Acid Catalyzed Alcoholysis of Sulfinamides: Unusual Stereochemistry, Kinetics and a Question of Mechanism Involving Sulfurane Intermediates and Their Pseudorotation

Abstract

The synthesis of optically active sulfinic acid esters has been accomplished by the acid catalyzed alcoholysis of optically active sulfinamides. Sulfinates are formed in this reaction with a full or predominant inversion of configuration at chiral sulfur or with predominant retention of configuration. The steric course of the reaction depends mainly on the size of the dialkylamido group in the sulfinamides and of the alcohols used as nucleophilic reagents. It has been found that bulky reaction components preferentially form sulfinates with retention of configuration. It has been demonstrated that the stereochemical outcome of the reaction can be changed from inversion to retention and vice versa by adding inorganic salts to the acidic reaction medium. The unusual stereochemistry of this typical bimolecular nucleophilic substitution reaction, as confirmed by kinetic measurements, has been rationalized in terms of the addition-elimination mechanism, A-E, involving sulfuranes as intermediates which undergo pseudorotations.

Nucleophilic Substitution at Tetracoordinate Sulfur. Kinetics and Mechanism of the Chloride-Chloride Exchange Reaction in Arenesulfonyl Chlorides: Counterintuitive Acceleration of Substitution at Sulfonyl Sulfur by ortho-Alkyl Groups and Its Origin

“…With regard to the sulfonyl transfer reactions, The major part of extensive investigations on nucleophilic substitution at tricoordinate sulfur compounds was devoted to the stereochemistry-mechanism relationship since these compounds are intrinsically chiral and are known in enantiomeric forms. Our recent results on the acid-catalyzed alcoholysis of sulfinamides and unusual stereochemistry of this reaction are the best illustration of these studies [9]. On the contrary, since the majority of tetracoordinate sulfur compounds are achiral, as for example sulfonyl derivatives, the parallel studies on substitution at the S IV -center were mainly concentrated on the kinetics of these reactions and mechanistic implications of the measurements performed.…”

Nucleophilic Substitution at Tetracoordinate Phosphorus. Stereochemical Course and Mechanisms of Nucleophilic Displacement Reactions at Phosphorus in Diastereomeric cis- and trans-2-Halogeno-4-methyl-1,3,2-dioxaphosphorinan-2-thiones: Experimental and DFT Studies

“…This reaction, as other reactions of P III -compounds with sulfenyl chlorides [19], gave the desired product 6(Cl) in a stereospecific way with retention of configuration at phosphorus via the intermediate quasi-phosphonium chloride (A). Hence, the isomer of 6(Cl) obtained has the same trans-relation between the C4-methyl group and the chlorine atom as in the starting phosphorochloridite (7).…”

“…Moreover, these three different TBPIs may be formed as primary intermediates or as a result of their pseudorotation. In this connection, it is necessary to emphasize a great importance of the Westheimer's concept [6] and his rules (apical entry of N, apical departure of L, microscopic reversibility and pseudorotation of TBPI) for understanding many aspects of nucleophilic substitution at phosphorus as well as at other heteroatoms such as sulfur [7]. The results of his careful studies on acid-catalyzed bidirectional hydrolysis of methyl ethylene phosphate 3 (2-methoxy-1,3,2-dioxaphospholan-2-one) and the concurrent rapid 16 O/ 18 O oxygen exchange in the phosphoryl group of 3 provided arguments for the A-E mechanism involving transient formation of a trigonal bipyramidal intermediate (TBPI-a) with the five-membered ring occupying the energetically most favorable apical-equatorial position and its Berry pseudorotation (BPR).…”

Diastereoisomerically Pure, (S)-O-1,2-O-isopropyli dene-(5-O-α-d-glucofuranosyl) t-butanesulfinate: Synthesis, Crystal Structure, Absolute Configuration and Reactivity

“…This can be explained by the reaction sequence which is shown below in the Scheme 7 and by assumption that the intermediate 4C has a trigonal bipyramidal structure. According to this mechanistic proposal, discussed in details in our recent paper [ 34 ], the observed inversion of configuration is caused by the presence of both the entering t -butyl substituent and the leaving O -α- d -glucofuranosyl group in the apical positions of this intermediate. This mechanistic proposal (in which we assume the monomeric nature of t -butylmagnesium chloride) also explains why the regioisomeric t -butanesulfinate 12 , the formation of which, via the intermediate 4E , is shown in the upper part of Scheme 7 was not observed in all experiments carried out in THF, Et 2 O, nor benzene.…”