Formation of Optically Pure Cyclic Amines by Intramolecular Conjugate Displacement

Abstract

Intramolecular conjugate displacement (ICD) has been applied to the Morita-Baylis-Hillman adducts formed from (5S)-5-(l-menthyloxy)-2(5H)-furanone and aldehydes that carry a protected β- or γ-amino group. DIBAL-H reduction of the resulting ICD products releases optically pure six- or seven-membered cyclic amines having a stereogenic center α to nitrogen.

Isolation and structural characterization of stable carbamic–carbonic anhydrides: an experimental and computational study

“…Despite N-Boc derivatives can be obtained directly from the reaction between aliphatic primary and secondary amines with Boc 2 O, 9 the use of catalysts such as DMAP is widely employed as a standard protocol. 2,[10][11][12][13][14][15][16][17][18][19][20][21] In this sense, catalytic amounts of DMAP were used as a substitute for Et 3 N. After reacting for 5 min a new spot on TLC was found, with no changes in the TLC elution profile when the reaction time was extended up to 4 h.…”

Synthetic Studies on CP-225,917 and CP-263,114: Access to Advanced Tetracyclic Systems by Intramolecular Conjugate Displacement and [2,3]-Wittig Rearrangement

“…The next step was a crucial one as it set the stage for using the method of intramolecular conjugate displacement to generate the 9-membered ring that is characteristic of both CP-225,917 and CP-263,114. A critical requirement is that the stereochemistry at C(10) of 6.4 should be as shown.…”

“…We describe here our own model studies that have led to the preparation of 3 and 4 . The methods we have used illustrate the power of intramolecular conjugate displacement for making complex structures and the value of the [2,3]-Wittig rearrangement to install a hydroxymethyl group where other methods failed. We have also found a new variant of the [2,3]-Wittig rearrangement.…”

Computations Reveal That Electron-Withdrawing Leaving Groups Facilitate Intramolecular Conjugate Displacement Reactions by Negative Hyperconjugation

“…The reaction is base-promoted and requires a nucleophile, Michael acceptor, and leaving group. The ICD process works with carbon and nitrogen nucleophiles. , ICD reactions may also be involved in biosynthetic pathways, an example with oxygen as the nucleophile is in the biosynthesis of rossinone B …”