Diazirines:  Carbene Precursors Par Excellence

Abstract

Diazirines are prime precursors for carbenes. In this Account, we discuss the synthetic and mechanistic dimensions that govern the range, availability, and utility of diazirines. We focus on the Graham reaction, which affords halodiazirines from amidines in a one-pot procedure, and the diazirine exchange reaction, which allows easy replacement of an initial diazirine's halo substituent by a variety of other nucleophiles. Together, the Graham reaction and the diazirine exchange reaction provide an extraordinarily wide range of diazirine precurors for electrophilic, ambiphilic, and nucleophilic carbenes.

A Half‐Century Odyssey in the Realm of Reactive Intermediates

“…These "simple" substitution processes probably occurred through successive S N 2' reactions. [33] Alkylhaloand alkoxyhalodiazirines underwent analogous exchange reactions [Reaction (2)].…”

Three‐Membered Heterocycles. Structure and Reactivity

“…Diazirines with leaving groups at the 3-position can undergo substitution reactions without affecting the azo moiety [750]. As one example, the bromodiazirine 769 (Scheme 2.111) is converted into the fluoro analog 770 upon treatment with anhydrous tetrabutylammonium fluoride (TBAF) under solvent-free conditions [751].…”

Synthesis and application of photoproline - a photoactivatable derivative of proline

“…The solution was acidified to pH 2 and the product was extracted with ethyl acetate (4 × 50 ml). The organic phase was washed once with brine and dried over Na 2 …”

“…One of the most versatile photolabile groups for this purpose is the diazirine, due to its small size, and efficient and irreversible formation of a reactive carbene upon excitation at 350 nm. 2,3 Amino acid-based photoaffinity probes, including the phenylalanine analogues p-benzoylphenylalanine, p-azidophenylalanine and 4-[3-trifluoromethyl]-3H-diazirin-3-yl]-phenylalanine have been known for some time, [4][5][6] and more recently the alkyldiazirine amino acid analogs photoleucine, and photomethionine have been described. 7,8 Here we describe the synthesis and application of a related alkyldiazirine derivative of proline (photoproline), containing a diazirine group at position-4 of the pyrrolidine ring.…”