A Two-Directional Synthesis of (+)-β-Isosparteine

A two-directional synthesis of (+)-β-isosparteine is described in five steps from glutaric acid, where the entire carbon and nitrogen backbone of the alkaloid, possessing the requisite relative and absolute stereochemistry at its four stereogenic centers, is assembled using a double imino-aldol reaction

A Two-Directional Synthesis of (+)-β-Isosparteine

A two-directional synthesis of (+)-β-isosparteine is described in five steps from glutaric acid, where the entire carbon and nitrogen backbone of the alkaloid, possessing the requisite relative and absolute stereochemistry at its four stereogenic centers, is assembled using a double imino-aldol reaction

Diastereoselective Syntheses of (3<i>R*</i>,4<i>R*</i>)- and (3<i>R*</i>,4<i>S*</i>)‑4-Aryl-3-methyl-4-piperidinemethanol and Fluoro Analogues

Two concise and high-yielding diastereoselective syntheses of 4-aryl-3-methyl-4-piperidinemethanols were realized from 1,3-dimethyl-4-piperidinone. The key reactions to control the C3–C4 relative stereochemistry were the alkoxymethylation of a metalloenamine generated from 4-aryl-3-methyl-1,2,3,6-tetrahydropyridine that afforded the (3<i>R*</i>,4<i>S*</i>)-form and the nucleophilic substitution of a fluoroarene with deprotonated 3-methyl-4-piperidinenitrile giving the (<i>3R*</i>,4<i>R*</i>)-isomer. The corresponding fluoromethyl analogues were subsequently obtained through the fluorination of the piperidinemethanols using DAST

Total Synthesis of the Tetracyclic Lupin Alkaloid (+)-Allomatrine

(+)-Allomatrine (<b>1</b>) has been synthesized using an imino-aldol reaction and <i>N</i>-acyliminium cyclization as key steps. Strategically, use of the <i>tert</i>-butylsulfinimine derivative of (<i>E</i>)-4-(trimethylsilyl)but-2-enal enabled the staged formation of three C–C bonds, a C–N bond, and the four stereogenic centers within the target

<i>N</i>‑Heterocyclic Carbene-Mediated Microfluidic Oxidative Electrosynthesis of Amides from Aldehydes

A flow process for <i>N</i>-Heterocyclic Carbene (NHC)-mediated anodic oxidative amidation of aldehydes is described, employing an undivided microfluidic electrolysis cell to oxidize Breslow intermediates. After electrochemical oxidation, the reaction of the intermediate <i>N</i>-acylated thiazolium cation with primary amines is completed by passage through a heating cell to achieve high conversion in a single pass. The flow mixing regimen circumvented the issue of competing imine formation between the aldehyde and amine substrates, which otherwise prevented formation of the desired product. High yields (71–99%), productivities (up to 2.6 g h^–1), and current efficiencies (65–91%) were realized for 19 amides

Long-Lived Nuclear Singlet Order in Near-Equivalent ¹³C Spin Pairs

Molecules that support ¹³C singlet states with lifetimes of over 10 min in solution have been designed and synthesized. The ¹³C₂ spin pairs in the asymmetric alkyne derivatives are close to magnetic equivalence, so the ¹³C long-lived singlet states are stable in high magnetic field and do not require maintenance by a radiofrequency spin-locking field. We suggest a model of singlet relaxation by fluctuating chemical shift anisotropy tensors combined with leakage associated with slightly broken magnetic equivalence. Theoretical estimates of singlet relaxation rates are compared with experimental values. Relaxation due to antisymmetric shielding tensor components is significant

Long-Lived Nuclear Singlet Order in Near-Equivalent ¹³C Spin Pairs

Molecules that support ¹³C singlet states with lifetimes of over 10 min in solution have been designed and synthesized. The ¹³C₂ spin pairs in the asymmetric alkyne derivatives are close to magnetic equivalence, so the ¹³C long-lived singlet states are stable in high magnetic field and do not require maintenance by a radiofrequency spin-locking field. We suggest a model of singlet relaxation by fluctuating chemical shift anisotropy tensors combined with leakage associated with slightly broken magnetic equivalence. Theoretical estimates of singlet relaxation rates are compared with experimental values. Relaxation due to antisymmetric shielding tensor components is significant

Long-Lived Nuclear Singlet Order in Near-Equivalent ¹³C Spin Pairs

Molecules that support ¹³C singlet states with lifetimes of over 10 min in solution have been designed and synthesized. The ¹³C₂ spin pairs in the asymmetric alkyne derivatives are close to magnetic equivalence, so the ¹³C long-lived singlet states are stable in high magnetic field and do not require maintenance by a radiofrequency spin-locking field. We suggest a model of singlet relaxation by fluctuating chemical shift anisotropy tensors combined with leakage associated with slightly broken magnetic equivalence. Theoretical estimates of singlet relaxation rates are compared with experimental values. Relaxation due to antisymmetric shielding tensor components is significant

Recycling and Imaging of Nuclear Singlet Hyperpolarization

The strong enhancement of NMR signals achieved by hyperpolarization decays, at best, with a time constant of a few minutes. Here, we show that a combination of long-lived singlet states, molecular design, magnetic field cycling, and specific radiofrequency pulse sequences allows repeated observation of the same batch of polarized nuclei over a period of 30 min and more. We report a recycling protocol in which the enhanced nuclear polarization achieved by dissolution-DNP is observed with full intensity and then returned to singlet order. MRI experiments may be run on a portion of the available spin polarization, while the remaining is preserved and made available for a later use. An analogy is drawn with a “spin bank” or “resealable container” in which highly polarized spin order may be deposited and retrieved

Synthesis of an Isotopically Labeled Naphthalene Derivative That Supports a Long-Lived Nuclear Singlet State

The synthesis of an octa-alkoxy substituted isotopically labeled naphthalene derivative, shown to have excellent properties in singlet NMR experiments, is described. This highly substituted naphthalene system, which incorporates an adjacent ¹³C spin pair, is readily accessed from a commercially available ¹³C₂-labeled building block via sequential thermal alkynyl- and arylcyclobutenone rearrangements. The synthetic route incorporates a simple desymmetrization approach leading to a small difference in the chemical shifts of the ¹³C spin pair, a design constraint crucial for accessing nuclear singlet order