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Divergent Electrochemical Carboamidation of Cyclic Amines
Wang, Feijun ; Frankowski, Kevin J. ; JOC,2022,87(2):1173-1193. DOI: 10.1021/acs.joc.1c02534 PubMed ID: 34985905
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Abstract: We developed an electrochemical carboamidation sequence that affords either cyclic β-amidoamine products via direct functionalization or linear hydroxybisamide products via a ring opening pathway. The reaction pathway was dependent on the nature of the N-acyl activating group, with carbamate groups favoring direct isocyanide addition to the N-acyliminium ion intermediate and the benzoyl activating group favoring the ring opening–functionalization pathway. Both protocols are one-pot reaction sequences, have general applicability, and lead to peptide-like products of greatly increased molecular complexity.
Purchased from AmBeed: 943516-54-9 ; 86953-79-9 ; 75844-69-8 ; 36635-61-7 ; 75178-87-9 ; 35018-15-6 ; 22110-53-8 ; 138350-92-2 ; 69838-98-8 ; 57224-51-8 ; 55379-71-0 ; 123387-52-0 ; 58644-53-4 ; 1549912-21-1 ; 56475-80-0 ; 97846-69-0 ...More
CAS No. : | 86953-79-9 | MDL No. : | MFCD00216581 |
Formula : | C9H17NO2 | Boiling Point : | - |
Linear Structure Formula : | (C4H8N)COOC(CH3)3 | InChI Key : | LPQZERIRKRYGGM-UHFFFAOYSA-N |
M.W : | 171.24 | Pubchem ID : | 643455 |
Synonyms : |
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Signal Word: | Warning | Class: | N/A |
Precautionary Statements: | P261-P305+P351+P338 | UN#: | N/A |
Hazard Statements: | H315-H319-H335 | Packing Group: | N/A |
GHS Pictogram: |
* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
27% | Step 1: sec-Butyl lithium (25.3 mL, 35.4 mmol) was added into a solution of tert-butyl 1-pyrrolidinecarboxylate (6.2 mL, 35.4 mmol) and (-)-spartiene (8.29 g, 35.4 mmol) in MTBE (100 mL) at -78C. The mixture was stirred for 1 hour at -78C. Zinc chloride solution (35.4 mL, 35.4 mmol) was added, and the reaction was stirred for 15 minutes at -78C. The reaction was allowed to warm up to room temperature. 4- Bromoindolin-2-one (5.00 g, 23.6 mmol), palladium (II) acetate (0.53 g, 2.4 mmol) and tri- tert-butylphosphine tetrafluoroborate (0.68 g, 2.4 mmol) was added into the reaction mixture. The reaction was stirred for 12 hours at room temperature. The reaction mixture was poured into EtOAc (200 mL), and the suspension was filtered with a pad of celite. The filtrate was concentrated, and the residue was purified by flash chromatography (silica gel eluted with 4:1 hexanes : ethyl acetate) to give (R)-tert-butyl 2-(2-oxoindolin-4-yl)pyrrolidine-l-carboxylate (1.9 g, 27%) as a solid. 1H NMR (CDCl3, 400 MHz) delta 7.80 (s, IH), 7.10-7.20 (m, IH), 6.75- 6.82 (m, IH), 6.62-6.78 (m, IH), 4.65-4.93 (m, IH), 3.34-3.73 (m, 4H), 2.20-2.40 (m, IH), 1.84-2.00 (m, 2H), 1.68-1.83 (m, IH), 1.45 (2, 4H), 1.14 (s, 5H). MS (APCI+) [M+H]+ 303. |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
9% | With sec.-butyllithium; In tetrahydrofuran; cyclohexane; at -78℃; for 3.0h;Inert atmosphere; | A flame dried round bottom flask equipped with a magnetic stir bar was charged with N-Boc-pyrrolidine (10g, 58mmol, 1eq) and dry THF (40mL) under a nitrogen atmosphere. The clear colorless solution was cooled to -78C and a solution of s-BuLi (64mL of a 1.0M solution in cyclohexane, 64mmol) was added slowly over a 30min period. The light orange colored solution was stirred at -78C for 3h followed by treatment with B(OMe)3 (15mL, 175mmol) after which the cooling bath was removed and the clear colorless solution slowly warmed to 0C. Upon reaching 0C, the reaction was quenched with a small amount of water (?2mL), allowed to warm to room temp then extracted into 2N NaOH (100mL) and backwashed with additional EtOAc (60mL). The aqueous phase was acidified to pH 3 by the addition of 2N HCl and then extracted with EtOAc (3×60mL). The organic extracts were combined and dried over Na2SO4 and concentrated to produce the free boronic acid 9g as a sticky white solid. Without further purification the boronic acid was dissolved in EtOAc (60mL) and with constant stirring (+)-pinanediol (7.0g, 41mmol) was added at room temperature. After 18h the ester was removed and the (+)-pinanediol boronic ester was purified by column chromatography (silica gel, 6:1 hexanes/EtOAc) to give a clear thick oil (12.1g, 34.8mmol) 60% yield in two steps. 1H NMR (400MHz, CDCl3) delta 4.50-4.15 (m, 1H), 3.38 (dt, J=13.8, 6.1Hz, 2H), 3.12 (ddd, J=25.1, 15.8, 8.4Hz, 1H), 2.33 (dd, J=12.3, 10.3Hz, 1H), 2.20 (s, 1H), 2.10-1.69 (m, 7H), 1.45 (d, J=7.3Hz, 9H), 1.41 (s, 3H), 1.28 (s, 3H), 0.84 (s, 3H). |
Yield | Reaction Conditions | Operation in experiment |
---|---|---|
N-Boc-pyrrolidine (2g, 11.7mmol) under nitrogenDissolved in 30 mL of re-distilled anhydrous THF, the solution was cooled to -78 C,A solution of s-BuLi in hexane (14 mmol) was slowly added over 30 min.Then, stirring was continued at -78 C for 3 h;Treated with B(OMe)3 (3.9 mL, 35 mmol),After that, the temperature was slowly raised to about 0 C, and the reaction was quenched with a small amount of water (about 0.5 mL).After warming to room temperature, extract with 2N NaOH (25 mL) solution.The aqueous phase was adjusted to pH=3 by adding 2N hydrochloric acid to the aqueous phase.Extract with ethyl acetate (3 x 20 mL) and combine the organic phases.Drying over anhydrous sodium sulfate and evaporating the solvent gave a white viscous solid.The yield was 84%.The crude product was used in the next reaction without purification. |
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