of reductive aminations that failed are described. Applications of this method to a solid support in parallel synthesis in combinatorial chemistry as well as reductive aminations that proceed in tandem with a second reaction such as reductive lactamizations are discussed.

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Stereoconservative reductive methyl- and dimethylamination of isomeric 3,3-diarylpropenals. Synthetic and mechanistic studies on control of the stereochemistry

Cited by 15 publications

References 0 publications

(E)‐,(Z)‐Parallel Preparative Methods for Stereodefined β,β‐Diaryl‐ and α,β‐Diaryl‐α,β‐unsaturated Esters: Application to the Stereocomplementary Concise Synthesis of Zimelidine

(E)‐,(Z)‐Parallel Preparative Methods for Stereodefined β,β‐Diaryl‐ and α,β‐Diaryl‐α,β‐unsaturated Esters: Application to the Stereocomplementary Concise Synthesis of Zimelidine

Palladium-Catalyzed Synthesis of Biaryl Ketones via tert-Butyl Isocyanide Insertion

Reductive Aminations of Carbonyl Compounds with Borohydride and Borane Reducing Agents

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