2-mercaptobenzaldehydes

Novel aldol-type reactions under Cinchona-deriwed chiral thiourea catalysis was reported by Wang et al. [78]. In their report, a novel cascade Michael-aldol reaction was presented. The reaction involves a tandem reaction catalyzed via hydrogen-bonding with as little as 1 mol% catalyst loading to generate a product with three stereogenic centers (Scheme 28). hi the reaction of 2-mercaptobenzaldehyde 128 and a,P-unsatnrated oxazolidinone 129, the desired benzothiopyran 130 was formed smoothly in high yield and excellent stereoselectivity. 

The asymmetric conjugate additions with thiol nucleophiles was further expanded to 2-mercaptobenzaldehydes [98]. Wang had previously developed a domino Michael-aldol reaction promoted by Cinchona alkaloids, and now illustrated the utihty of cyclohexane-diamine bifunctionalized catalysts for the domino... 

Michael-aldol for 2-mercaptobenzaldehydes and maleimides. Use of catalyst 166 provided a variety of fused heterocycles in high yield and high enantiomeric ratios (Scheme 44). The authors propose that the chiral catalyst simultaneously activates the thiol and the maleimide via Brpnsted base and acid interactions. It was proposed that the pre-transition state arrangement of the catalyst and substrates determines the stereochemical outcome. 

Scheme 6.71 Succinimide-containing substituted thiochromanes obtained from the 12-catalyzed enantio- and diastereoselective domino Michael-aldol reaction between 2-mercaptobenzaldehydes and maleimides.

In 2007, Wang and co-workers published a protocol for an enantio- and diastereoselective domino Michael-aldol reaction using electron-rich and electron-deficient 2-mercaptobenzaldehydes and maleimides as substrates [223]. The conversion was described to proceed smoothly in the presence of bifunctional catalyst 12 (lmol% loading) in xylenes at 0°C reaction temperature producing the desired chiral succinimide-containing substituted thiochromanes 1-5 in high yields (83-96%), in synthetically useful ee values (74—94%), and diastereoselectivities (up to dr 20 1) in 7h reaction time (Scheme 6.71). 

Scheme 6.130 Proposed mechanism of the 121-catalyzed enantioselective thio-Michael-aldol tandem reaction of 2-mercaptobenzaldehydes with a,P-unsaturated oxazolidinones bifunctional activation through thiourea 121.

Scheme 6.131 Typical thiochromanes obtained from the 121-catalyzed asymmetric thio-Michael-aldol tandem reaction between various 2-mercaptobenzaldehydes and a, 3-unsaturated oxazolidinones.

Scheme 6.144 Thiochromanes prepared from the 121-catalyzed enantioselective tandem Michael-Knoevenagel reaction between 2-mercaptobenzaldehydes and diethyl methylenemalonates. The product configurations were not determined.

Although 2-mercaptobenzaldehyde (6) is an unstable intermediate, prone to resinification on storage, a surprising amount of research has been conducted using it as a source of thiocoumarins, with many workers preferring to use it directly or store it in solution at 0°C or below. It was first synthesized by Friedlander and Lenk in 1912 (Scheme 5). °... 

In Section II,B several cinnamic acid derivatives were prepared from 2-mercaptobenzaldehydes and the corresponding ketones. These were cyclized either in situ or separately to give thiocoumarins. An alternative synthetic approach introduces the mercapto group as the last stage by way of a... 

The asymmetric domino reactions between 2-mercaptobenzaldehyde and a,fi-unsaturated aldehydes proceed with excellent chemo- and enantio-selectivities in the presence of (99) (20 mol%) as organocatalyst to afford 2//-l-benzothiopyrans (98) in high yields with 91-98% ee.145... 

Schiff bases of 2-mercaptobenzaldehyde, which can be used as ligands to obtain ICC of type 467, are unstable for this purpose. So, the stable compounds 469 are mostly used as ligands for the syntheses of chelates 467 an alternative way for their synthesis is carried out through the method of template synthesis starting from thiosali-cylialdehydates 470 (see Sec. 3.3 on template syntheses) ... 

The asymmetric domino reaction between 2-mercaptobenzaldehyde and a,f)-unsaturated aldehydes proceeds with excellent chemo- and enantio-selectivities to afford 2-substituted 3-formyl-2//-l bcnzothiopyrans, products of a formal Baylis-Hillman reaction, when the. 9-proline derived catalyst 407 is employed (Scheme 123) <2006TL8547>. 

Another ready source of a suitable 2-mercaptobenzaldehyde derivative... 

Wang and coworkers found that the quinine-derived thiourea catalyst 81b (1 mol%) was also highly reactive and enantioselective for the tandem thio-Michael-aldol reaction of various 2-mercaptobenzaldehydes (103) with a,P-unsaturated oxazolidi-nones (104), furnishing benzothiopyranes (105) with three stereogenic centers in... 

Electron-deficient hydroxyimine (134 R = NO2) reacts with 5-nitro-2-mercaptobenzaldehyde to afford bridged dibenzo compound (128) more electron-rich imines (e.g. 134 R = H, Br) do not yield oxathiocins (Equation (45)) <92JOU33i>. 

The process was efRciently catalyzed by a chiral pyrrolidine in the presence of salicylic acid. It must be noted that Zhao et al. [159] had previously developed, in 2007, a similar reaction for the synthesis of chiral thiochromanes through domino oxa-Michael/Henry reaction of 2-mercaptobenzaldehydes with ititrostyrenes catalyzed by a simple chiral cupreine. The corresponding chiral 2-aryl-3-ititrothiochroman-... 

Wang et al. [49] obtained enantioenriched thiochromenes through a cascade sulfa-Michael-aldol-dehydration reaction between 2-mercaptobenzaldehydes and a,p-unsaturated aldehydes, catalyzed by 17a (Scheme 14.17a). Cordova and coworkers [50] obtained comparable results despite some minor changes of the reaction conditions. An analogous process with cyclic enones afforded tetrahydrothioxanthe-nones in only moderate enantioselectivities (Scheme 14.17b). In this case, chiral pyrrolidines 18 and 19 gave the best results in terms of enantioselectivities [51]. 

Mercaptobenzaldehyde Condensation of this auxiliary with a terminal amine gives an acid stable benzyl amine, but leaves... 

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