Pd-Catalyzed Acyl C–O Bond Activation for Selective Ring-Opening of α-Methylene-β-lactones with Amines

Abstract

A Pd-catalyzed ring-opening of β-lactones with various types of amines (primary, secondary and aryl) to provide β-hydroxy amides with excellent selectivity towards acyl C–O bond cleavage is reported. The utility of this protocol is demonstrated in an asymmetric kinetic resolution providing enantioenriched α-Methylene-β-lactones

Strain‐Driven Dyotropic Rearrangement: A Unified Ring‐Expansion Approach to α‐Methylene‐γ‐butyrolactones

“…In a line with our previous work, [15] the designed dyotropic rearrangement of α‐methylene‐β‐lactone 6 [19] was first conducted in toluene with Et 2 AlCl as promoter. The starting material was quickly consumed, resulting in only one isolated product in 34 % yield, which was determined to be 5/6‐spiro bicyclic MBL 8 (entry 1, Table 1).…”

“…Besides α‐methylene‐γ‐butyrolactones, we envisioned that the dyotropic reaction developed by us could also be applied to the synthesis of α‐alkylidene‐γ‐butyrolactones, another important structural motif found in natural products and drugs [1c] . As the proof‐of‐concept cases, α‐alkylidene‐β‐lactones S88 – S90 , readily prepared from the corresponding α‐methylene‐β‐lactones through cross metathesis reaction, [19] were evaluated under the optimal conditions. Gratifyingly, all of them underwent dyotropic reactions smoothly, giving rise to α‐alkylidene‐γ‐butyrolactones 88 – 90 in high yields and selectivity (Figure 5).…”

“…We anticipated that such tendency might be further enhanced in the current case because of the increased RSE and the involvement of a stabilized allylic carbocation intermediate. One the other hand, as a densely functionalized small ring system, α‐methylene‐β‐lactone could also engage in other transformations such as acyl C‐O cleavage, [19] Michael addition, [20] and decarboxylation reaction [21] . In this context, it would be challenging to achieve the expected dyotropic rearrangement without the interference of underlying side reactions.…”

α‐Methylene‐β‐Lactone Scaffold for Developing Chemical Probes at the Two Ends of the Selectivity Spectrum

“…4‐(But‐3‐ynyl)‐3‐methyleneoxetan‐2‐one ( 1 ) was synthesized according to published procedures, [24,38] and was used for both gel‐based and MS‐based reactivity characterization and competitive ABPP experiments. Preparation of MeLac‐treated proteome samples, proteomics profiling using LC‐MS/MS, data analysis, and docking of stereoisomers of GSH‐Lac‐Alkyne probe ( 4 ) to GSTP1 were described in the Supporting Information.…”

Ligand‐Controlled Palladium‐Catalyzed Carbonylation of Alkynols: Highly Selective Synthesis of α‐Methylene‐β‐Lactones

“…In organic chemistry, the high degree of functional groups in a compact manner allows diverse synthetic utilizations and makes this class of compounds interesting building blocks [3] . More specifically, owing to their inherent strain in the four‐membered ring, they readily undergo ring opening reactions with a wide range of nucleophiles by either acyl C−O or alkyl C−O bond cleavage [3f,g] . Besides the usual electrophilic sites of the carbonyl and oxetane carbon atoms contained in β‐lactones, Michael‐type additions of nucleophiles and radicals at the methylene carbon atom are feasible [3h] and offer attractive possibilities for preparative purposes.…”