SN1-like Reactions of Bicyclic α-Amino Ethers with Sulfur, Nitrogen, and Carbon Nucleophiles. Synthesis of 1-Azabicyclo[3.2.2]nonanes Functionalized at Carbon C2 and C6 with Complete Stereocontrol
Abstract:[reaction: see text] In the presence of nucleophiles, Lewis acid mediated cleavage of alpha-amino ethers derived from quincorine and quincoridine affords a variety of C2-substituted and C6-vinylated 1-azabicyclo[3.2.2]nonanes. These are enantiopure and are formed in S(N)1-like reactions with complete stereocontrol. There is no leakage into 2-Nu en route to product 1-Nu or vice versa. Me(3)SiCN provides new Strecker-type alpha-amino nitriles. In the presence of TTMPP-BF(3).OEt(2), the ketene acetal Me(2)C=C(OMe… Show more
“…409–412,102 Although several bridgehead imines and iminium ions have been reported, 413–419 only a few of these compounds bear nitrogen atom at the bridgehead position in a bicyclic system. 420–424,353,354 …”
Section: Synthesis Of Bridged Lactams With Complex Ring Systems Anmentioning
confidence: 99%
“…424 A wide range of carbon, nitrogen and sufur nucleophiles was used to capture bridged iminium ions 373 and 376 with complete diastereoselectivity.…”
Section: Synthesis Of Bridged Lactams With Complex Ring Systems Anmentioning
CONTENTS 1. Introduction 5702 2. General Properties of Bridged Lactams 5703 2.1. Distortion Parameters of Bridged Lactams 5703 2.2. Bond Lengths of Bridged Lactams 5703 2.3. Spectroscopic Properties of Bridged Lactams 5703 2.4. Analogy of Bridged Lactams to Bridgehead Olefins 5704 2.5. Chemical and Biological Significance of Distorted Amides 5704 3. Synthesis of Historically Important Bridged Lactams 5704 3.1. Quinuclidone Derivatives 5704 3.2. Adamantanone Derivatives 5707 4. Synthesis of Bridged Lactams with the N−(CO) Bond on a Two-Carbon or Larger Bridge, ([m. (≥2).n] Type) 5708 4.1. Condensation Reactions Forming the N− C(O) Bond 5708 4.2. Heck Reactions 5711 4.3. Diels−Alder Reactions 5712 4.4. Carbene Insertion Reactions 5713 4.5. Reactions via Radical Intermediates 5714 4.6. Miscellaneous Examples 5714 5. Synthesis of Bridged Lactams with the N−(CO) Bond on a One-Carbon Bridge, ([m.1.n] Type) 5715 5.1. Carbene Insertion Reactions 5715 5.2. Schmidt Reactions 5716 5.3.
“…409–412,102 Although several bridgehead imines and iminium ions have been reported, 413–419 only a few of these compounds bear nitrogen atom at the bridgehead position in a bicyclic system. 420–424,353,354 …”
Section: Synthesis Of Bridged Lactams With Complex Ring Systems Anmentioning
confidence: 99%
“…424 A wide range of carbon, nitrogen and sufur nucleophiles was used to capture bridged iminium ions 373 and 376 with complete diastereoselectivity.…”
Section: Synthesis Of Bridged Lactams With Complex Ring Systems Anmentioning
CONTENTS 1. Introduction 5702 2. General Properties of Bridged Lactams 5703 2.1. Distortion Parameters of Bridged Lactams 5703 2.2. Bond Lengths of Bridged Lactams 5703 2.3. Spectroscopic Properties of Bridged Lactams 5703 2.4. Analogy of Bridged Lactams to Bridgehead Olefins 5704 2.5. Chemical and Biological Significance of Distorted Amides 5704 3. Synthesis of Historically Important Bridged Lactams 5704 3.1. Quinuclidone Derivatives 5704 3.2. Adamantanone Derivatives 5707 4. Synthesis of Bridged Lactams with the N−(CO) Bond on a Two-Carbon or Larger Bridge, ([m. (≥2).n] Type) 5708 4.1. Condensation Reactions Forming the N− C(O) Bond 5708 4.2. Heck Reactions 5711 4.3. Diels−Alder Reactions 5712 4.4. Carbene Insertion Reactions 5713 4.5. Reactions via Radical Intermediates 5714 4.6. Miscellaneous Examples 5714 5. Synthesis of Bridged Lactams with the N−(CO) Bond on a One-Carbon Bridge, ([m.1.n] Type) 5715 5.1. Carbene Insertion Reactions 5715 5.2. Schmidt Reactions 5716 5.3.
“…The first rearrangement was also realized for Quincorine QCI and Quincoridine QCD, after the introduction of iodide as the leaving group (Scheme ). 2 First Rearrangement of QCI and QCD Iodinated at C9: Distinct Pseudoenantiomeric 4 Bridgehead Iminium Ions a + and b + and Their Stereospecific Nucleophilic Capture 6 …”
Stereochemistry, products, and driving forces of the "first and second Cinchona rearrangement" have been investigated and a unified theory is presented. The first cage expansion affords [3.2.2]azabicyclic alpha-amino ether and is formulated via a configurationally stable bridgehead iminium ion and quasiequatorial nucleophilic attack. The second cage expansion affords beta-functionalized [3.2.2]azabicycles. In this case a nonclassical nitrogen-bridged cation is postulated to account for retention of configuration and potential reversibility of the cage expansion. The second rearrangement is favored for the so-called cinch bases (6'-R = H) in trifluoroethanol. Stereoelectronic factors, electron demand at C9, ground state conformation, and solvent type are crucial in all cases. A two-step protocol for preparing 9-epi-configured Cinchona alkaloids from 9-nat precursors is described.
“…139 The corresponding azido compound is formed with high level of stereospecificity. Similarly, α-hydroxy-N-acyl-carbamides generate Nacyliminiums that may be trapped by a variety of nucleophiles, including azidotrimethylsilane, to produce the corresponding azido uracil derivative in high yields and moderate diastereoselectivity (eq 53).…”
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
