Synthesis and Stereoselective Reactions of (R)‐α‐Sulfonyloxynitriles

Abstract

0 VCH Verlagsgesellschaft synthetic potential of optically active cyanohydrins by conversion of the hydroxy group into a good leaving group. Of particular interest are reactions of the cyanohydrin derivdtives in which the nitrogen of the cyano group remains in the molecule, since compounds of this type are not directly accessible via cr-amino-or a-hydroxycarboxylic acids.Whereas stereoselective nucleophilic substitution in the a-position of carboxylic acids and carboxylates presents few diffi~ulties,[~] very little is known about a corresponding reaction of a-substituted nit rile^. [^] Starting from optically active nitriles with a leaving group in the a-position, only crhalonitriles have so far been prepared,r4' but these readily racemize in the presence of halide ions liberated in substitution rea~tions.[~"1 Optically active a-sulfonyloxynitriles, which should be considerably more stable configurationally on account of the less nucleophilic sulfonate leaving have so far not been described. By reaction of the optically active cyanohydrins (R)-1 as starting compounds with the sulfonyl halides and anhydrides 2, we have now been able to synthesize aliphatic and aromatic (R)-z-sulfonyloxynitriles (R)-3 free of racemization and in good yields. I/ c "'P,,, (R)-3With aliphatic cyanohydrins the tosylates and methaneand trifluoromethanesulfonates were synthesized in pure form. In the case of aromatic cyanohydrins, however, the preparation of mesylates is possible, but trifluoromethanesulfonates could only be synthesized and allowed to react in situ. These findings are consistent with data given in the literature on racemic cyanohydrin sulfonates, according to which the aliphatic compounds can be distilled without decomposition, whereas, e.g., the tosylate of mandelic nitrile already decomposes at room temperat~re. [~] So far, it has not been possible to develop a suitable method for the direct determination of the optical purity of the compounds (R)-3. No information about the enantiomeric excesses can be gleaned from the experimentally determined rotation values, which lie between + 20" and + 60°, because of a lack of data for comparison. That the sulfonylations of (R)-1 leading to (R)-3 proceed without racemization could be demonstrated by the reactions of the a-sulfonyloxynitriles (R)-3 with nucleophiles outlined in Scheme 1. According to Scheme 1, the cyanohydrin derivatives (3-4, a-( phthaloylamino)nitriles (3-5, a-azidonitriles (a-6, and aziridines (3-7 are readily accessible in optically active form from the compounds (R)-3.The reactions (b) and (c) have so far only been carried out with the aliphatic a-sulfonyloxynitriles (R)-3, the reactions (a) and (d) with both aliphatic as well as aromatic a-sulfonyloxynitriles (R)-3. Already at room temperature the reaction of (R)-3a with potassium acetate leads in very good yields to the cyanohydrin acetate (S)-4a, the enantiomeric purity of which was estimated by comparative investigations[6J to be 96.1 % ee. Since the (R)-1 a employed had an enantiomeric

Stereofacial Control in Asymmetric Cyanosilylation of Aldehydes Catalyzed by NovelS-Proline-Derived Titanium Complexes

“…The S-proline ligands (1-5) gave S product (up to 84% ee), whereas the C 2 -symmetric ligands (6,7) gave R product (up to 95% ee). Further investigations are planned to provide additional information with regard to the scope and the precise mechanism.…”

Dimeric & Polymeric Chiral Schiff Base Complexes and Supported BINOL Complexes as Potential Recyclable Catalysts in Asymmetric Kinetic Resolution and C–C Bond Formation Reactions

“…They can easily be prepared by the addition of cyanide to a carbonyl compound in the presence of a synthetic chiral catalyst or an enzyme (Scheme 2). The resulting cyanohydrins are readily transformed into a variety of compounds such as a-hydroxyacids [102], a-aminoacids [103][104][105][106][107][108][109][110][111][112], a-hydroxyaldehydes, a-hydroxyketones [113,114], b-aminoalcohols, among others [115][116][117][118][119][120][121][122][123][124][125][126][127]. Despite the immense synthetic potential offered by chiral cyanohydrins in the synthesis of bio-active molecules, it is surprising that intensive research on this topic has started relatively recently.…”

Asymmetric Cyanohydrin Synthesis Catalyzed by Mn(salen) Complex/Triphenylphosphine Oxide

“…The same authors [6e] used VO(salen) as the catalyst to give 6895% ee. Bu et al [10] modified the substituents of the benzene ring of the salen legand (tert-pentyl group) that is combined with Ti(OPr-i) 4 . The result indicated 8494% yield and 9297% ee.…”

“…These include a-hydroxy acids, [1,2] a-hydroxy aldehydes, [3] a-hydroxy ketones, [3] b-hydroxy amines, [2,3] and a-amino acid derivatives. [4] A number of catalysts for the asymmetric addition of cyanide to aldehydes [5] are known to include synthetic peptides and chiral transition metal complexes. Belokon,[6] Shibasaki, [7] Deng,[8] Hoveyda and Snapper, [9] and Bu [10] have made considerable contributions to development of the catalyst for the chiral silylcyanation.…”