The Coupling of Isonitriles and Carboxylic Acids Occurring By Sequential Concerted Rearrangement Mechanisms

Jones, Gavin O.; Li, Xuechen; Hayden, Amy E.; Houk, K. N.; Danishefsky, Samuel J.

doi:10.1021/ol8016287

Cited by 65 publications

(52 citation statements)

References 33 publications

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“…Isoimide 21 a rearranges to imide 10 a in an exothermic process via TS6 , which is the transition state for a concerted, pericyclic 1,3‐acyl shift, similar to that recently reported by Houk and Danishefsky et al . According to the data in Table , this rearrangement is both kinetically and thermodynamically more favourable in dichloromethane, compared with the gas phase, with the energies from the B3LYP computations being about 20 kJ mol −1 below those obtained with the M06‐2X density functional.…”

Section: Resultssupporting

confidence: 87%

“…Compared with the isoformimide, the structure of the isoacetimide is much closer to the ‘reactive’ geometry and does not require considerable structural or conformational changes, in particular the breaking of a hydrogen bond. We believe that similar conformational changes during the related isoformimide→formimide O–sp 2 N 1,3‐acyl rearrangement in Danishefsky's system provide a reasonable explanation for the required forcing conditions . With regards to this, it is worth noting that a stable ground‐state structure for the isoformimide 21 b with orthogonal ester and imine moieties (similar to the isoacetimide 21 a ) could not be located.…”

Section: Resultsmentioning

confidence: 94%

“…Whereas the isoformimide is planar [dihedral angle d (N‐C‐O‐C)=178°] as a result of hydrogen bonding between the imine proton and the carbonyl group, in isoacetimide 21 a the bulky ‘central’ methyl group twists the ester and imine moieties into an essentially perpendicular arrangement [ d (N‐C‐O‐C)≈101°]. This structural pre‐organisation in the isoacetimide is beneficial for the progression to TS6 for the pericyclic reaction, which requires an orthogonal orbital arrangement . Compared with the isoformimide, the structure of the isoacetimide is much closer to the ‘reactive’ geometry and does not require considerable structural or conformational changes, in particular the breaking of a hydrogen bond.…”

Section: Resultsmentioning

confidence: 99%

“…A recent computational study by Houk and Danishefsky et al. on the closely related isoformimide system (R 2 =H) revealed that the rearrangement C → D should, in fact, be considered as a concerted pseudopericyclic [1,3]‐acyl shift …”

Section: Introductionmentioning

confidence: 99%

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Synthesis of Peptides by Silver‐Promoted Coupling of Carboxylates and Thioamides: Mechanistic Insight from Computational Studies

Hutton

Shang

Wille

2016

Chemistry A European J

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The mechanism of the recently described N→C direction peptide synthesis through silver-promoted coupling of N-protected amino acids with thioacetylated amino esters was explored by using density functional theory. Calculation of the potential energy surfaces for various pathways revealed that the reaction proceeds through silver-assisted addition of the carboxylate to the thioamide, which is followed by deprotonation and silver-mediated extrusion of sulfur as Ag2 S. The resulting isoimide is the key intermediate, which subsequently rearranges to an imide through a concerted pericyclic [1,3]-acyl shift (O-sp(2) N 1,3-acyl migration). The proposed mechanism clearly emphasises the requirement of two equivalents of Ag(I) and basic reaction conditions, which is in full agreement with the experimental findings. Alternative rearrangement pathways involving only one equivalent of Ag(I) or through O-sp(3) N 1,3-acyl migration can be excluded. The computations further revealed that peptide couplings involving thioformamides require significant conformational changes in the intermediate isoformimide, which slow down the rearrangement process.

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Section: Resultssupporting

confidence: 87%

Section: Resultsmentioning

confidence: 94%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis of Peptides by Silver‐Promoted Coupling of Carboxylates and Thioamides: Mechanistic Insight from Computational Studies

Hutton

Shang

Wille

2016

Chemistry A European J

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“…The 2CC progression presumably commences via the reaction of an isonitrile ( 2 ) with a carboxylic acid ( 1 ), thereby generating a formimidate carboxylate mixed anhydride ( 3 ) 3. For ease of communication, we refer to such a structure as a “FCMA”.…”

mentioning

confidence: 99%

Thio FCMA Intermediates as Strong Acyl Donors: A General Solution to the Formation of Complex Amide Bonds

Rao

2009

J. Am. Chem. Soc.

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103

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Novel methodology for the formation of amide bonds under neutral conditions is described. Evidence is presented that the active acyl donors are thio FCMA intermediates, generated from the reactions of thioacids with isonitriles.Following explorations into the chemistry of isonitriles, 1 we were recently able to develop a new line of methodology which we consolidate in the expression, two-component coupling (2CC). 2 The 2CC progression presumably commences via the reaction of an isonitrile (2) with a carboxylic acid (1), thereby generating a formimidate carboxylate mixed anhydride (3). 3 For ease of communication, we refer to such a structure as a "FCMA". While no FCMA has been fully characterized, Rebek has brought to bear impressive evidence as to their existence 4 in special settings. It seems that under the usual reaction conditions, the oxy FCMA (3) is produced slowly and is disfavored at equilibrium. However, at higher temperatures under microwave mediation, the oxy FCMA, as its Z stereoisomer (3-Z), apparently undergoes a 1,3-O→N acyl transfer to generate an N-formylamide (4), 2b the end point of the 2CC reaction.In the short time since its discovery, the 2CC reaction has been adapted to the generation of a variety of biology related structures including secondary and tertiary amides and is already a valuable resource in the increasingly important field of chemoglycobiology. 5 In probing the matter further, it was discovered that the overall thio counterpart of the 2CC reaction, unlike the oxa version, occurs at room temperature. 2d,6 The throughput of thio FCMA (6) intermediates generated from reactions of 2 with thioacids (5), 7 is much greater than is the case for their oxy FCMA (3) counterparts. Moreover, the corresponding S→N rearrangement (see 6→7) is far more rapid than is its oxy counterpart (3→4 The value of the above described 2CC and thio 2CC chemistry was much enhanced as we learned how to synthesize, often for the first time, high value added isonitriles. 2f Application of the 2CC chemistry to merge "valuable" acids (as well as thioacids) with "valuable" isonitriles, provides access to useful peptide and glycopeptide substructural motifs. 2a-cEarlier we had considered the possibility of exploiting oxy FCMA intermediates (3) as potential bimolecular acylating agents (see 3 + NuH→8). 2d,e For such a prospectus to be feasible, bimolecular acylation had to dominate over monomolecular 1,3-O→N acyl transfer (leading to 4). In our initial reaction survey, conducted at room temperature, interdiction was, indeed, faster than 1,3 O→N intramolecular acyl transfer (i.e. 8 dominates over 4). However in the oxyacid experiments, the interdiction leading to 8 was quite slow and inefficient. 2b As the temperature was raised, the apparent rates of intramolecular 1,3-O→N acyl transfer become competitive with interdiction and a mixture of products ensued. Accordingly, attempts at efficient bimolecular acylation via oxy FCMA intermediates (3) were frustrated. Thus in our current modalities, the ultima...

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Molecular Rearrangements: Part 1. Pericyclic Molecular Rearrangements

Armstrong

Organic Reaction Mechanisms· 2005

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The Coupling of Isonitriles and Carboxylic Acids Occurring By Sequential Concerted Rearrangement Mechanisms

Cited by 65 publications

References 33 publications

Synthesis of Peptides by Silver‐Promoted Coupling of Carboxylates and Thioamides: Mechanistic Insight from Computational Studies

Synthesis of Peptides by Silver‐Promoted Coupling of Carboxylates and Thioamides: Mechanistic Insight from Computational Studies

Thio FCMA Intermediates as Strong Acyl Donors: A General Solution to the Formation of Complex Amide Bonds

Molecular Rearrangements: Part 1. Pericyclic Molecular Rearrangements

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