A Mild and General Solid-Phase Method for the Synthesis of Chiral Polyamines. Solution Studies on the Cleavage of Borane−Amine Intermediates from the Reduction of Secondary Amides
Bibliographic record
Abstract
A mild oxidative workup protocol using iodine in an acetic acid-acetate buffer solution is described for the cleavage of borane-amine adducts arising from the borane-promoted reduction of polyamides supported onto practical trityl-based resins. Chiral polyamines with diverse side-chain functionalities can be generated as free bases without premature release from the solid support and with essentially no racemization using this method. A series of model oligomeric secondary diamides 6 containing various alpha-amino acid residues (Val, Phe, Tyr, Ser, Cys, Met, Gln, Trp) provided triamine products 8 in high yields and good to excellent purity. On the other hand, a substrate containing a tertiary amide (15) formed a rather unusual triaminoborane intermediate that required more stringent workup conditions to liberate the polyamine product 20. The reduction of oligomeric tertiary amides such as 9 was found sluggish, but these compounds could nonetheless be obtained in high purity from in situ reductive amination of the corresponding secondary amines. Control studies, carried out in solution with model secondary amide 23, confirmed the efficiency of the buffered iodine solution and highlighted several advantages (no heating necessary, no need for strong bases or acids) over existing methods for the cleavage of borane-amine adducts. A possible mechanism involving all buffer components (iodine, acetic acid, and acetate ion) is proposed in which borane-amine adducts are transformed first to the monoiodoborane-amine and then to the corresponding acetoxyborane-amine adduct of much weaker coordination affinity. The latter would dissociate readily and get trapped by the acetic acid to provide the desired secondary amine. This reduction/oxidative workup protocol is useful as a general method for the facile solid-phase synthesis of polyamines for eventual release in solution and use in various applications. It is also potentially very useful toward the synthesis and screening of bead-supported libraries of free oligoamines assembled through split-pool methods.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one teacher head, not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".