Catalytic Asymmetric Synthesis of Cyclopentyl β‐Amino Esters by [3+2] Cycloaddition of Enecarbamates with Electrophilic Metalloenolcarbene Intermediates

Abstract

Chiral cyclopentyl b-amino esters are formed catalytically by [3+ +2] cycloaddition reactions of enecarbamates with electrophilic metalloenolcarbenes in high yield with up to 98 %e ea nd excellent diastereocontrol. Use of b-silylsubstituted enoldiazoacetates with ac hiral dirhodium catalyst and trans-b-arylvinylcarbamates are optimal for this transformation, which occurs with hydrogen-bond association between the vinylcarbamate and the intermediate metalloenolcarbene.R eductive conversion of the protected amino esters forms highly functionalizedc yclopentyl b-amino acids and 3aminocyclopentanones. Scheme 1. Bioactive cyclopentyl b-amino acids and derivatives. Supportinginformation and the ORCID identification number(s) for the author(s) of this article can be found under http://dx.doi.org/10. 1002/anie.201605438. Angewandte Chemie Communications Scheme 5. Reaction results of cis-2a and 7.D isfavoredtransition state of [3+ +2] cycloaddition of cis-b-phenylvinylcarbamate. Angewandte Chemie Communications

Generation and Rearrangement of N,O‐Dialkenylhydroxylamines for the Synthesis of 2‐Aminotetrahydrofurans

“…Cyclopentyl b-amino acid derivatives such as 9 are important scaffolds in avariety of biologically active molecules and this new route to highly substituted examples from 2-aminotetrahydro-furans 8 will help to broaden the accessibility of these privileged compounds. [20] Under longer reaction times, and in the absence of an electrophile,t he base-promoted tetrahydrofuran ring-opening and Mannich cyclization was also observed to occur with an elimination process to give cyclopentenones 10.T hese transformations were similarly diastereoselective as shown for 10 a and 10 b.T he conversion of 8i to 10 c also resulted in an increase in the diastereomeric ratio of the product in comparison to the starting material. [21] Cyclopentenones 10 have the opposite electronic substitution pattern to Nazarov rearrangement products and provide an opportunity to continue to expand structural diversity around this structure for synthetic applications.…”

Generation and Rearrangement of N,O‐Dialkenylhydroxylamines for the Synthesis of 2‐Aminotetrahydrofurans

“…The preferred conformation of this product was confirmed by Xray crystallography. [20] Under longer reaction times, and in the absence of an electrophile,t he base-promoted tetrahydrofuran ring-opening and Mannich cyclization was also observed to occur with an elimination process to give cyclopentenones 10.T hese transformations were similarly diastereoselective as shown for 10 a and 10 b.T he conversion of 8i to 10 c also resulted in an increase in the diastereomeric ratio of the product in comparison to the starting material. [19] In the absence of an electrophile,a na dventitious proton source gave 9e.…”