Using Hydrogen Bonding to Control Carbamate C−N Rotamer Equilibria

Moraczewski, Alexei L.; Banaszynski, Laura A.; From, Aaron M.; White, Courtney; Smith, Bradley D.

doi:10.1021/jo980644d

Cited by 64 publications

(54 citation statements)

References 17 publications

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“… 28 The anti rotamer is usually favored by 1.0–1.5 kcal mol –1 for steric and electrostatic reasons with respect to the syn counterpart. 22 In many cases, the energy difference may be close to zero. As a result, those carbamates are found as an approximately 50:50 mixture of syn and anti isomers, as in the case of a number of Boc-protected amino acid derivatives.…”

Section: Organic Carbamates: Applications and Chemical And Metabolic mentioning

confidence: 99%

“…Intra- and intermolecular hydrogen bonding may also perturb the syn – anti isomer equilibrium of carbamates. 22 , 25 , 30 …”

Section: Organic Carbamates: Applications and Chemical And Metabolic mentioning

confidence: 99%

“… 22 The authors examined the abilities of acetic acid and 2,6-bis(octylamido)pyridine ( 3 ) to perturb the syn / anti ratio of carbamates 1 and 2 (Figure 4 ). 22 …”

Section: Organic Carbamates: Applications and Chemical And Metabolic mentioning

confidence: 99%

See 2 more Smart Citations

Organic Carbamates in Drug Design and Medicinal Chemistry

2015

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The carbamate group is a key structural motif in many approved drugs and prodrugs. There is an increasing use of carbamates in medicinal chemistry and many carbamate derivatives are specifically designed to make drug-target interactions through their carbamate moiety. In this review, we present properties and stabilities of carbamates, reagents and chemical methodologies for the synthesis of carbamates, and recent application of carbamates in drug design and medicinal chemistry.

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Section: Organic Carbamates: Applications and Chemical And Metabolic mentioning

confidence: 99%

“…Intra- and intermolecular hydrogen bonding may also perturb the syn – anti isomer equilibrium of carbamates. 22 , 25 , 30 …”

Section: Organic Carbamates: Applications and Chemical And Metabolic mentioning

confidence: 99%

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Organic Carbamates in Drug Design and Medicinal Chemistry

2015

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“…This feature raises their potential as a structural module for noncovalent synthesis 92. Numerous structural variations of readily available heteroaromatics, such as pyridine93–96 and triazine,95, 97 have been studied in great detail. Since homodimerization is intrinsically not possible for 3‐H‐bond motifs, these complexes have often been designed as receptors 98, 99.…”

Section: Self‐assembly By H‐bond‐directed Dimerizationmentioning

confidence: 99%

Noncovalent Synthesis Using Hydrogen Bonding

Prins

Reinhoudt

Timmerman

2001

Angew. Chem. Int. Ed.

1,249

765

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Hydrogen bonds are like human beings in the sense that they exhibit typical grouplike behavior. As an individual they are feeble, easy to break, and sometimes hard to detect. However, when acting together they become much stronger and lean on each other. This phenomenon, which in scientific terms is called cooperativity, is based on the fact that “1+1 is more than 2”. By using this principle, chemists have developed a wide variety of chemically stable structures that are based on the reversible formation of multiple hydrogen bonds. More than 20 years of fundamental studies on these phenomena have gradually developed into a new discipline within the field of organic synthesis, and is nowadays called “noncovalent synthesis”. This review describes noncovalent synthesis based on the reversible formation of multiple hydrogen bonds. Starting with a thorough description of what the “hydrogen bond” really is, it guides the reader through a variety of bimolecular and higher order assemblies and exemplifies the general principles that determine their stability. Special focus is given to reversible capsules based on hydrogen‐bonding interactions that exhibit interesting encapsulation phenomena. Furthermore, the role of hydrogen‐bond formation in self‐replicating processes is actively discussed, and finally the review briefly summarizes the development of novel materials (nanotubes, liquid crystals, polymers, etc.) and principles (dynamic libraries) that recently have emanated from this intriguing field of research.

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“…[46] As was to be expected in the case of such compounds, the 1 H NMR spectra of each pair of diastereomers presented a rather poor resolution in several solvents, [47] in particular around the methoxy chemical shift area. This observation is mainly due to the existence of two conformers (a well-known phenomenon, especially in the case of five-membered rings), [48,49] which arise from the strong steric hindrance between the Boc (or Cbz) and the oxazolidine dimethyl groups. Indeed, a fast rotation of the carbamate is hardly possible and thus engenders the existence of two distinct rotamers.…”

Section: Resultsmentioning

confidence: 99%