A Theoretical and Experimental Study of the Asymmetric Addition of Dialkylzinc toN-(Diphenylphosphinoyl)benzalimine

Brandt, Peter; Hedberg, Christian; Lawonn, Klaus; Pinho, Pedro; Andersson, Pher G.

doi:10.1002/(sici)1521-3765(19990604)5:6<1692::aid-chem1692>3.0.co;2-m

Cited by 69 publications

(8 citation statements)

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“…Successful rationalizations of enantioselectivity depend on comprehensive knowledge about the reaction mechanism [17,18]. To verify the experimental results shown in Table 1, we embarked on a theoretical calculation of the deprotonation reaction of cyclohexene oxide using Gaussian 98.…”

Section: Theoretical Calculationssupporting

confidence: 66%

An experimental and theoretical study of the enantioselective deprotonation of cyclohexene oxide with isopinocampheyl-based chiral lithium amides

Xiao¹,

Jung²,

Gund³

et al.

Highlights in Computational Chemistry II

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The mechanism of the enantioselective deprotonation of cyclohexene oxide with isopinocampheyl-based chiral lithium amide was studied by quantum chemical calculations. The transition states of eight molecules were fully optimized at the ab initio HF/3-21G and density functional B3LYP/3-21G levels with Gaussian 98. The activation energies were calculated at the B3LYP/6-31+G (3df,2p)//B3LYP/3-21G level. We found the theoretical evaluation to be consistent with the experimental data. At the best case, an enantiomeric excess of up to 95% for (R)-2-scyclohexen-1-ol was achieved with (−)-N, N-diisopinocampheyl lithium amide.Keywords Theoretical study . Enantioselective deprotonation . Cyclohexene oxide . Chiral lithium amides . Density functional activation energy . B3LYP/6-31+G(3df,2p) Experimental dataLithium amides are an important class of reagents in organic synthesis and have been used extensively as strong bases for various reactions [1][2][3]. The deprotonation of an epoxide with a lithium amide to obtain an allylic alcohol was first reported in 1970 in a deuterium-labeling study by Thummel and Rickborn [4]. The reaction is thought to proceed via a cyclic six-membered transition state, formed by a 1:1 epoxide to base complex, where the base coordinates to the lone pair of electrons on oxygen, thereby facilitating the β-hydrogen removal. On the other hand, if a prochiral epoxide is deprotonated with a chiral lithium amide, it could give an optically active product. Such a rationale was first proposed over two decades ago, for a nonenzymatic "asymmetric deprotonation" of cyclohexene oxide to obtain 2-cyclohexen-1-ol (Scheme 1) [5].Over the years, a number of different chiral lithium amides have been designed and used for various deprotonation reactions [6]. As a result, asymmetric synthesis using chiral lithium amides has emerged as a useful method for the preparation of nonracemic compounds [7][8][9][10][11]. The methodology offers the advantage that the chiral auxiliaries can be recycled easily, thereby making the process effective and cost efficient. These chiral lithium bases have been exploited by a variety of efficient enantioselective reactions. Considering the remarkable success of pinene-based reagents for various organic transformations [12,13], we synthesized a set of chiral secondary amines derived from α-pinene (Scheme 2) (Malhotra and Brown 1998, unpublished results).The lithium salts of these amines were tested in the deprotonation of meso-epoxides [14]. Diisopinocampheylamine (DIPAM) prepared from (+)-α-pinene has the advantage of C 2 -symmetry. N-cyclohexyl-N-isopinocampheylamine (ChxIPAM), N-benzyl-N-isopinocampheylamine (BzIPAM) and N-isopropyl-N-isopinocampheylamine ( i PIPAM) were chosen to study the steric effect of the isopinocampheyl moiety in the deprotonation of a mesoepoxide to allylic alcohol. Reaction with a stoichiometric amount of DIPAM gave the product with >99% enantiomeric excess (EE) on deprotonation of cyclohexene oxide.To generate a catalytic cycle [15,16] (Scheme 3),...

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Section: Theoretical Calculationssupporting

confidence: 66%

An experimental and theoretical study of the enantioselective deprotonation of cyclohexene oxide with isopinocampheyl-based chiral lithium amides

Xiao¹,

Jung²,

Gund³

et al.

Highlights in Computational Chemistry II

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“…To this end, (3R)-3-amino-N-benzylpyrrolidine 16 was reacted with an enantiopure aldehyde 11 derived from bicyclic 2-azanorbornane. [10][11][12] Imine 17 was formed as a single stereoisomer in 89% yield (Scheme 5). This way, an enantiopure ligand was obtained combining two structural motifs -pyrrolidine and 2-azanorbornane.…”

Section: Scheme 4 Preparation Of Imine 15mentioning

confidence: 96%

“…[10][11][12] In our laboratory, it was utilized in the preparation of ligands bearing additional donor atoms (N, S, P, O) and polyamine derivatives exhibiting interesting antiproliferative activity. 10,13,14 In particular, amine 18 based on a 2-azanorbornyl skeleton was obtained from 11 via its conversion into an oxime followed by reduction.…”

Section: Scheme 5 Preparation Of Schiff Base 17mentioning

confidence: 99%

Chiral pyrrolidine thioethers and 2-azanorbornane derivatives bearing additional nitrogen functions. Enantiopure ligands for palladium-catalyzed Tsuji-Trost reaction

Wojaczyńska¹,

Kamińska²,

Wojaczyński³

et al. 2016

Arkivoc

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“…Aldehydes 4 and 5 were synthesized using the formerly described method. 10 Azide 12 was prepared as described previously. 16…”

confidence: 99%

Synthesis of terminal alkynes based on (1S,3R,4R)- and (1S,3S,4R)-2-azabicyclo[2.2.1]heptane

Wojaczyńska¹,

Steppeler²,

Górecki³

2020

Arkivoc

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A Theoretical and Experimental Study of the Asymmetric Addition of Dialkylzinc toN-(Diphenylphosphinoyl)benzalimine

Cited by 69 publications

References 0 publications

An experimental and theoretical study of the enantioselective deprotonation of cyclohexene oxide with isopinocampheyl-based chiral lithium amides

An experimental and theoretical study of the enantioselective deprotonation of cyclohexene oxide with isopinocampheyl-based chiral lithium amides

Chiral pyrrolidine thioethers and 2-azanorbornane derivatives bearing additional nitrogen functions. Enantiopure ligands for palladium-catalyzed Tsuji-Trost reaction

Synthesis of terminal alkynes based on (1S,3R,4R)- and (1S,3S,4R)-2-azabicyclo[2.2.1]heptane

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