Thermally induced O Ar !S Ar migration in aryl thiocarbamates (1!2, Scheme 1) [1] is commonly referred to [2] as the Newman-Kwart rearrangement ("NKR") [3] and belongs to a group of rearrangements that generate Ar-S/N compounds from phenols. [4] Of these, only the NKR has been extensively utilized, [1] with applications as broad-ranging as medicinal chemistry, [5] chiral ligand synthesis, [6] supramolecular chemistry, [7] molecular switches, [8] molecular rods, [9] dendrimers, [10] organocatalysts [11] and helicenes. [12] The NKR has also been applied industrially, [1,5] more recently by applying microwave [13, 14a] and flow-reactor technologies. [14] There are many favorable aspects to NKR, [1] including: 1) the facile generation of 1 from the corresponding phenol, a moiety that is readily accessible and is often commercially available; [15] 2) simple hydrolysis of 2 liberates the thiol, ArSH; 3) the thiocarbamate group provides both the Ar-O activation and the source of sulfur-no additional reagents are required; and 4) 1 and 2 are usually highly crystalline, [13c] aiding handling and purification.
The one major drawback to NKR is that high temperatures (200-300 8C) are required to access the strained 1,3oxathietane transition state (see mechanism A, [1,16] Scheme 2). Not only do such high temperatures present issues in terms of practicality and safety, but they can also induce "charring" and other undesired side reactions, meaning that fragile substrates are not amenable to the harsh reaction conditions. [17] Clearly any significant reduction in reaction temperature would be advantageous. Herein we report on the development of the first catalyst [18, 19] for the NKR 1!2, facilitating rearrangement at substantially lower temperatures.
We considered two distinct approaches to facilitate catalysis of the reaction. In the first (B, Scheme 2) a p-acid "M" could be used to increase the electrophilicity of the aryl ring, thus lowering the barrier to 1,3-oxathietane generation. [16, 18] Choosing one of the most active substrates for NKR, X = p-NO 2 (1 a) which undergoes thermal NKR at 180 8C, [3b] a range of cationic and neutral Lewis acids were explored in this regard and whilst some success was obtained with Ni and Mg complexes, the catalytic effects were specific to 1 a [20] suggesting that activation is by complexation to the NO 2 group, [21, 22] not to the aromatic ring p-system.
We then explored an alternative strategy [18b] (C) in which the Ar À O bond is cleaved by insertion of a low-valent metal "M", with the thiocarbamate tautomer facilitating reductive elimination of M as the new ArÀS bond is formed. Given the known oxidative addition of Pd 0 complexes to arylsulfonates, [23] we tested a range of simple phosphine ligands in combination with 10 mol % Pd 0 in N,N-dimethylacetamide at 70 8C (P/Pd = 2). Of these ligands, tBu 3 P was uniquely effective, giving rise to 47 % 2 a after 24 h. The effect of solvent was then explored and from N,N-dimethylacetamide, MeCN, CH 2 Cl 2 , THF, PhCF 3 and toluene, the latter was found to be by far the most effective, allowing quantitative conversion of 1 a at 100 8C in 2.5 h with just 2 mol % Pd (Scheme 3, and Table 1, entries 1-4). In the absence of catalyst, there was no detectable rearrangement.
The [Pd(tBu 3 P) 2 ] catalyst was tested with a small range of simple aryl thiocarbamates (1 a-h, 100 8C, toluene, Table 1, entries 5-11). In all cases rearrangement was catalyzed, allowing NKR at a substantially lower temperature than Scheme 1. Classic thermal Newman-Kwart rearrangement (NKR). [1,2] Scheme 2. Strategies for catalysis (B, C) of the thermal NKR (A).