The 1-Norbornene Skeleton by Carbene Rearrangement

Abstract

Faustregeln: Die Entscheidung über das Schicksal eines Wirkstoffkandidaten nach grober Abschätzung seiner oralen Bioverfügbarkeit hängt von der Aussagekraft der Selektionsparameter ab. Eine retrospektive Analyse ergab, dass Lipophilie, Anteil an polarer Oberfläche und Zahl der H‐Brückendonoren marktgängiger Arzneimittel über die Jahre relativ konstant blieben und offenbar die wichtigsten physikochemischen Determinanten sind.

A 1-Norbornene Adduct of a Transition Metal and an Electrochemical Study of the Bridgehead Olefin Complex

“…While bridgehead double bonds in larger ring systems are known to be relatively stable, the existence of smaller ring systems with bridgehead double bonds such as 1-norbornene ( 1 ) has been harder to evaluate, as Wiseman predicted that the strain in bridgehead alkenes is closely related to the strain of the corresponding trans -cycloalkene . Indirect evidence of the anti-Bredt olefin 1 has been obtained by trapping transiently generated 1 with a variety of organic reagents or by monitoring the thermal rearrangement products of precursor derivatives. − A number of computational methods have also been applied to 1 in order to better understand the structure, energetics, and reactivity of this highly sensitive molecule. − However, as no direct observation of 1 in solution has ever been reported and no reversible trapping agent for this molecule has ever been prepared, its chemistry has been difficult to study.…”

“…11 Indirect evidence of the anti-Bredt 12 olefin 1 has been obtained by trapping transiently generated 1 with a variety of organic reagents or by monitoring the thermal rearrangement products of precursor derivatives. [13][14][15][16][17] A number of computational methods have also been applied to 1 in order to better understand the structure, energetics, and reactivity of this highly sensitive molecule. [18][19][20][21][22][23] However, as no direct observation of 1 in solution has ever been reported and no reversible trapping agent for this molecule has ever been prepared, its chemistry has been difficult to study.…”

The Application of Cyclobutane Derivatives in Organic Synthesis

“…Szeimies and coworkers promoted this notion by constructing a 1-norbornene skeleton. (4-Bromo-1-bicyclo[2.1.1]hexyl)bromo carbene (120) was generated from 119 by metalation with sodium bis(trimethylsilyl)amide in Et 2 O in the presence of diphenylisobenzofuran in a temperature range of −15 to 20 • C. As expected, 120 rearranged with enlargement of the four-membered ring to give 2,4-dibromobicyclo[2.1.1]hept-1-ene (121) which was accordingly trapped by diphenylisobenzofuran 47 .…”

Bridgehead Substitution via Putative Norborn‐1‐en‐3‐ones: Application in the Synthesis of Complex Molecules

“…Barton and coworker8d obtained nortricyclene via generation and rearrangement of 1‐norbornene. Szeimies and coworkers8e trapped 1‐norbornene through rearrangement of bicyclo[1.1.1]pentyl carbenes with isobenzofuran and it was trapped by complexing with nickel through β‐hydride elimination 8f. However, even with these advances, strong and convincing evidence for the existence of bridgehead CC bond in bicyclo[2.2.1]heptene system is still lacking.…”