Alkaloid inspired spirocyclic oxindoles from 1,3-dipolar cycloaddition of pyridinium ylides

Abstract

Cycloaddition reactions between pyridinium ylides and 3-alkenyl oxindoles that proceed in high yield and with very good regio- and diastereoselectivity are reported. The resulting cycloadducts have the same stereochemistry of biologically active oxindole alkaloids, such as strychnofoline.

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds

“…The reaction of 3-cyanopyridine with tert-butyl diazoacetate and oxindole 1 gave a mixture of two diastereoisomers 8 in a 90% combined yield and diastereomeric ratio of about 3:2, the minor component corresponding to inversion of the spirocentre. [24] Subsequently, a reaction performed on 1.3 mmol scale with 0.25 mol% of Fe(TPP)Cl gave cycloadduct 9 in good yield (83%) but lower catalysts loadings (0.1 mol%) gave inferior yields (25%).…”

“…Bromopyridines featuring another substituent were also effective reagents.F or example,c ycloadducts 6 and 7 were prepared in 80 and 53 %y ield from 3bromo-5-methoxypyridinea nd 3-bromo-4-methylpyridine, respectively.T he reaction of 3-cyanopyridine with tert-butyl diazoacetate and oxindole 1 gave amixture of two diastereoisomers 8 in 90 %c ombined yield and with ad iastereomeric ratio of about 3:2, the minor component corresponding to inversion of the spirocenter. [24] Subsequently,areaction performed on a1 .3 mmol scale with 0.25 mol %o f[ Fe-(TPP)Cl] gave cycloadduct 9 in good yield (83 %);t he yield decreased to 25 %when alower catalyst loading (0.1 mol %) was used.…”

“…The NMR data of 2 suggested that the sense of diastereoselectivity was the same as related products prepared by conventional base-promoted ylide formation. [24] Cyclopropane 3 was obtained as the only product when Rh 2 (OAc) 4 (1 mol%) was used as the catalyst, however. A catalyst loading of 1 mol% of Fe(TPP)Cl in toluene led to similar yields of 2 (89%), so these conditions were used.…”

Stereoselective Synthesis of Tetrahydroindolizines through the Catalytic Formation of Pyridinium Ylides from Diazo Compounds

“…Satisfyingly, tetrahydroindolizidine 2 was obtained as the sole product in good yield (89–90 %) as a single diastereoisomer when 5 mol % of either [Fe(TPP)Cl] (TPP=tetraphenylporphyrin) or [(MeCN) 4 CuPF 6 ] was used. The NMR data of 2 suggested that the sense of diastereoselectivity was the same as that for related products prepared by conventional base‐promoted ylide formation . However, cyclopropane 3 was obtained as the only product when [Rh 2 (OAc) 4 ] (1 mol %) was used as the catalyst.…”

Visible‐Light‐Induced Carbo‐2‐pyridylation of Electron‐Deficient Alkenes with Pyridinium Salts

“…[9] To explore such astrategy,weproposed that af ormal dicarbofunctionalization of electron-deficient alkenes with pyridinium salts should be achieved. The proposed reaction pathway is shown in Scheme 1B:i )dearomative 1,3-dipolar cycloaddition of ylides [10] and electrondeficient alkenes (syn addition to alkene) to construct the dienamine moiety 4 [11] (previously formed by condensation of amine and a,b-unsaturated aldehyde [2a-d] ), ii)absorption of visible light and subsequent intersystem crossing (ISC) process to yield the triplet excited state of the dienamine moiety 5,iii)intramolecular electron-transfer from the triplet dienamine moiety [12] to the acceptor to generate the triplet zwitterionic biradical intermediate 6,i v) proton transfer to produce the neutral biradical 7, [13] v) ISC process followed by formal aza-Norrish II cleavage of the 1,4-biradical intermediate [14] to open the five-membered ring, vi)tautomerization to complete the desired carbo-2-pyridylation reaction. In contrast, with an external radical source (such as TEMPO, oxygen, etc.…”