New, General, and Practical Enamine Cyclopropanation Using Dichloromethane

Tsai, Chia-Chung; Hsieh, I-Lin; Cheng, Tsung‐Ting; Tsai, Ping-Kuei; Lin, Kuo‐Wei; Yan, Tong

doi:10.1021/ol0604365

Cited by 38 publications

(21 citation statements)

References 27 publications

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“…At the outset of this study, however, it was not clear how the nitrogen of the enamine would impact the reactivity of the double bond toward cyclopropanation or if it would affect the diastereoselectivity. A search of the literature revealed very few examples of Simmons-Smith cyclopropanations of enamines 50,103. Nonetheless, we attempted the tandem asymmetric amino vinylation/diastereoselective cyclopropanation.…”

Section: Resultsmentioning

confidence: 99%

Stereoselective Synthesis of β-Hydroxy Enamines, Aminocyclopropanes, and 1,3-Amino Alcohols via Asymmetric Catalysis

2010

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Tandem methods for the catalytic asymmetric preparation of enantioenriched β-hydroxy (E)-enamines and cyclopropylamines are presented. The diastereoselective hydrogenation of enantioenriched (E)-trisubstituted hydroxy enamines to generate 1,2-disubstituted 1,3-amino alcohols is also outlined. These methods are initiated by highly regioselective hydroboration of N-tosyl substituted ynamides with diethylborane to generate β-amino alkenyl boranes. In situ boron to zinc transmetalation generates β-amino alkenyl zinc reagents. These functionalized vinylzinc intermediates were subsequently added to aldehydes in the presence of catalyst derived from an enantioenriched amino alcohol (morpholino isoborneol, MIB). The catalyst promotes highly enantioselective C–C bond-formation to provide β-hydroxy enamines in good isolated yields (68–86%) with 54–98% enantioselectivity. The intermediate zinc β-alkoxy enamines can be subjected to a tandem cyclopropanation to afford amino cyclopropyl carbinols with three continuous stereocenters in a one-pot procedure with good yields (72–82%), enantioselectivities of 76–94% and diastereomeric ratios >20:1. Diastereoselective hydrogenation of isolated enantioenriched β-hydroxy enamines over Pd/C furnished syn-1,2-disubstituted-1,3-amino alcohols with high yields (82–90%) and moderate to excellent diastereoselectivities. These methods were used in an efficient preparation of the enantioenriched precursor to PRC200-SS derivatives, which are potent serotonin-norepinephrine-dopamine reuptake inhibitors.

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Section: Resultsmentioning

confidence: 99%

Stereoselective Synthesis of β-Hydroxy Enamines, Aminocyclopropanes, and 1,3-Amino Alcohols via Asymmetric Catalysis

2010

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“…Very often, alkenes serve as starting materials and are cyclopropanated according to a broad variety of well-established protocols. In addition to these, esters 333 and N,N-dialkylcarboxamides, 334,335 nitriles, 334a,b ketocarbonyl groups, 336 and eneamines 337 can be converted into variously substituted cyclopropanes. Depending on the functionalities present in the precursor, the appropriate protocol for the cyclopropanations must be chosen.…”

Section: Oligocyclopropyl-substituted Alkanes Alkenes and Alkynesmentioning

confidence: 99%

Three-Membered-Ring-Based Molecular Architectures

2006

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“…The activation of a C–Cl bond in chloroalkanes under mild conditions represents a considerable challenge of academic interest, as the resulting products constitute a potentially useful source of alkylating agents . Although oxidative addition of CH 3 X (X = I, Br, Cl), CH 2 I 2 , CH 2 ClI, and CH 2 Br 2 to various transition metal centers is well documented in the literature (used in, for example, Simmons–Smith cyclopropanation), activation of the relatively inert C–Cl bond, especially of the cheap CH 2 Cl 2 reagent, is more challenging than that of C–Br or C–I bonds .…”

Section: Introductionmentioning

confidence: 99%

Facile and Room-Temperature Activation of C_sp3–Cl Bonds by Cheap and Air-Stable Nickel(II) Complexes of (N-Thioether) DPPA-Type Ligands

et al. 2014

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Reaction of the diphosphine (P,P) ligand N(PPh2)2(n-PrSMe) (1) or N(PPh2)2(p-(SMe)C6H4) (2) with [Ni(NCMe)6][BF4]2 in a 2:1 molar ratio afforded the bis-chelated, dicationic Ni(II) complexes [Ni(1)2][BF4]2 (3) and [Ni(2)2][BF4]2 (4), respectively. Both complexes were characterized in solution by various spectroscopic techniques and in the solid state by X-ray diffraction studies. In the presence of Zn metal used as cheap reductant, complexes 3 and 4 activate the inert C–Cl bonds of dichloromethane at room temperature to afford in high yield the phosphonium ylide derivatives [Ni((Ph2P)N{P(CH2)Ph2}(n-PrSMe)-P,C)2][BF4]2 (5) and [Ni((Ph2P)N{P(CH2)Ph2}(p-(SMe)C6H4)-P,C)2][BF4]2 (6), respectively. The formation of [Ni((Ph2P)N{P(CH2)Ph2}(n-PrSMe)-P,C)2]Cl2 (5′), an analogue of complex 5, from a Ni(0) precursor supports the reduction of the Ni(II) precursors by the Zn reagent prior to C–Cl bond activation. The structures of 5 and 5′ were unambiguously established by X-ray diffraction analysis.

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New, General, and Practical Enamine Cyclopropanation Using Dichloromethane

Cited by 38 publications

References 27 publications

Stereoselective Synthesis of β-Hydroxy Enamines, Aminocyclopropanes, and 1,3-Amino Alcohols via Asymmetric Catalysis

Stereoselective Synthesis of β-Hydroxy Enamines, Aminocyclopropanes, and 1,3-Amino Alcohols via Asymmetric Catalysis

Three-Membered-Ring-Based Molecular Architectures

Facile and Room-Temperature Activation of C_sp3–Cl Bonds by Cheap and Air-Stable Nickel(II) Complexes of (N-Thioether) DPPA-Type Ligands

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New, General, and Practical Enamine Cyclopropanation Using Dichloromethane

Cited by 38 publications

References 27 publications

Stereoselective Synthesis of β-Hydroxy Enamines, Aminocyclopropanes, and 1,3-Amino Alcohols via Asymmetric Catalysis

Stereoselective Synthesis of β-Hydroxy Enamines, Aminocyclopropanes, and 1,3-Amino Alcohols via Asymmetric Catalysis

Three-Membered-Ring-Based Molecular Architectures

Facile and Room-Temperature Activation of Csp3–Cl Bonds by Cheap and Air-Stable Nickel(II) Complexes of (N-Thioether) DPPA-Type Ligands

Contact Info

Product

Resources

About

Facile and Room-Temperature Activation of C_sp3–Cl Bonds by Cheap and Air-Stable Nickel(II) Complexes of (N-Thioether) DPPA-Type Ligands