New Initiation Modes for Directed Carbonylative C–C Bond Activation: Rhodium-Catalyzed (3 + 1 + 2) Cycloadditions of Aminomethylcyclopropanes

Under carbonylative conditions, neutral Rh(I)-systems modified with weak donor ligands (AsPh3 or 1,4-oxathiane) undergo N-Cbz, N-benzoyl, or N-Ts directed insertion into the proximal C–C bond of aminomethylcyclopropanes to generate rhodacyclopentanone intermediates. These are trapped by N-tethered alkenes to provide complex perhydroisoindoles.


S25
compound 8i (32.2 mg, 64 %) as a colorless oil. A mixture of diastereomers A and B were obtained in a 8:1 (A:B) ratio. Under general procedure H, title compound 8i was obtained in 61 % yield (30.7

mg) as a colorless oil. A mixture of diastereomers A and B were obtained in a 3:1 (A:B) ratio.
The relative stereochemistry of major diastereomer A was corroborated by nOe experiments (as indicated on the compound structure). A nOe was observed between C1-H and C10-H, and no significant nOe was observed between C5-H and C10-H. The stereochemical assignment of major diastereomer A is consistent with that of major diastereomer A of 8l.
The relative stereochemistry of minor diastereomer B was tentatively assigned by analogy to that of minor diastereomer B of 8l.

The relative stereochemistry of major diastereomer A was corroborated by nOe experiments (as indicated on the compound structure). A nOe between C2b-H and C7-H was observed, and no significant nOe was observed between C7-H and C12-H. The stereochemical assignment of major diastereomer A is consistent with that of major diastereomer A of 8l.
The relative stereochemistry of minor diastereomer B was tentatively assigned by analogy to that of minor diastereomer B of 8l.  1, 138.1, 135.7, 129.4, 127.2, 116.6, 61.6, 32.7, 21.5, 18.2, 18
Then MeCN/H2O(1:1, 1 mL) was added and the reaction tube was sealed under an argon atmosphere and heated to 80 °C for 2 h. The reaction mixture was cooled to r.t. and diluted with H2O (5 mL). The aqueous phase was extracted with EtOAc (3 x 5 mL), the combined organic layers were washed with brine, dried over Na2SO4 and concentrated in vacuo. The
Then evacuated and back-fill the flask with hydrogen three times. The reaction was stirred at 40 o C for 18 hours. The reaction mixture was then filtered through a short plug of silica, washed with MeOH, and concentrated in vacuo to afford 8h' as a colorless oil which was directly dissolved in anhydrous toluene (2.0 ml), and then potassium carbonate (41.4 mg, 0.3 mmol) and sulfonyl chloride (57.0 mg, 0.3 mmol) were added to the solution. The reaction mixture was heated to 50 °C and stirred overnight. The suspension was cooled to r.t. and water (5 mL) was added, the aqueous layer was extracted with EtOAc (3 × 5 mL) and the S80 organic extracts combined, dried over Na2SO4 and concentrated in vacuo. The crude mixture was purified by column chromatography (33 % EtOAc/Hex) to yield the title compound 8i (24.7 mg, 51 %) as a colorless oil. A mixture of diastereomers A and B were obtained in a 9:1 ratio.