We have developed an efficient water-solvent method for p-toluenesulfonylation (tosylation) and methanesulfonylation (mesylation) of primary alcohols using p-toluenesulfonyl chloride and methanesulfonyl chloride, respectively, promoted by KOH and catalytic amines. The reaction was performed by maintaining the pH at around 10 using a pH controller to prevent the undesirable decomposition of sulfonyl chlorides. Several primary alcohols were smoothly sulfonylated in excellent yield. The choice of the amine catalyst (0.1 equiv.) was important: N,Ndimethylbenzylamine, a sterically unhindered and lipophilic tertiary amine, was effective for the tosylation, whereas N,N-dimethylbutylamine and triethylamine were effective for the mesylation. The present Schotten-Baumann-type method is the first example of catalytic sulfonylation using sulfonyl chlorides, and is a green chemical process due to the use of water as the solvent.

[reaction: see text] An efficient synthesis of highly substituted alpha-arylnaphthalene analogues has been developed utilizing Lewis acid-promoted regiocontrolled benzannulation of aryl(aryl')-2,2-dichlorocyclopropylmethanols (aryl not equal aryl'; abbreviated as AACMs). Both AACM diastereomers were easily prepared via highly stereoselective addition (>95/5) of ArLi to gem-dichlorocyclopropropyl aryl' ketones. The choice of Lewis acids determined the cyclization regioselectivity of the present benzannulation. TiCl4 and SnCl4 used the chelation pathway, whereas silyl triflates used a nonchelation pathway to give unsymmetrically substituted regioisomeric alpha-arylnaphthalenes in 40-91% yields with moderate to excellent regioselectivity (TiCl4 or SnCl4; >99/1-3/1, TBDMSOTf; >1/99-1/4). Thus, the alpha-aryl or alpha-aryl' moiety (accessory aryl group) was alternatively introduced to alpha-arylnaphthalenes by choosing either the order of the reaction sequences or the appropriate catalyst. Application of the present method to the total synthesis for unsymmetrically substituted natural lignan lactones, justicidin B, retrojusticidin B, dehydrodesoxypodophyllotoxin, and a related analogue, 5'-methoxyretrochinensin, was demonstrated. Lignan retrolactones (retrojusticidin B and 5'-methoxyretrochinensin) were synthesized by the conventional lactonization of the diol precursor, whereas a novel Bu2SnO-mediated monoacylation method was applied to the synthesis of normal lignan lactones (justicidin B and dehydrodesoxypodophyllotoxin).

An efficient method for esterification between acid chlorides and alcohols in water as solvent has been developed by combining the catalytic amines, N-methylimidazole and N,N,N',N'-tetramethylethylenediamine (TMEDA). The present Schotten-Baumann-type reaction was performed by maintaining the pH at around 11.5 using a pH controller to prevent the decomposition of acid chlorides and/or esters and to facilitate the condensation. The choice of catalysts (0.1 equiv.) was crucial: the combined use of N-methylimidazole and TMEDA exhibited a dramatic synergistic effect. The catalytic amines have two different roles: (i) N-methylimidazole forms highly reactive ammonium intermediates with acid chlorides and (ii) TMEDA acts as an effective HCl binder. The production of these intermediates was rationally supported by a careful 1 H NMR monitoring study. Related amide formation was also achieved between acid chlorides and primary or secondary amines, including less nucleophilic or water-soluble amines such as 2-(or 4-)chloroaniline, the Weinreb N-methoxyamine, and 2,2-dimethoxyethanamine.