Andersen synthesis

Amino acids, sulphoxide, radiolysis of 909 a-Amino acids, reactions of 776, 777 a-Aminosulphones, synthesis of 176 Aminosulphonyl radicals 1093 Aminosulphoxides rearrangement of 740 synthesis of 336 Andersen synthesis 60 / -Anilinosulphoxides, synthesis of 334, 335 Anion radicals 1048-1050 ESR spectra of 1050-1054 formation of during electrolysis 963 during radiolysis 892-897, 899, 903 Annulation 778, 781, 801, 802 Antibiotics, synthesis of 310 Arenesulphenamides 740 Arenesulphenates 623 reactions of 282 rearrangement of 719 Arenesulphinates 824, 959 chiral 618... 

The Andersen synthesis of chiral sulfoxides has also been extended to diastereomerically or enantiomerically pure arenesulfinamides, which on treatment with methyllithium give optically active methyl aryl sulfoxides (83,85). The use of menthyl sulfinates in the synthesis of sulfoxides has been exploited in the preparation of optically active sulfoxides 47 and 48, which are chiral by virtue of isotopic substitution, H- D (86), and (87), respectively. More recent... 

An alternative stereospecific synthesis of chiral sulfimides reported by Nudelman (137) consists of the reaction of the diastereomeric menthyl p-toluenesulfinimidoates 90 with Gri ard reagents giving the optically active sulfimide 91. This reaction, like the Andersen synthesis of chiral sulfoxides, proceeds with inversion of configura-... 

In the mid-1960s Mislow started a research program on the mechanism of the thermal racemization of sulfoxides [97-99]. In the course of these efforts he recognized an enormous racemization rate acceleration for (R)-allyl-p-tolyl sulfoxide ((R)-151) as compared to benzyl or, even more pronounced, to alkyl sulfoxides (Scheme 42). For this compound, prepared by Andersen synthesis [100,101], he found a racemization rate exceeding that of the phenyl-substituted sulfoxide by a factor of 560 000. Based on kinetic measurements Mislow et al. determined the activation parameters to be AH = 22 kcal mor ... 

There are several efficient methods available for the synthesis of homochiral sulfoxides [3], such as asymmetric oxidation, optical resolution (chemical or bio-catalytic) and nucleophilic substitution on chiral sulfinates (the Andersen synthesis). The asymmetric oxidation process, in particular, has received much attention recently. The first practical example of asymmetric oxidation based on a modified Sharpless epoxidation reagent was first reported by Kagan [4] and Modena [5] independently. With further improvement on the oxidant and the chiral ligand, chiral sulfoxides of >95% ee can be routinely prepared by these asymmetric oxidation methods. Nonetheless, of these methods, the Andersen synthesis [6] is still one of the most widely used and reliable synthetic route to homochiral sulfoxides. Clean inversion takes place at the stereogenic sulfur center of the sulfinate in the Andersen synthesis. Therefore, the key advantage of the Andersen approach is that the absolute configuration of the resulting sulfoxide is well defined provided the absolute stereochemistry of the sulfinate is known. 

Scheme 8.27. (a) An example of the Andersen synthesis of chiral sulfoxides [119]. (b) Catalytic oxidation of an aromatic sulfide using a chiral titanium complex [118]. fc) Synthesis of a C2-symmetrical fra s-l,3-dithiane-l,3-dioxide and its use as an asymmetric acyl anion equivalent [120,121]. 

Enantiopure sulfinimines are ammonia imine synthons useful in the asymmetric synthesis of amines and -amino acid derivatives. Sulfinimines unavailable via the Andersen synthesis (R = H) are prepared hy asymmetric oxidation of the sulfenimines, ArS-N=C(R)PhX, with (+)-( ) or (-)-(1) at -20 to 20 °C in CCI4 (eq 8). Crystallization improves the ee to >95%. The sulfoxide chiral recognition model correctly predicts the configuration of the product. 

A great achievement of the stereochemistry of organosulphur compounds was the stereoselective synthesis of optically active sulphoxides developed by Andersen in 1962342. This approach to sulphoxides of high optical purity, still most important and widely used,... 

The Andersen sulphoxide synthesis is general in scope and a large number of chiral alkyl aryl and diaryl sulphoxides became available from (—)-(S)-276 and other optically active sulphinates343-346 (Table 16). 

Further utility of the Andersen sulphoxides synthesis is demonstrated by the preparation of optically active unsaturated sulphoxides which were first prepared by Stirling and coworkers359 from sulphinate 276 and the appropriate vinylic Grignard reagents. Later on, Posner and Tang360 prepared in a similar way a series of ( )-l-alkenyl p-tolyl sulphoxides. Posner s group accomplished also the synthesis of (+)-(S)-2-(p-tolylsulphinyl)-2-cyclopentenone 287, which is a key compound in the chiral synthesis of various natural products361 (equation 159). 

The Andersen sulphoxide synthesis allows one also to synthesize a variety of a-heteroatom substituted sulphoxides starting from a-heteroatom stabilized carbanions and (—)-(S)-276. The selected examples shown in Scheme 3 are the best illustration of the generality of this approach. The reaction of enolates or enolate like species with (—)-(S)-276 has been used for the synthesis of optically active a-carbalkoxy sulphoxides. For example, treatment of (—)-(S)-276 with the halogenomagnesium enolates of -butyl acetate, t-butyl propionate or t-butyl butyrate resulted in the formation of ( + )-(R)-t-butyl p-toluenesulphinylcarboxylates 298367 (equation 163). 

Laroche L, Bekiaris N, Andersen HW and Morari M (1992) Homogeneous Azeotropic Distillation Separability and Flowsheet Synthesis, Ind Eng Chem Res, 31 2190. 

Knutsen, L. J., Andersen, K. E., Lau, J., et al. (1999) Synthesis of novel GABA uptake inhibitors. 3. Diaryloxime and diarylvinyl ether derivatives of nipecotic acid and guvacine as anticonvulsant agents. J. Med. Chem. 42, 3447-3462. 

Andersen, K. E Lau, J., Lundt, B. F Petersen, H Huusfeldt, P. 0., Suzdak, P. D., and Swedberg, M. D. (2001) Synthesis of novel GABA uptake inhibitors. Part 6 preparation and evaluation of N-Omega asymmetrically substituted nipecotic acid derivatives. Bioorg. Med. Chem. 9,2773-2785. 

The most important and widely used approach to chiral sulfoxides is the method developed by Andersen (5) based on the reaction between the diastereomerically pure (or strongly enriched in one dia-stereomer) menthyl arenesulfinates and Grignard reagents. The first stereospecific synthesis of optically active (+H7 )-ethyl p-tolyl sulfoxide 22 was accomplished in 1962 by Andersen (75) from (-)-(iS)-menthyl p-toluenesulfmate 45 and ethylmagnesium iodide. 

In addition to routes involving resolution and asymmetric synthesis, optically active sulfonium salts have been prepared in a stereospecific way by Andersen (158,159). Thus, synthesis of the optically active dialkyl-p-tolylsulfonium salts 114 from the optically active ethoxy-sulfonium salt 115 was accomplished by the addition of alkyl Grig-nard or dialkylcadmium reagents. This reaction occurs with inversion... 

Wendelbo, R., Akporiaye, D., Andersen, A., Dahl, I.M., and Mostad, H.B. (1996) Synthesis, characterization and catalytic testing of SAPO-18, MgAPO-18, and ZnAPO-18 in the MTO reaction. Appl. Catal. A, 142, L197-L207. 

Gotfredsen, S.E., Ingvorsen, K., Yale, B. and Andersen, O. (1985) The scope of biocatalysts in organic chemical processing. In Biocatalysts in Organic Synthesis, edited by J.Tramper, H.C.van der Plas and P.Linko, pp. 3-18. Amsterdam Elsevier. 

T. Ruhland, K. Andersen and H. Pedersen, Selenium-linking strategy for traceless solid-phase synthesis Direct loading, aliphatic C-H bond formation upon cleavage and reaction monitoring by gradient MAS NMR spectroscopy, J. Org. Chem., 1998, 63, 9204-9211. 

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