The Stabilizing Role of the Intramolecular C–H···O Hydrogen Bond in Cyclic Amides Derived From α-Methylbenzylamine

Sandoval‐Lira, Jacinto; Fuentes, Lilia; Quintero, Leticia; Höpfl, Herbert; Hernández-Pérez, Julio M.; Terán, Joel L.; Sartillo‐Piscil, Fernando

doi:10.1021/acs.joc.5b00286

Cited by 31 publications

(20 citation statements)

References 47 publications

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“…It is traditionally formulated as the positioning of two molecules such that the H atom of one molecule, A-H, acts as a bridge to an atom D of another molecule. Although its earliest conception considered only highly electronegative atoms like O, F, and N as donor and acceptors [1][2][3] , this picture has broadened considerably over recent years [4][5][6][7][8][9][10][11][12][13][14][15][16][17] . For example, despite some early resistance to the idea, the S atom is now recognized as a legitimate proton donor atom [18][19][20][21][22][23] .…”

Section: Introductionmentioning

confidence: 99%

Comparison of CH···O, SH···O, Chalcogen, and Tetrel Bonds Formed by Neutral and Cationic Sulfur-Containing Compounds

Scheiner

2015

J. Phys. Chem. A

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The ability of neutral and charged S-compounds to form different sorts of noncovalent bonds is examined by ab initio calculations. Neutrals are represented by CH3SH and fluoro-substituted FSCH3; cations are (CH3)3S(+), CH3SH2(+), and FHSCH3(+). Each is paired with N-methylacetamide (NMA) whose O atom serves as a common electron donor. Charged species engage in much stronger noncovalent bonds than do the neutral molecules, by as much as an order of magnitude. The strongest noncovalent bond for any system is a O···SF chalcogen bond wherein the O lies directly opposite a S-F covalent bond, amounting to as much as 39 kcal/mol. Second in binding energy is the SH···O H-bond, which can be as large as 34 kcal/mol. Somewhat weaker is the O···SC chalcogen bond, followed by the CH···O H-bond and finally the O···C tetrel bond, which has the appearance of a trifurcated H-bond. Any CH group that participates in a CH···O H-bond shifts its NMR signal downfield by an amount roughly proportional to the strength of the H-bond. This situation is clearly distinguishable from that in a O···S chalcogen or SH···O H-bond wherein the methyl protons are shifted upfield.

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Section: Introductionmentioning

confidence: 99%

Comparison of CH···O, SH···O, Chalcogen, and Tetrel Bonds Formed by Neutral and Cationic Sulfur-Containing Compounds

Scheiner

2015

J. Phys. Chem. A

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“…The importance of the C-HO interactions for the molecular conformation of amides has been previously established also by other research group. 34 The free energy of activation for the interconversion of compounds 3a-1 to 3a-4 has been investigated by means of dynamic NMR spectroscopy. 35,36 To measure the free energy of activation (ΔG  ) by variable temperature 1 H NMR spectroscopy, the coalescence temperature method can be used.…”

Section: Resultsmentioning

confidence: 99%

Synthesis and conformational analysis of novel tertiary amides derived from N-[(S)-α-phenylethyl]-1,3-imidazolidine

Santacruz-Jurez¹,

Hpfl²,

Huelgas³

et al. 2017

Arkivoc

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“…1), in which the preference for this isomer might arise from a favorable interaction between the ester carbonyl oxygen atom and the proton at the ring junction  to the nitrogen atom. 7 These are only 2.35 Å apart in compound 7b and this interaction could be present in the nitrone and in the transition state (see SI for DFT studies). To test the cycloaddition to give a cyclohexane ring system, we prepared the aldehyde 10 from the same ester 3 (Scheme 3).…”

Section: Scheme 1 Related Literature Example 4amentioning

confidence: 99%

Regiochemical and Stereochemical Studies of the Intramolecular Dipolar Cycloaddition of Nitrones Derived from Quaternary Aldehydes

Alkayar

Adams

Coldham

2015

Synlett

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Three aldehydes each with a quaternary  carbon stereocentre bearing an alkenyl, a phenyl, and a methyl ester group were treated with N-methylhydroxylamine. In each case bicyclic isoxazolidine products were formed by condensation to give intermediate nitrones that undergo intramolecular dipolar cycloaddition. The stereoselectivity was influenced by the -carbonyl substituent, possibly by a hydrogen bond between CO and a nearby CH of the nitrone in the transition state (supported by DFT and X-ray studies), and the regioselectivity was affected by the length of the tether and by the presence of an ester on the alkene dipolarophile.Key words: Cycloaddition; Diastereoselectivity; Domino reaction; Fused-ring systems; Heterocycles.Intramolecular dipolar cycloaddition reactions of nitrones have been known for more than 50 years. 1 One of the attractions of this chemistry is that it allows the rapid synthesis of cyclic and polycyclic compounds with 1,3-amino-alcohol functionality. The presence of polycyclic amines in alkaloids has prompted a considerable number of studies into intramolecular nitrone cycloadditions, 2 including work in our own research group. 3 Many alkaloids contain not just an amino group but an aromatic ring, often derived from a -arylethylamine precursor. Not surprisingly, therefore, there are reports of the intramolecular cycloadditions of nitrones bearing an aromatic substituent attached  to the nitrogen atom. 4,5 Of these examples, as far as we are aware, only one uses a quaternary aldehyde (compound 1) which was heated with N-methylhydroxylamine hydrochloride salt and pyridine to give the cycloadduct 2 as a single stereoisomer (Scheme 1). 4a We were interested in exploring further examples of this type of reaction of quaternary substituted aldehydes and report here our findings. Scheme 1 Related literature example. 4aIn related synthetic chemistry efforts, we wanted to test nitrone cycloadditions derived from aldehydes with an -quaternary stereocentre bearing an aryl group and an ester group. We therefore prepared the aldehyde 6 by double alkylation of the ester 3 followed by Swern oxidation 6 (Scheme 2). Scheme 2 Cycloaddition with aldehyde 6.Heating the aldehyde 6 with N-methylhydroxylamine hydrochloride salt and diisopropylethylamine in toluene gave a mixture of the cycloadducts 7a and 7b in a 1:1.6 ratio. The structures of both cycloadducts were determined by single crystal X-ray analysis (see Supporting Information, SI). This reaction is a direct comparison with the formation of the cycloadduct 2, where a single stereoisomer was reported. This suggests that, although a phenyl group has a stronger preference for the exo position than a methyl group, there is a preference for a methyl ester, rather than a phenyl group, to be exo. A possible reason for this is evident in the X-ray crystal structure of 7b (Fig. 1), in which the preference for this isomer might arise from a favorable interaction between the ester carbonyl oxygen atom and the proton at the ring junction  to the nitr...

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The Stabilizing Role of the Intramolecular C–H···O Hydrogen Bond in Cyclic Amides Derived From α-Methylbenzylamine

Cited by 31 publications

References 47 publications

Comparison of CH···O, SH···O, Chalcogen, and Tetrel Bonds Formed by Neutral and Cationic Sulfur-Containing Compounds

Comparison of CH···O, SH···O, Chalcogen, and Tetrel Bonds Formed by Neutral and Cationic Sulfur-Containing Compounds

Synthesis and conformational analysis of novel tertiary amides derived from N-[(S)-α-phenylethyl]-1,3-imidazolidine

Regiochemical and Stereochemical Studies of the Intramolecular Dipolar Cycloaddition of Nitrones Derived from Quaternary Aldehydes

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