Diastereoselective Addition of α-Metalated Sulfoxides to Imines Revisited: Mechanism, Computational Studies, and the Effect of External Chiral Ligands

Some new results on asymmetric synthesis via the addition of α-metalated methyl tolyl sulfoxides to imines are presented. Good diastereoselectivity (up to >98% d.e. for product 3g ) can be obtained under conditions of kinetic control (short reaction time, low temperature). The transition state (a six-membered "flat chair") was probed by quantum mechanical calculations, which underpinned the idea of using external chiral ligands to enhance the diastereoselectivity of otherwise moderately selective reactions. In this way, the diastereomeric ratio of the product 3a could be raised from (84:16) to (>99:1) by use of a readily available C 2 -symmetric bis(sulfonamide) ligand.

[1]  P. Norrby,et al.  Computational investigation of the role of fluoride in Tamao oxidations. , 2002, Chemistry.

[2]  G. Gelli,et al.  Addition of 1,3‐Benzoxathiole 3‐Oxide Anion to Azomethines under Varying Reaction Conditions , 2002 .

[3]  Malcolm B. Gillies,et al.  Quantum Chemical Calculations on the Peterson Olefination with α-Silyl Ester Enolates , 2002 .

[4]  A. Volonterio,et al.  The ‘non-oxidative’ chloro-Pummerer reaction: a highly stereoselective entry to β-chloro amines and aziridines , 2001 .

[5]  S. Bhat,et al.  Asymmetric synthesis of β-amino acids through application of chiral sulfoxide , 2001 .

[6]  S. V. Meille,et al.  On the Additions of Lithium Methyl p-Tolyl Sulfoxide to N-(PMP)Arylaldimines , 2001, Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry.

[7]  M. Naimi-Jamal,et al.  The LiClO4-Mediated Synthesis of β-(Dialkylamino) Sulfoxides and β-(Dialkylamino) Sulfones by Addition of α-Lithiated Salts of Sulfoxides and Sulfones to Aldehydes and (Trimethylsilyl)dialkylamines , 2000 .

[8]  S. V. Meille,et al.  Asymmetric synthesis of α-arylglycinols via additions of lithium methyl p-tolyl sulfoxide to N-(PMP)arylaldimines followed by “non oxidative” Pummerer reaction , 1999 .

[9]  C. Pettinari,et al.  Synthesis and Structural Investigations of Novel Palladium(II) and Rhodium(I) Complexes Containing Chiral Ligands with a Stereogenic Sulfur Donor, Such As β-Amino Sulfoxides and C2-Symmetric Bis-Sulfoxides1 , 1999 .

[10]  R. Bloch.  Additions of Organometallic Reagents to C=N Bonds: Reactivity and Selectivity , 1998 .

[11]  T. Tsuda,et al.  The reaction of nitrones with (R)-(+)-methyl p-tolyl sulfoxide anion; asymmetric synthesis of optically active secondary amines , 1993 .

[12]  A. J. Walker.  Asymmetric carbon-carbon bond formation using sulfoxide-stabilised carbanions , 1992 .

[13]  G. Boche,et al.  Chiral sulfur compounds. 7. Stereoselective reactions of lithium and zinc tert-butyl phenylmethyl sulfoxide with carbonyl compounds and imines , 1989 .

[14]  G. Solladié.  Recent results in the field of asymmetric synthesis using chiral sulfoxides , 1988 .

[15]  H. Flack,et al.  On enantiomorph‐polarity estimation , 1983 .

[16]  T. Harris,et al.  Condensations at the 6 position of the methyl ester and the dimethylamide of 3,5-dioxohexanoic acid via 2,4,6-trianions , 1981 .

[17]  S. Ueda.  Replacement of methoxyl group on the grignard reaction of N-(o-methoxybenzylidene)aniline. , 1979 .

[18]  K. Balachandran,et al.  Oxidation by metal oxides. IV. Oxidation of organic compounds using nickel peroxide , 1968 .

[19]  J. Montgomery,et al.  Kinetics of the Catalytic Hydrogenation of Certain Schiff Bases1 , 1953 .

[20]  S. Pyne,et al.  Diastereoselective kinetically and thermodynamically controlled additions of (R)-(+)-methyl p-tolyl sulphoxide anion to imines (tolyl = C6H4Me) , 1989 .

[21]  H. Kagan,et al.  Asymmetric additions of α-sulfoxide carbanion on imines , 1988 .

[22]  C. J. Lovely,et al.  An efficient method for the preparation of N-phosphinoyl and N-sulphonyl imines directly from aromatic aldehydes , 1988 .

[23]  R. Grigg,et al.  The Reduction of Aldimines by Hydrogen Transfer from Propan-2-ol Catalysed by Rhodium Complexes , 1981 .

[24]  S. Iriuchijima,et al.  Asymmetric synthesis using α-sulfinylcarbanions. I. Synthesis of optically active alcohols , 1972 .