Kinetic studies on the stability and reactivity of beta-amino alkylzinc iodides derived from amino acids.
Beta-amino alkylzinc iodides are intrinsically unstable toward beta-elimination and protonation. The aim of this study was to determine the rates of these processes and also to understand how the reactivity of a range of beta-amino alkylzinc iodides in Negishi cross-coupling reactions is influenced by the presence of functional groups within the zinc reagent. Decomposition of beta-benzamido alkylzinc iodides occurs by protonation, and the first-order rate constant for the self-protonation of the carbon-zinc bond in reagent 4b was determined to be 5.2 x 10(-6) s(-1) (at 291 K). In contrast, the carbamate derivative 2 decomposes by a first-order elimination process. The homologous reagent 3, derived from glutamic acid, decomposes more quickly by beta-elimination, with a first-order rate constant of 24 x 10(-6) s(-1) (at 291 K). Reagents 23 and 25, in which the Boc group has been replaced with a trifluoroacetyl group, are more stable toward beta-elimination than the corresponding reagents 2 and 3, a striking outcome given that the trifluoroacetamido group is a better leaving group. Moreover, this replacement also changes the mechanism of the elimination to a second order process. Pseudo-second-order rate constants for the Negishi cross-coupling of reagents 2, 3, 23, and 25 with iodobenzene have been determined, revealing the higher reactivity of the glutamic acid-derived reagents 3 and 25. The main factor influencing reactivity, therefore, is determined to be the proximity of the ester group, rather than the nature of the nitrogen protecting group. Finally, beta-amino alkylzinc iodides 46-48 containing Weinreb amides have been prepared, rate constants for their decomposition through elimination determined, and their synthetic potential for the preparation of beta-amino ketones established.
Rilatt
Ian
I
Department of Chemistry, The University of Sheffield, Dainton Building, Sheffield S3 7HF, United Kingdom.
Jackson
Richard F W
RF
D000588:Amines / Q000737:chemistry*; D000596:Amino Acids / Q000737:chemistry*; D001549:Benzamides / Q000737:chemistry; D002264:Carboxylic Acids / Q000737:chemistry; D007202:Indicators and Reagents / Q000737:chemistry; D007455:Iodine / Q000737:chemistry*; D007700:Kinetics; D009942:Organometallic Compounds / Q000737:chemistry*; D015032:Zinc / Q000737:chemistry*
D000588:Amines; D000596:Amino Acids; D001549:Benzamides; D002264:Carboxylic Acids; D007202:Indicators and Reagents; D009942:Organometallic Compounds; D007455:Iodine; D015032:Zinc