Stabilities of stereoisomeric imine anions

Houk, K. N.; Strozier, Robert W.; Rondan, Nelson G.; Fraser, Robert R.; Chuaqui-Offermanns, Noemi

doi:10.1021/ja00524a039

Cited by 71 publications

(58 citation statements)

References 6 publications

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“…Degree of "Syn--Effect" for the g-Substituents of (E)--Vinylic Sulfones Several explanations for the "syn-effect" or related phenomena have been proposed, [19][20][21][22][23] namely: (1) 6p-electron homoaromaticity, 21 (2) s-orbital (s s* or n s*) interaction, 20,22 (3) dipole-dipole (electrostatic) interaction including lone pair-lone pair repulsion, 19,20,21d,23 (4) intramolecular hydrogen bonding, 20 and (5) chelation 19 (see Figure 6). In order to reveal which explanation is most reasonable in the case of the isomerization of vinylic sulfones to allylic sulfones, we tried to determine the relative degree of the "syn-effect" for the various g-substituents by a series of experiments for g-monosubstituted 24b, 25 and g,gdisubstituted 25 vinylic sulfones including the time-course of the reactions.…”

Section: Relativementioning

confidence: 99%

“…maticity seemed to be the most reasonable origin of the "syn-effect" among the several proposed explanations (Figures 6 and 7). [19][20][21][22][23] Namely, (1) 6p-electron homoaromaticity 21 was applicable to all of the g-substituents examined above except the cases such as i-propyl (30f), t-butyl (30g), and phenyl (30h) groups, which afforded (E)-allylic sulfones predominantly or exclusively (Table 3).…”

Section: Relativementioning

confidence: 99%

“…We proposed to call such an acidity of a proton characteristic to each conformation "conformational acidity" (a sort of kinetic acidity), 17 which essentially depends on a "syn-effect" [18][19][20][21][22][23] in the isomerization of vinylic sulfones. It should be noted that though the anionic intermediate 24 is thermodynamically more stable than its (Z)-isomer 21 as described above, such a result could not be observed in the Ramberg-Bäcklund reactions, since the desulfonylation from 21 to 22 (or from 24 to 25) took place soon after the isomerization via 20 (or 23) at low temperature.…”

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"Syn-Effect" in the Base-Induced Isomerization of Vinylic Sulfones to Allylic Sulfones and the Related Various Reactions

Inomata

2009

J. Synth. Org. Chem. Jpn.

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: "Syn-effect" has been recognized as a major cause of stabilizing the syn-conformation at the transition state of a number of reactions against the steric hindrance. This account deals with the origin of the "syn-effect" on the basis of the stereochemical outcome in the isomerization of vinylic sulfones leading to the formation of allylic sulfones and in the related various reactions. We proposed that a s p* interaction between the s-orbital(s) of the allylic C-H s-bond(s) (or of the C-H s-bond(s) at the a-position for carbonyl compounds) and the antibonding orbital (p*) of the C=C double bond (or of the C=O double bond for carbonyl compounds) is the most important and essential factor for the "syn-effect", though the contribution of a 6p-electron homoaromaticity and/or of a hydrogen bonding cannot be entirely ruled out. Scheme 2fied (Scheme 3). 13Therefore, we started to prepare stereochemically well-defined vinylic sulfones and study the detailed stereochemistry of the isomerization. Consequently, we have found that (E)-vinylic sulfones preferentially provided sterically unfavorable (Z)-allylic sulfones, whose stereochemical course was explainable by so-called "syn-effect". Herein we will briefly introduce the stereochemical outcome in the isomerization of vinylic sulfones to allylic sulfones and in the related various reactions, and discuss the origin of this effect in detail. Regio--and Stereoselective Preparation of Vinylic SulfonesOur initial study focused on the stereoselective synthesis of (E)-and (Z)-vinylic sulfones 14, since the iodotosylation of 1-alkenes followed by triethylamine-induced dehydroiodination of the resulting 2-iodo-1-tosylalkanes 13 mostly provided a mixture of (E)-and (Z)-isomers of vinylic sulfones 14 as summarized in Scheme 4 and their separation into pure isomers turned out to be difficult. [14][15][16] Gratifyingly, 2-pyrrolidinyl-1-tosylalkanes 15 derived from 13 and an excess amount of pyrrolidine underwent a selective Cope elimination upon treatment of the crude products 15 with mCPBA in dichloromethane in the presence of Na 2 CO 3 to provide stereochemically pure (E)-vinylic sulfones (E)-14 in high yields (Scheme 5). 17 This procedure was much easier than an alternative method via a-phenylselenation of 1-tosylalkanes 16 and was applicable on a large scale.A possible key factor for success in the exclusive formation of (E)-14 may be the formation of 16 in favor of 17 in the transition state where the N-oxy-1-pyrrolidinyl group and the hydrogen should adopt eclipsed conformation, in order to avoid a severe steric congestion developed by an alkyl substituent R and the tosyl group (Ts) in 17 (Figure 2).The intermediary b-pyrrolidinylsulfones 15 were also used to prepare a-alkylated vinylic sulfones through a-alkylation followed by oxidative elimination of the pyrrolidinyl group. 15On the other hand, (Z)-14 were selectively synthesized in high yields by the Pd-catalyzed hydrogenation of (E)-2-iodo-1-tosyl-1-alkenes 18, which were prepared by the regio-and stereoselectiv...

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Section: Relativementioning

confidence: 99%

Section: Relativementioning

confidence: 99%

mentioning

confidence: 99%

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"Syn-Effect" in the Base-Induced Isomerization of Vinylic Sulfones to Allylic Sulfones and the Related Various Reactions

Inomata

2009

J. Synth. Org. Chem. Jpn.

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“…13 Thus, we presumed that the enantioselectivity in eq 1 derives from a well-defined chiral aggregate, 2 , composed of the dilithium enediolate and the chiral dilithium amide. 11,14 The optimized conditions suggested a 1:1 stoichiometry, although that assertion lacked direct support.…”

Section: Introductionmentioning

confidence: 99%

Enediolate–Dilithium Amide Mixed Aggregates in the Enantioselective Alkylation of Arylacetic Acids: Structural Studies and a Stereochemical Model

Stivala

Wright

et al. 2013

J. Am. Chem. Soc.

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A combination of X-ray crystallography, 6Li, 15N, and 13C NMR spectroscopies, and density functional theory computations afford insight into the structures and reactivities of intervening aggregates underlying highly selective asymmetric alkylations of carboxylic acid dianions (enediolates) mediated by the dilithium salt of a C2-symmetric chiral tetraamine. Crystallography shows a trilithiated n-butyllithium-dilithiated amide that has dimerized to a hexalithiated form. Spectroscopic studies implicate the non-dimerized trilithiated mixed aggregate. Reaction of the dilithiated amide with phenylacetic acid with excess n-butyllithium affords a tetralithio aggregate comprised of the two dianions in solution and the dimerized octalithio form in the solid state. Computational studies shed light on the details of the solution structures and afford a highly predictive stereochemical model.

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“…Obviously, the syn orientation of the carbanionic center and the N-alkyl substituent in the lithiated Schiff base is more favorable from the viewpoint of thermodynamics, and C-alkylation of the lithium derivative is kinetically preferred. The syn configuration of lithiated and alkylated imines was confirmed by ab initio calculations [7], NMR data [8], and studies on the stereochemistry of α-alkylation of various lithiated Schiff bases [9][10][11]. For example, Frazer et al [8] performed 13 C NMR monitoring of α-alkylation of metalated Schiff bases derived from cycloalkanones and detected only unstable syn-alkylated species, while Smith et al [9] observed formation (96%) of a very unstable synalkylated Schiff base in the methylation of a metalated butyraldehyde imine derivative.…”

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confidence: 79%

A Simple Diastereoselective Synthesis of Chiral Nonracemic Aliphatic Amines

2005

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An efficient procedure has been developed for the diastereoselective synthesis of chiral aliphatic amines (diastereoisomeric excess >96%) from (1S)-N-(1-methylethylidene)-1-phenylethylamine, i.e., Schiff base derived from the simplest ketone (acetone) and (1S)-1-phenylethylamine. The procedure includes successive lithiation, alkylation, and reduction and is characterized by high regioselectivity in the formation of alkylated syn-Z-imines. Hydride reduction of the prochiral C=N bond in the latter gives mainly optically active aliphatic amines with R configuration. All reactions are performed as a one-pot process without isolation of intermediate products.RHlg = MeI (a), EtI (b), CH 2 =CHCH 2 Br (c), 4-MeC 6 H 4 CH 2 I (d).Enantiomerically pure amines are widely used as chiral auxiliaries for resolution of racemic mixtures in asymmetric synthesis, chiral ligands in metal-complex catalysis, and chiral building blocks in the preparation of synthetic and natural biologically active compounds [1][2][3][4][5].In the present communication we describe an efficient stereoselective synthesis of chiral aliphatic amines having R configuration from (1S)-N-(1-methylethylidene)-1-phenylethylamine (I) which is obtained from the simplest ketone, acetone, and (1S)-1-phenylethylamine. The proposed procedure ensures more than 96% diastereoisomeric excess. Metalation of Schiff base I with lithium diethylamide in THF at -20°C, followed by alkylation with methyl iodide at -80°C and reduction with 4 equiv of sodium tetrahydridoborate at -80°C in the presence of 40 equiv of isopropyl alcohol, gave a mixture of (R C ,S N )-and (S C ,S N )-epimeric amines IIIa and IVa (the former prevailing, de 79%) through intermediate syn- Z-imine

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Stabilities of stereoisomeric imine anions

Cited by 71 publications

References 6 publications

"Syn-Effect" in the Base-Induced Isomerization of Vinylic Sulfones to Allylic Sulfones and the Related Various Reactions

"Syn-Effect" in the Base-Induced Isomerization of Vinylic Sulfones to Allylic Sulfones and the Related Various Reactions

Enediolate–Dilithium Amide Mixed Aggregates in the Enantioselective Alkylation of Arylacetic Acids: Structural Studies and a Stereochemical Model

A Simple Diastereoselective Synthesis of Chiral Nonracemic Aliphatic Amines

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