N-Methylsulfonimidoyl-Substituted (2-Alkenyl)titanium Complexes: Application to the Synthesis of β- and δ-Sulfonimidoyl-Substituted Chiral Homoallylic Alcohols, X-ray Crystal Structure Analysis, and Fluxional Behavior

Abstract

Enantiopure acyclic (E)‐ and (Z)‐configured allylic sulfoximines have been synthesized from N,S‐dimethyl‐S‐phenylsulfoximine and aldehydes by the addition− elimination−isomerization route through the intermediate generation of the corresponding (E)‐configured vinylic sulfoximines. Isomerization of the vinylic sulfoximines with DBU preferentially afforded the corresponding (Z)‐configured allylic sulfoximines, which were subsequently isomerized by DBU to preferentially yield the (E)‐isomers. Titanation of lithiated (E)‐configured allylic sulfoximines with ClTi(OiPr)3 furnished the corresponding bis(2‐alkenyl)diisopropyloxytitanium(IV) complexes, which reacted with aldehydes in the presence of ClTi(OiPr)3 with high regio‐ and diastereoselectivities at the γ‐position to give the corresponding (Z)‐anti‐configured δ‐N‐methylsulfonimidoyl‐substituted homoallylic alcohols in good yields. In the absence of ClTi(OiPr)3 at low temperatures, only one allylic moiety of the bis(alkenyl)diisopropyloxytitanium complex is transferred to the aldehyde. In this way, a cyclic lithiated allylic sulfoximine has been converted with high regio‐ and diastereoselectivity to the corresponding homoallylic alcohols bearing a vinylic sulfonimidoyl group. Titanation of lithiated (E)‐ and (Z)‐configured allylic sulfoximines with ClTi(NEt2)3 afforded the corresponding mono(2‐alkenyl)tris(diethylamino)titanium(IV) complexes, which reacted with aldehydes with moderate to high regioselectivities and high diastereoselectivities preferentially at the α‐position to give the corresponding syn‐configured β‐N‐methylsulfonimidoyl‐substituted homoallylic alcohols along with the (Z)‐anti‐configured δ‐N‐methylsulfonimidoyl‐substituted homoallylic alcohols in good yields. In this way, the cyclic lithiated allylic sulfoximine was converted with high regio‐ and diastereoselectivity to the corresponding isomeric homoallylic alcohols bearing an allylic sulfonimidoyl group. In the case of mono(alkenyl)tris(diethylamino)titanium(IV) complexes, the regioselectivity of their reactions with aldehydes has been found to depend on the size of the substituent at the CC double bond and the aldehyde, as well as on the configuration of the double bond. Reaction of racemic lithiated N‐methyl‐S‐(3,3‐diphenyl‐2‐propenyl)‐S‐phenylsulfoximine with ClTi(OiPr)3 afforded the corresponding bis(alkenyl)diisopropyloxytitanium(IV) complex. X‐ray structure analysis revealed a distorted octahedral cis,cis,cis‐configured bis(2‐alkenyl)diisopropyloxytitanium(IV) complex, in which the allylic moieties are coordinated in a bidentate fashion through C‐α and the N atom to the Ti atom, both having the relative configuration RSSC. In solution, the titanium complex shows fluxional behavior, which is characterized by topomerization of the isopropyloxy groups and allylic moieties. The exchange of the latter occurs with retention of the configuration at C‐α.

Highly Selective Addition of Chiral, Sulfonimidoyl Substituted Bis(allyl)titanium Complexes to N-Sulfonyl α-Imino Esters: Asymmetric Synthesis of γ,δ-Unsaturated α-Amino Acids Bearing a Chiral, Electron-Withdrawing Nucleofuge at the δ-Position

“…However, under these conditions, only one allylic sulfoximine moiety of the bis(allyl)titanium complex 5a was utilized in the reaction with the 9a as revealed by a recovery of approximately 50% of the starting allylic sulfoximine 12a . A similar observation had been made previously in the case of the reaction of complexes 5a − d with aldehydes 12c. In this case, treatment of 5a − d before addition of the aldehyde with 1 equiv of ClTi(O i Pr) 3 ensured a transfer of both allylic sulfoximine moieties with high regio- and diastereoselectivity.…”

Highly Selective Addition of Chiral, Sulfonimidoyl Substituted Bis(allyl)titanium Complexes to N-Sulfonyl α-Imino Esters: Asymmetric Synthesis of γ,δ-Unsaturated α-Amino Acids Bearing a Chiral, Electron-Withdrawing Nucleofuge at the δ-Position

“…However, under these conditions, only one allylic sulfoximine moiety of the bis(allyl)titanium complex 5a was utilized in the reaction with the 9a as revealed by a recovery of approximately 50% of the starting allylic sulfoximine 12a . A similar observation had been made previously in the case of the reaction of complexes 5a − d with aldehydes 12c. In this case, treatment of 5a − d before addition of the aldehyde with 1 equiv of ClTi(O i Pr) 3 ensured a transfer of both allylic sulfoximine moieties with high regio- and diastereoselectivity.…”

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

“…For example, if one would propose that two of the three equilibrium species adopt the structure F or G rather than A , B , and C , chemical shifts of 3.12−3.72 and of 4.94−5.22 would have to be assigned to 1-H and 3-H, respectively, of F or G . This does, however, not concur with the NMR data of the known allyltitanium(IV) complexes including those of complexes 6 − 8 . 1f,, A comparison of the 13 C NMR data of the equilibrium species E - A and E - B with those of the 1-alkenyl sulfoximines E - 11 and E - 12 also shows, in agreement with the 1 H NMR data (vide supra), that the alternative structures F and G for the equilibrium species of complexes E - 1a − c can be excluded. In particular δ values of 55.46−61.08 and 1 J (C,H) values of 137−141 Hz for C-1 would be incompatible with structures F and G .…”

Analysis of Interactions between the Epidermal Growth Factor Receptor and Soluble Ligands on the Basis of Single‐Molecule Diffusivity in the Membrane of Living Cells

“…It is interesting to note that bis(1‐sulfonimidoylpropenyl)titanium 10a adopts a similar structure in the crystal (Figure 4) as bis(1‐sulfonylalkyl)titaniums 6a , 6b and 9a 6. Whereas 10a has the cis , cis , cis ‐configuration, 6a , 6b and 9a have the cis , cis , trans ‐configuration.…”

Highly Selective Addition of Chiral, Sulfonimidoyl Substituted Bis(allyl)titanium Complexes to N-Sulfonyl α-Imino Esters: Asymmetric Synthesis of γ,δ-Unsaturated α-Amino Acids Bearing a Chiral, Electron-Withdrawing Nucleofuge at the δ-Position

“…However, under these conditions, only one allylic sulfoximine moiety of the bis(allyl)titanium complex 5a was utilized in the reaction with the 9a as revealed by a recovery of approximately 50% of the starting allylic sulfoximine 12a . A similar observation had been made previously in the case of the reaction of complexes 5a − d with aldehydes 12c. In this case, treatment of 5a − d before addition of the aldehyde with 1 equiv of ClTi(O i Pr) 3 ensured a transfer of both allylic sulfoximine moieties with high regio- and diastereoselectivity.…”

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

“…For example, if one would propose that two of the three equilibrium species adopt the structure F or G rather than A , B , and C , chemical shifts of 3.12−3.72 and of 4.94−5.22 would have to be assigned to 1-H and 3-H, respectively, of F or G . This does, however, not concur with the NMR data of the known allyltitanium(IV) complexes including those of complexes 6 − 8 . 1f,, A comparison of the 13 C NMR data of the equilibrium species E - A and E - B with those of the 1-alkenyl sulfoximines E - 11 and E - 12 also shows, in agreement with the 1 H NMR data (vide supra), that the alternative structures F and G for the equilibrium species of complexes E - 1a − c can be excluded. In particular δ values of 55.46−61.08 and 1 J (C,H) values of 137−141 Hz for C-1 would be incompatible with structures F and G .…”

Analysis of Interactions between the Epidermal Growth Factor Receptor and Soluble Ligands on the Basis of Single‐Molecule Diffusivity in the Membrane of Living Cells

“…It is interesting to note that bis(1‐sulfonimidoylpropenyl)titanium 10a adopts a similar structure in the crystal (Figure 4) as bis(1‐sulfonylalkyl)titaniums 6a , 6b and 9a 6. Whereas 10a has the cis , cis , cis ‐configuration, 6a , 6b and 9a have the cis , cis , trans ‐configuration.…”

Highly Selective Addition of Chiral, Sulfonimidoyl Substituted Bis(allyl)titanium Complexes to N-Sulfonyl α-Imino Esters: Asymmetric Synthesis of γ,δ-Unsaturated α-Amino Acids Bearing a Chiral, Electron-Withdrawing Nucleofuge at the δ-Position

“…However, under these conditions, only one allylic sulfoximine moiety of the bis(allyl)titanium complex 5a was utilized in the reaction with the 9a as revealed by a recovery of approximately 50% of the starting allylic sulfoximine 12a . A similar observation had been made previously in the case of the reaction of complexes 5a − d with aldehydes 12c. In this case, treatment of 5a − d before addition of the aldehyde with 1 equiv of ClTi(O i Pr) 3 ensured a transfer of both allylic sulfoximine moieties with high regio- and diastereoselectivity.…”

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

“…For example, if one would propose that two of the three equilibrium species adopt the structure F or G rather than A , B , and C , chemical shifts of 3.12−3.72 and of 4.94−5.22 would have to be assigned to 1-H and 3-H, respectively, of F or G . This does, however, not concur with the NMR data of the known allyltitanium(IV) complexes including those of complexes 6 − 8 . 1f,, A comparison of the 13 C NMR data of the equilibrium species E - A and E - B with those of the 1-alkenyl sulfoximines E - 11 and E - 12 also shows, in agreement with the 1 H NMR data (vide supra), that the alternative structures F and G for the equilibrium species of complexes E - 1a − c can be excluded. In particular δ values of 55.46−61.08 and 1 J (C,H) values of 137−141 Hz for C-1 would be incompatible with structures F and G .…”

Analysis of Interactions between the Epidermal Growth Factor Receptor and Soluble Ligands on the Basis of Single‐Molecule Diffusivity in the Membrane of Living Cells

“…It is interesting to note that bis(1‐sulfonimidoylpropenyl)titanium 10a adopts a similar structure in the crystal (Figure 4) as bis(1‐sulfonylalkyl)titaniums 6a , 6b and 9a 6. Whereas 10a has the cis , cis , cis ‐configuration, 6a , 6b and 9a have the cis , cis , trans ‐configuration.…”