T-butylsulfinates

The Mikolajczyk group36 has developed use of natural alkaloids as chiral catalysts in conversion of symmetrical dialkyl sulfites into alkyl t-butylsulfinate esters in 40-70% enantiomeric purity (equation 6). 

Whereas Pd-catalyzed asymmetric allylic substitution reactions, with carbon as well as with heteronucleophiles, are widespread in stereoselective catalysis, it seems unusual that sulfur nucleophiles are less commonly used. Therefore we tested our ligands in such a reaction. We employed ligands 2 and 3 successfully in the reaction of racemic 3-methoxycarbonyloxyhept-4-ene with lithium t-butylsulfinate in the presence of 1.5 mol% of Pd2dba3 and 4.5 mol% of the ligands. In all cases full conversion was achieved, but with marked differences in the product selectivities (Scheme 1.4.9, Table 1.4.7). 

Next the kinetic resolution of the acyclic carbonate roc-3aa by using lithium t-butylsulfinate in the presence of Pd(0)/L (1.5 mol%) and BPA (4.5 mol%) was studied (Scheme 2.1.4.4). Both kinetic resolution and enantioselective substitution occurred in this case with high selectivities and gave the carbonate ent-Saa and sulfone 4aa in good yields (Table 2.1.4.3). 

Scheme 2.1.4.4 Pd(0)/BPA-catalyzed kinetic resolution of an acyclic carbonate with lithium t-butylsulfinate.

Calculation of S for the kinetic resolution of the cyclohexenyl carbonate rac-laa with 2-pyrimidinethiol and lithium t-butylsulfinate according to Eq. (1) gave large values for pairs of ee versus c (compare Tables 2.1.4.5 and 2.1.4.6). This is in accordance with the isolation of ent-laa with a high ee at approximately 50% conversion in the preparative experiments (compare Tables 2.1.4.1 and 2.1.4.4). However, Tables 2.1.4.5 and 2.1.4.6 also reveal major and irregular changes of S with conversion. Since our measurements of ee and c had a precision of only 0.5% and 1.0%, respectively, we ascribe the change of S with conversion mainly to errors in the determination of both values. 

The racemic acyclic allylic t-butylsulfinates roc-llaa and roc-llba were prepared both as 1 1 mixtures of diastereomers from the racemic allylic alcohols rac-lOa and roc-lOb, respectively, and racemic 2-t-butylsulfinyl chloride [18], in high yields (Scheme 2.1.4.13). 

The Pd-catalyzed rearrangement of the acyclic S-t-butylsulfinates roc-llaa and rac-llba proceeded quantitatively at room temperature and gave the allylic sulfones 4aa and 4ba with high enantioselectivities in high yields (Scheme 2.1.4.14 and Table 2.1.4.11, entries 1 and 2) [17]. 

Preparation of Chiral Sulfinates. Optically active sulfinates can be prepared by reaction of a symmetrical sulfite with t-Butylmagnesium Chloride in the presence of an optically active amino alcohol. The best enantioselectivity has been observed using quinine as the optically active amine (eq 2)3 An alternative approach to this new enantioselective asymmetric synthesis of alkyl t-butylsulfinates would be reaction of a racemic sulfinate with r-butylmagnesium chloride complexed by optically active alkaloids (eq 3). In this case, kinetic resolution of the racemic sulfinate leads to an optically active sulfinate and an optically active sulfoxide. 

Ethylsulfine (propanethial 5-oxide) was spectroscopically identical to the natural onion lachrymatory factor . The configuration of the natural ethylsulfine was established to be Z by the anisotropic deshielding effect of the CSO group on the C(l)-H in combination with benzene induced shifts . The lachrymatory effect of sulfines diminishes when the substituent is more bulky t-butylsulfine is devoid of lachrymatory activity. Also, 2,3-dimethylbutanedithial 5 ,5 -dioxide, a disulfine, was isolated from an onion extract . 

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