Concerted Grob Fragmentation in N-Halo-.alpha.-amino Acid Decomposition

Abstract

The Grob fragmentation of -halo-a-amino acids in aqueous solution has been studied, being first order in TV-halo-a-amino acid and pH-independent. The substituents on the C2 and N atoms strongly affect the reaction rate. Structure reactivity correlations for C2 substituents provide * values of -3.9 and -4.1 for N-Cl and -Br compounds, respectively. The same correlations for N substituents lead to * values of -2.1 and -1.9 for -Cl and -Br compounds. The transition state (TS) can be generally described as product-like, its structure and characteristics being significantly affected by the substituents on the C2 and on the N atoms. In conclusion, the reaction is a DEDN concerted and slightly nonsynchronous two-stage process.

The Aldol‐Grob Reaction: Regioselective Synthesis of (E)‐Alkenes from Aldehydes and Ketones with Ytterbium Triflate Catalysis

“…Lower temperatures or shorter reaction times resulted in lower yields which were shown to be not significantly dependent on the position and electronic properties of the aryl substituent, except for nitro Table 1. Reaction between aldehydes and ketones catalysed by Yb(OTf) 3 [a] Isolated yield.…”

“…The reaction to give alkene 1 was in fact repeated three times, washing the catalyst with CH 2 Cl 2 and drying it at 70°C for two hours after each run, with the following yields: 83%, 81% and 81%. Therefore the concomitant formation of a carboxylic acid as a reaction product, capable of rendering Yb(OTf) 3 ineffective as an aldolGrob catalyst (by chelation), does not significantly affect its catalytic activity.…”

“…The absence of solvents seems to be crucial in driving the process to yield the aldol-Grob adduct, while the presence of solvents like THF, alcohols or water leads to the formation of only aldol condensation products (α,β-unsaturated ketones) and the use of dichloromethane, n-hexane or toluene greatly decreases the catalytic activity of Yb(OTf) 3 ; starting materials were recovered in almost quantitative yield.…”

“…In this paper we have shown that Yb(OTf) 3 hydrate is an effective catalyst in promoting the reaction between ketones and aromatic aldehydes, affording only (E)-alkenes. The main difference in our methodology compared to BF 3 -catalysed reactions is the Lewis acid/substrate ratio, the optimal value of which was found to be 0.1:1; in the other cases a 1:1 ratio or even an excess of Lewis acid is needed to effectively promote the coupling reaction.…”

“…[1] The initial product of this reaction is a β-hydroxycarbonyl compound, which, in turn, can be transformed either into an α,β-unsaturated carbonyl compound, via dehydration, or into an alkene by a mechanism similar to the Grob fragmentation [2] of N-halo-α-amino acids, [3] cyclobutanone hemiacetals [4] and β-hydroxy acetals [5] used for the synthesis of medium-sized carbocycles, [6] pharmaceuticals [7] and carbohydrates. [8] In 1993 Sakai [9] and co-workers described a novel BF 3 etherate catalysed one-pot tandem aldol condensationGrob fragmentation sequence.…”