<i>gem</i>-Disubstituent Effect:  Theoretical Basis and Synthetic Applications

Jung, Michael E.; Piizzi, Grazia

doi:10.1021/cr940337h

Cited by 825 publications

(668 citation statements)

References 150 publications

(201 reference statements)

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“…3, 51 As noted above, the parent aminopentene is not efficiently cyclized by any of these chiral oxazolinylborate catalysts. Accordingly, the rate of cyclization of 2-phenylpent-4-en-1-amine 22a is decreased significantly compare to the diphenylaminopentene 8a.…”

Section: Journal Of the American Chemical Societymentioning

confidence: 95%

Highly Enantioselective Zirconium-Catalyzed Cyclization of Aminoalkenes

et al. 2013

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Aminoalkenes are catalytically cyclized in the presence of cyclopentadienylbis(oxazolinyl)borato group 4 complexes {PhB(C5H4)(OxR)2}M(NMe2)2 (M = Ti, Zr, Hf; OxR = 4,4-dimethyl-2-oxazoline, 4S-isopropyl-5,5-dimethyl-2-oxazoline, 4S-tert-butyl-2-oxazoline) at room temperature and below, affording five-, six-, and seven-membered N-heterocyclic amines with enantiomeric excesses of >90% in many cases and up to 99%. Mechanistic investigations of this highly selective system employed synthetic tests, kinetics, and stereochemistry. Secondary aminopentene cyclizations require a primary amine (1-2 equiv vs catalyst). Aminoalkenes are unchanged in the presence of a zirconium monoamido complex {PhB(C5H4)(Ox4S-iPr,Me2)2}Zr(NMe2)Cl or a cyclopentadienylmono(oxazolinyl)borato zirconium diamide {Ph2B(C5H4)(Ox4S-iPr,Me2)}Zr(NMe2)2. Plots of initial rate versus [substrate] show a rate dependence that evolves from first-order at low concentration to zero-order at high concentration, and this is consistent with a reversible substrate-catalyst interaction preceding an irreversible step. Primary kinetic isotope effects from substrate conversion measurements (k′obs(H)/k′obs(D) = 3.3 ± 0.3) and from initial rate analysis (k2(H)/k2(D) = 2.3 ± 0.4) indicate that a N-H bond is broken in the turnover-limiting and irreversible step of the catalytic cycle. Asymmetric hydroamination/cyclization of N-deutero-aminoalkenes provides products with higher optical purities than obtained with N-proteo-aminoalkenes. Transition state theory, applied to the rate constant k2 that characterizes the irreversible step, provides activation parameters consistent with a highly organized transition state (ΔS⧧ = −43(7) cal·mol-1 K-1) and a remarkably low enthalpic barrier (ΔH⧧ = 6.7(2) kcal·mol-1). A six-centered, concerted transition state for C-N and C-H bond formation and N-H bond cleavage involving two amidoalkene ligands is proposed as most consistent with the current data. ABSTRACT: Aminoalkenes are catalytically cyclized in the presence of cyclopentadienylbis(oxazolinyl)borato group 4 complexes {PhB(C 5 H 4 )(Ox R ) 2 }M(NMe 2 ) 2 (M = Ti, Zr, Hf; Ox R = 4,4-dimethyl-2-oxazoline, 4S-isopropyl-5,5-dimethyl-2-oxazoline, 4S-tert-butyl-2-oxazoline) at room temperature and below, affording five-, six-, and seven-membered N-heterocyclic amines with enantiomeric excesses of >90% in many cases and up to 99%. Mechanistic investigations of this highly selective system employed synthetic tests, kinetics, and stereochemistry. Secondary aminopentene cyclizations require a primary amine (1−2 equiv vs catalyst). Aminoalkenes are unchanged in the presence of a zirconium monoamido complex {PhB(C 5 H 4 )(Ox 4S-iPr,Me 2 ) 2 }Zr(NMe 2 )Cl or a cyclopentadienylmono(oxazolinyl)borato zirconium diamide {Ph 2 B(C 5 H 4 )-(Ox 4S-iPr,Me 2 )}Zr(NMe 2 ) 2 . Plots of initial rate versus [substrate] show a rate dependence that evolves from first-order at low concentration to zero-order at high concentration, and this is consistent with a reversible substrate−catalyst interac...

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Section: Journal Of the American Chemical Societymentioning

confidence: 95%

Highly Enantioselective Zirconium-Catalyzed Cyclization of Aminoalkenes

et al. 2013

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“…24 It has been hypothesized that this effect arises from conforma-tionally destabilized ground states of gem-dimethyl substituted substrates compared to those lacking substitution. 25 Similarly, the efficiency of certain enzyme-catalyzed cyclizations has been attributed in part to conformational control of the bound substrate by the enzyme active site.…”

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confidence: 99%

Selective Monoterpene-like Cyclization Reactions Achieved by Water Exclusion from Reactive Intermediates in a Supramolecular Catalyst

et al. 2012

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A polyanionic supramolecular assembly (1) is shown to catalytically cyclize the monoterpene citronellal and two homologues. In contrast to cyclization in acidic aqueous solution, the hydrophobic interior of 1 prevents the capture of reactive intermediates by water. This effect was also observed in the gold-catalyzed cycloisomerization of an enyne. Due to the steric confinement of the catalyst's interior, Prins cyclizations in 1 proceed cleanly both for substrates containing and lacking gem-dimethyl substitution. Encapsulation in 1 consequently imposes a degree of mechanistic control that, similar to enzyme catalysis, is not observed in bulk aqueous solution.

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“…Cyclopropyl tethered methylenecyclopropanes can give the expected PK products or rearranged hydroindenones in which neither of the two carbon atoms of the alkyne form part of the cyclopentenone ring in the final product [42]. Other substrates like enamines (23) and ynamines (24) undergo readily this reaction (Fig. 2) [44][45][46][47].…”

Section: Methodsmentioning

confidence: 99%

“…The first intramolecular PKR was reported by Schore and allows the formation of 5,5-and 5,6-fused bicycles, and more recently even some 5,7-bicycles. In general, good conversions are achieved only with gem-disubstituted enynes (Scheme 3) [22][23][24].…”

Section: Scope and Limitationsmentioning

confidence: 99%