The first direct preparation of chiral functionalised ketones and their synthetic uses

Lithium Halomethylcarbenoids: Preparation and Use in the Homologation of Carbon Electrophiles

“…In this particular iodomethyllithium‐based homologation of lactones, the stabilization of the carbenoid by means of an ethereal solvent seems to be not large enough, given the high density of additional oxygenated functionalities present in the substrates. This explanation is also consistent with previous studies by Barluenga involving unfunctionalized (i.e., without additional oxygenated groups) lactones, which could be easily homologated with dihalomethyllithiums in diethyl ether 25a…”

“…Further studies in the late 1980s and the early 1990s by Matteson24 and Barluenga25 pointed out the feasibility of reactions at −78 °C and, thus, it can be definitively assumed that such a temperature is a very good compromise between thermal stability and reactivity of carbenoids. This temperature is considered the optimal one for generating both chloromethyllithium and bromomethyllithium.…”

“…In initial studies by Villieras, s ‐BuLi19 was employed to accomplish the exchange reaction in the so‐called Trapp mixture (THF–Et 2 O– n ‐pentane, 75:15:10 v/v/v)30 at −115 °C. However, this lithium base, as shown in more recent studies, is the reagent of choice for performing deprotonations rather than exchange reactions31 and, thus, MeLi and n ‐BuLi have emerged as the optimal lithium sources 25b. In recent years, the commercially available MeLi–LiBr complex in Et 2 O has become an excellent reagent for generating chloromethyllithium 3a starting from chloroiodomethane 12 (Scheme ) 32…”

Synthesis and Synthetic Applications of α-Amino Ketones Derived from Natural α-Amino Acids

“…The first direct conversion of -amino esters intoamino-'-haloketones was reported in 1994 [13]. The authors reported an easy, direct, and general method to obtain, without racemisation, chlorinated -aminoketones.…”

Chemoselective Synthesis of N‐Substituted α‐Amino‐α′‐chloro Ketones via Chloromethylation of Glycine‐Derived Weinreb Amides

“…In addition to the above-mentioned protocols, the synthesis of non-arylated a-amino-a'-chloro ketones generally proceeds via two main reactions, via homologations using lithium carbenoids, [16][17][18][19][20][21][22][23] diazomethane, [24][25][26] or dimethyl sulfoxonium methylide, [27] or via Claisen condensations. [28,29] Although effective, the use of the explosive diazomethane eventually in stoichiometric amounts [30] impedes the development of such methods for large-scale preparations.…”