Dynamic Behavior of Chiral Sulfonimidoyl-Substituted Allyl and Alkyl (Dimethylamino)titanium(IV) Complexes:  Metallotropic Shift, Reversible β-Hydride Elimination/Reinsertion, and ab Initio Calculations of Allyl and Alkyl Aminosulfoxonium Ylides

Abstract

Variable-temperature (1)H and (13)C NMR spectroscopy of the sulfonimidoyl-substituted allyltitanium(IV) complexes E-1a-c and Z-1a-c, which carry diethylamino groups at the Ti atom, revealed a fast 1,3-C,N-shift of the Ti atom, leading to an equilibrium between the epimeric Calpha-titanium allyl complexes A and C and the N-titanium allyl aminosulfoxonium ylide B. Based on these findings a model for the reactions of E-1a-c and Z-1a-c with aldehydes is proposed, which features regio- and diastereoselective reactions of the N-titanium ylide B at the alpha-position and the Calpha-titanium complex A at the gamma-position. Model ab initio calculations of the methylene and allyl (dimethylamino)sulfoxonium ylides 10 and 14, respectively, revealed short Calpha-S bonds, a stabilization by both electrostatic interaction and negative hyperconjugation, and a low Calpha-S rotational barrier. The ylides preferentially adopt Calpha-S and Calpha-N conformations in which the lone pair orbital at the Calpha atom is periplanar to the S=O bond and that at the N atom periplanar to the Calpha-Ph bond. Variable-temperature NMR spectroscopy of the sulfonimidoyl-substituted alkyltitanium(IV) complex 16, which carries diethylamino groups at the Ti atom, revealed a dynamic behavior leading to a complete topomerization of all four methylene hydrogens of the Calpha-ethyl groups. Two fast processes are held responsible for the topomerization of the hydrogens of 16. The first one is a reversible intramolecular beta-hydride elimination/alkene-Ti-H insertion with the intermediate formation of a complex between (Et(2)N)TiH and a 1-alkenyl sulfoximine, and the second one consists of a reversible 1,3-C,N-shift of the Ti atom in combination with a Calpha-S bond rotation. Interestingly, the room-temperature NMR spectra of the corresponding sulfonimidoyl-substituted alkyltitanium(IV) complex 17, which carries isopropoxy groups at the Ti atom, give no indication of a similar dynamic behavior of this complex.

Functionalized Chiral Vinyl Aminosulfoxonium Salts: Asymmetric Synthesis and Application to the Synthesis of Enantiopure Unsaturated Prolines, β,γ-Dehydro Amino Acids, and Cyclopentanoid Keto Aminosulfoxonium Ylides

“…Similarly the titanium complexes 28a − d react with aldehydes with high regio- and diastereoselectivities at the γ-position to afford the corresponding anti -configured homoallyl alcohols having, however, a Z -configured vinylic sulfoximine . In contrast it was found that the mono(allyl)titanium complexes 30a − d , which are also readily available from 27a − d through lithiation and titanation with ClTi(NEt 2 ) 3 , react with aldehydes with high regio- and diastereoselectivities at the α-position to furnish the corresponding allyl sulfoximines. ,, It was thus of interest to study the reactions of 30a − d with 4 to see whether the mono(allyl)titanium complexes show a similar reactivity toward the imino ester.

6 Structure of the functionalized cyclic vinyl sulfoximine 31c in the crystal.

9 Stereo-Complementary Aminoalkylation of Cyclic Sulfonimidoyl-Substituted Allyl Titanium Complexes

…”

“…A NMR spectroscopic investigation of the structure of the acyclic mono(allyl)titanium complexes 32a and 32b had revealed a low configurational stability of the Cα atom and a fast Cα,N-shift of the titanium atom leading to the formation of an equilibrium mixture of complexes 32A − C in ratios of 84:13:3 and 86:12:2, respectively (Scheme ). , The formation of the syn -configured diastereomers 33 and 5 in the reaction of 32 with 4 can thus be rationalized, on the assumption of the operation of the Curtin-Hammett principle, by proposing a stereo- and regioselective reaction of the ( S C α )-configured complex 32A with 4 through a six-membered cyclic transition state of type TS- E - 33 giving 33 and of the ( R C α )-configured complex 32C with 4 through TS- E - 5 leading to 5 . The preferential formation of the E , R C α , S C β -configured vinyl sulfoximine E - 33 points to a higher reactivity of the ( S C α )-configured complex 32A .…”

“…Ylide Al- 54 and the model ylide XXIII adopt a C1−S conformation in which the lone pair at C1 and the S−N bond are approximately in a syn/planar position. According to an ab initio calculation of (dimethylamino)phenylsulfoxonium methylide this conformation allows for a stabilizing n C −σ* SN hyperconjugative interaction (vide supra) . Furthermore the methylene ylide adopts, according to the calculations, S−N and C−S conformations in which the lone pairs at the C atom and N atom are in an almost orthogonal position.…”

“…Furthermore the methylene ylide adopts, according to the calculations, S−N and C−S conformations in which the lone pairs at the C atom and N atom are in an almost orthogonal position. Thereby, a destabilizing interaction between both lone pairs is avoided that results when they are in a planar position . Ylide Al- 54 and the model ylide XXIII adopt similar S−N and C−S conformations.…”

Functionalized Chiral Vinyl Aminosulfoxonium Salts: Asymmetric Synthesis and Application to the Synthesis of Enantiopure Unsaturated Prolines, β,γ-Dehydro Amino Acids, and Cyclopentanoid Keto Aminosulfoxonium Ylides

“…Similarly the titanium complexes 28a − d react with aldehydes with high regio- and diastereoselectivities at the γ-position to afford the corresponding anti -configured homoallyl alcohols having, however, a Z -configured vinylic sulfoximine . In contrast it was found that the mono(allyl)titanium complexes 30a − d , which are also readily available from 27a − d through lithiation and titanation with ClTi(NEt 2 ) 3 , react with aldehydes with high regio- and diastereoselectivities at the α-position to furnish the corresponding allyl sulfoximines. ,, It was thus of interest to study the reactions of 30a − d with 4 to see whether the mono(allyl)titanium complexes show a similar reactivity toward the imino ester.

6 Structure of the functionalized cyclic vinyl sulfoximine 31c in the crystal.

9 Stereo-Complementary Aminoalkylation of Cyclic Sulfonimidoyl-Substituted Allyl Titanium Complexes

…”

“…A NMR spectroscopic investigation of the structure of the acyclic mono(allyl)titanium complexes 32a and 32b had revealed a low configurational stability of the Cα atom and a fast Cα,N-shift of the titanium atom leading to the formation of an equilibrium mixture of complexes 32A − C in ratios of 84:13:3 and 86:12:2, respectively (Scheme ). , The formation of the syn -configured diastereomers 33 and 5 in the reaction of 32 with 4 can thus be rationalized, on the assumption of the operation of the Curtin-Hammett principle, by proposing a stereo- and regioselective reaction of the ( S C α )-configured complex 32A with 4 through a six-membered cyclic transition state of type TS- E - 33 giving 33 and of the ( R C α )-configured complex 32C with 4 through TS- E - 5 leading to 5 . The preferential formation of the E , R C α , S C β -configured vinyl sulfoximine E - 33 points to a higher reactivity of the ( S C α )-configured complex 32A .…”

“…Ylide Al- 54 and the model ylide XXIII adopt a C1−S conformation in which the lone pair at C1 and the S−N bond are approximately in a syn/planar position. According to an ab initio calculation of (dimethylamino)phenylsulfoxonium methylide this conformation allows for a stabilizing n C −σ* SN hyperconjugative interaction (vide supra) . Furthermore the methylene ylide adopts, according to the calculations, S−N and C−S conformations in which the lone pairs at the C atom and N atom are in an almost orthogonal position.…”

“…Furthermore the methylene ylide adopts, according to the calculations, S−N and C−S conformations in which the lone pairs at the C atom and N atom are in an almost orthogonal position. Thereby, a destabilizing interaction between both lone pairs is avoided that results when they are in a planar position . Ylide Al- 54 and the model ylide XXIII adopt similar S−N and C−S conformations.…”

Asymmetric Synthesis of Highly Substituted Azapolycyclic Compounds via 2-Alkenyl Sulfoximines: Potential Scaffolds for Peptide Mimetics

“…In 1994 we discovered that titanated open-chain 2-alkenyl sulfoximines 3 , derived from cyclic sulfonimidates 1 , are highly stereoselective allyl transfer reagents (Scheme ) . Shortly after that, Gais et al introduced N -methyl substituted 2-alkenyl sulfoximines which he elaborated into useful synthetic tools for asymmetric synthesis 1 General Outline of the Method; S i j Denotes the Chiral Sulfonimidoyl Unit as Specified in Chart …”

Functionalized Chiral Vinyl Aminosulfoxonium Salts: Asymmetric Synthesis and Application to the Synthesis of Enantiopure Unsaturated Prolines, β,γ-Dehydro Amino Acids, and Cyclopentanoid Keto Aminosulfoxonium Ylides

“…Similarly the titanium complexes 28a − d react with aldehydes with high regio- and diastereoselectivities at the γ-position to afford the corresponding anti -configured homoallyl alcohols having, however, a Z -configured vinylic sulfoximine . In contrast it was found that the mono(allyl)titanium complexes 30a − d , which are also readily available from 27a − d through lithiation and titanation with ClTi(NEt 2 ) 3 , react with aldehydes with high regio- and diastereoselectivities at the α-position to furnish the corresponding allyl sulfoximines. ,, It was thus of interest to study the reactions of 30a − d with 4 to see whether the mono(allyl)titanium complexes show a similar reactivity toward the imino ester.

6 Structure of the functionalized cyclic vinyl sulfoximine 31c in the crystal.

9 Stereo-Complementary Aminoalkylation of Cyclic Sulfonimidoyl-Substituted Allyl Titanium Complexes

…”

“…A NMR spectroscopic investigation of the structure of the acyclic mono(allyl)titanium complexes 32a and 32b had revealed a low configurational stability of the Cα atom and a fast Cα,N-shift of the titanium atom leading to the formation of an equilibrium mixture of complexes 32A − C in ratios of 84:13:3 and 86:12:2, respectively (Scheme ). , The formation of the syn -configured diastereomers 33 and 5 in the reaction of 32 with 4 can thus be rationalized, on the assumption of the operation of the Curtin-Hammett principle, by proposing a stereo- and regioselective reaction of the ( S C α )-configured complex 32A with 4 through a six-membered cyclic transition state of type TS- E - 33 giving 33 and of the ( R C α )-configured complex 32C with 4 through TS- E - 5 leading to 5 . The preferential formation of the E , R C α , S C β -configured vinyl sulfoximine E - 33 points to a higher reactivity of the ( S C α )-configured complex 32A .…”

“…Ylide Al- 54 and the model ylide XXIII adopt a C1−S conformation in which the lone pair at C1 and the S−N bond are approximately in a syn/planar position. According to an ab initio calculation of (dimethylamino)phenylsulfoxonium methylide this conformation allows for a stabilizing n C −σ* SN hyperconjugative interaction (vide supra) . Furthermore the methylene ylide adopts, according to the calculations, S−N and C−S conformations in which the lone pairs at the C atom and N atom are in an almost orthogonal position.…”

“…Furthermore the methylene ylide adopts, according to the calculations, S−N and C−S conformations in which the lone pairs at the C atom and N atom are in an almost orthogonal position. Thereby, a destabilizing interaction between both lone pairs is avoided that results when they are in a planar position . Ylide Al- 54 and the model ylide XXIII adopt similar S−N and C−S conformations.…”

Asymmetric Synthesis of Highly Substituted Azapolycyclic Compounds via 2-Alkenyl Sulfoximines: Potential Scaffolds for Peptide Mimetics

“…In 1994 we discovered that titanated open-chain 2-alkenyl sulfoximines 3 , derived from cyclic sulfonimidates 1 , are highly stereoselective allyl transfer reagents (Scheme ) . Shortly after that, Gais et al introduced N -methyl substituted 2-alkenyl sulfoximines which he elaborated into useful synthetic tools for asymmetric synthesis 1 General Outline of the Method; S i j Denotes the Chiral Sulfonimidoyl Unit as Specified in Chart …”

Functionalized Chiral Vinyl Aminosulfoxonium Salts: Asymmetric Synthesis and Application to the Synthesis of Enantiopure Unsaturated Prolines, β,γ-Dehydro Amino Acids, and Cyclopentanoid Keto Aminosulfoxonium Ylides

“…Similarly the titanium complexes 28a − d react with aldehydes with high regio- and diastereoselectivities at the γ-position to afford the corresponding anti -configured homoallyl alcohols having, however, a Z -configured vinylic sulfoximine . In contrast it was found that the mono(allyl)titanium complexes 30a − d , which are also readily available from 27a − d through lithiation and titanation with ClTi(NEt 2 ) 3 , react with aldehydes with high regio- and diastereoselectivities at the α-position to furnish the corresponding allyl sulfoximines. ,, It was thus of interest to study the reactions of 30a − d with 4 to see whether the mono(allyl)titanium complexes show a similar reactivity toward the imino ester.

6 Structure of the functionalized cyclic vinyl sulfoximine 31c in the crystal.

9 Stereo-Complementary Aminoalkylation of Cyclic Sulfonimidoyl-Substituted Allyl Titanium Complexes

…”

“…A NMR spectroscopic investigation of the structure of the acyclic mono(allyl)titanium complexes 32a and 32b had revealed a low configurational stability of the Cα atom and a fast Cα,N-shift of the titanium atom leading to the formation of an equilibrium mixture of complexes 32A − C in ratios of 84:13:3 and 86:12:2, respectively (Scheme ). , The formation of the syn -configured diastereomers 33 and 5 in the reaction of 32 with 4 can thus be rationalized, on the assumption of the operation of the Curtin-Hammett principle, by proposing a stereo- and regioselective reaction of the ( S C α )-configured complex 32A with 4 through a six-membered cyclic transition state of type TS- E - 33 giving 33 and of the ( R C α )-configured complex 32C with 4 through TS- E - 5 leading to 5 . The preferential formation of the E , R C α , S C β -configured vinyl sulfoximine E - 33 points to a higher reactivity of the ( S C α )-configured complex 32A .…”

“…Ylide Al- 54 and the model ylide XXIII adopt a C1−S conformation in which the lone pair at C1 and the S−N bond are approximately in a syn/planar position. According to an ab initio calculation of (dimethylamino)phenylsulfoxonium methylide this conformation allows for a stabilizing n C −σ* SN hyperconjugative interaction (vide supra) . Furthermore the methylene ylide adopts, according to the calculations, S−N and C−S conformations in which the lone pairs at the C atom and N atom are in an almost orthogonal position.…”

“…Furthermore the methylene ylide adopts, according to the calculations, S−N and C−S conformations in which the lone pairs at the C atom and N atom are in an almost orthogonal position. Thereby, a destabilizing interaction between both lone pairs is avoided that results when they are in a planar position . Ylide Al- 54 and the model ylide XXIII adopt similar S−N and C−S conformations.…”

Asymmetric Synthesis of Highly Substituted Azapolycyclic Compounds via 2-Alkenyl Sulfoximines: Potential Scaffolds for Peptide Mimetics

“…In 1994 we discovered that titanated open-chain 2-alkenyl sulfoximines 3 , derived from cyclic sulfonimidates 1 , are highly stereoselective allyl transfer reagents (Scheme ) . Shortly after that, Gais et al introduced N -methyl substituted 2-alkenyl sulfoximines which he elaborated into useful synthetic tools for asymmetric synthesis 1 General Outline of the Method; S i j Denotes the Chiral Sulfonimidoyl Unit as Specified in Chart …”