Scope and mechanism of formal S(N)2' substitution reactions of a monomeric imidozirconium complex with allylic electrophiles.
The zirconium imido complex Cp2(THF)Zr=NSi(t-Bu)Me2 (1) reacts with allylic ethers, chlorides, and bromides to give exclusively the products of the SN2' reaction; i.e., attack at the allylic position remote from the leaving group with migration of the double bond. The primary amine products can be isolated in excellent yields, after in situ Cbz protection, in the presence of variety of functional groups. Good diastereoselectivity and complete stereoselectivity allowed the formation of enantioenriched allylic amines from enantioenriched allylic ethers. Regiospecific substitution with 1 has also been achieved with allylic fluorides, which are notoriously poor substrates in other substitution reactions. On the basis of rate and kinetic isotope effect studies, we propose a general mechanism for the allylic substitution reactions with 1 which involves dissociation of THF and binding of the substrate, followed by the substitution step. In a DFT study of the substitution reaction, we identified a six-membered closed transition state for the substitution step and other relevant stationary points along the reaction coordinate. This study shows that the substitution reaction can be described as a concerted asynchronous [3,3]-sigmatropic rearrangement. This detailed knowledge of the reaction mechanism provides a rationale for the origins of the observed regio-, diastereo-, and stereoselectivity and of the unusual reactivity profile observed in the reaction.
Lalic
Gojko
G
Department of Chemistry, University of California, Berkeley, California 94720, USA.
Krinsky
Jamin L
JL
Bergman
Robert G
RG
D000588:Amines / Q000737:chemistry; D004987:Ethers / Q000737:chemistry; D006846:Hydrocarbons, Halogenated / Q000737:chemistry; D007094:Imides / Q000737:chemistry*; D008956:Models, Chemical; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism; D015040:Zirconium / Q000737:chemistry*
D000588:Amines; D004987:Ethers; D006846:Hydrocarbons, Halogenated; D007094:Imides; D009942:Organometallic Compounds; D015040:Zirconium