2,4-Bis(fluorocarbon)-substituted phenols for high yield Newman–Kwart rearrangement reactions (original) (raw)
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Angewandte Chemie International Edition, 2009
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).
Tetrahedron, 2013
The synthesis of polydentate amine-S-arythiocarbamates was tested by directed ortho-lithiation of 2,4disubstituted thiophenols, or the corresponding O-and S-arylthiocarbamates by deprotonation or lithiumebromine exchange, followed by addition of the electrophiles N(CH 2 CH 2 X) 3 (X¼Br, I). In the case of the thiophenol, deprotonation resulted in a trithioether-amine upon addition of the electrophile. With the O-and S-thiocarbamates, the reactions resulted in the migration of the thiocarbamoyl group to the ortho-position (Fries rearrangement), or nucleophilic attack of the carbonyl group by butyllithium, respectively. An alternative route employed 2,4-disubstituted phenols to obtain the corresponding salicylaldehydes, and subsequently the O-arylthiocarbamates for NewmaneKwart thermal rearrangement (NKR). Finally, the formyl group on the S-arylthiocarbamates allowed reductive amination to assemble polytopic compounds with amine and S-thiocarbamate groups.
Synthesis of 2,4-disubstituted thiophenols and solid state structures of thiocarbamate precursors
Journal of the Brazilian Chemical Society, 2005
quais mostram diferentes graus de impedimento estérico na posição 2, foram preparados a partir dos correspondentes fenóis. Uma despronotação inicial dos fenóis foi obtida com o uso de NaH em dimetoxietano, seguido de tratamento com cloreto de N,N-dimetiltiocarbomoila, obtendo-se os O-ariltiocarbamatos. A termólise destes compostos resultou num rearranjo, obtendo-se os S-ariltiocarbamatos. Finalmente, a redução dos Sariltiocarbamatos com LiAlH 4 em THF, seguido de acidificação, levou ao isolamento dos tiofenóis. Todos os produtos foram caracterizados por técnicas espectroscópicas, e para alguns tiocarbamatos a estrutura sólida foi determinada por difração de raio X.
Advanced Synthesis & Catalysis, 2016
The first metal/photocatalyst-free, visible light induced chemoselective rearrangement of gketo acrylate thioesters via elusive thiyl radical migration is described. Thioesters bearing at least one alkyl substitution undergo 1,2-thiyl radical migration, whereas 1,4-migration has been observed when the substrate is substituted by aromatics only. The reactions show excellent functional group tolerance and are proposed to proceed through the trans-cis isomerization/intramolecular lactonization/thiyl radical capture pathway. This atom-economical process constitutes an efficient and practical method for the formation of substituted butenolides.
ChemistrySelect, 2016
An unexpected reactivity of the O-dimethylthiocarbamate function has been evidenced concomitantly with the reduction of an aldehyde function presents at its ortho (o-) position. A systematic study using various substrates showed the exclusive formation of the rearranged compounds after 24 h and confirmed that the only-reduced compounds are reaction intermediates. However, electronic/steric contributions of the aromatic ring substituents on the composition of the reaction mixture (reduction of the aldehyde vs. migration) were observed at the early stage of the reaction (2 h). These new benzyl S-thiocarbamates compounds could be of particular interest as precursors for not trivial and functionalized free methylthiobenzyl alcohols.
The Journal of Organic Chemistry, 2000
The reaction of a series of ketones with dimsylsodium in dimethyl sulfoxide resulting in the formation of γ-unsaturated thiols was studied experimentally. [2,3]-Sigmatropic rearrangements of-unsaturated sulfinyl carbanions are involved at the key step of those transformations. DFT computations at the B3LYP/6-31+G* level indicated that such rearrangements, as well as some typical [2,3]-sigmatropic rearrangements, e.g., thermal rearrangements of allyl sulfoxides and Wittig rearrangements of sulfur ylides and lithiated allyloxy methyl anions, are concerted and moderately synchronous processes. Negative (diatropic) nucleus-independent chemical shifts (NICS) and high diamagnetic susceptibility exaltations indicate that the transition structures of these [2,3]sigmatropic migrations are aromatic.