Intramolecular azide-diene cycloadditions. An approach to fused bicyclic 3-pyrrolines based on a one-pot nitrene-diene cycloaddition equivalent.

Abstract

Cyclization of heterosubstituted w-azidodienes 11 provides fused bicyclic 3-pyrrolines 12 in one operation.These pyrrolines are potentially useful intermediates for natural products synthesis, as illustrated by further functionalization.Ring system 1 is well represented as a structural subfeature in many alkaloids.An attractive strategy for the assembly of such systems would be an intramolecular 1,4-nitrene/diene cycloaddition, providing bicyclic 3-pyrrolines 2 (eq. 1). We wish to report herein a one-pot equivalent of this cycloaddition (see 3 =1 5 in Scheme 1).

Asymmetric 1,3-Dipolar Cycloaddition Reactions

“…376 The asymmetric intramolecular 1,3-DC reaction of an azide with one of the alkenes in a conjugated diene has been developed by Hudlicky et al and Pearson et al for the preparation of pyrrolizidine alkaloids. [377][378][379][380][381][382] The general principle of this reaction is outlined in Scheme 56. The azidodiene 411 undergoes an intramolecular 1,3-DC reaction, giving the triazoline 412.…”

“…Elimination of N 2 from 412 gives the vinylaziridine 413 which rearranges to the bicyclic 3-pyrroline 414. [378][379][380] Hudlicky et al have used this approach for the synthesis of pyrrozidine alkaloids such as 416, which was formed as a single isomer, using the chiral substrate 415 (eq 70). 381 Pearson et al studied the influence of the alkoxy group in the allylic position of the diene and found that the cyclization was very smooth, providing only one detectable isomer.…”

“…The azidodiene 411 undergoes an intramolecular 1,3-DC reaction, giving the triazoline 412 . Elimination of N 2 from 412 gives the vinylaziridine 413 which rearranges to the bicyclic 3-pyrroline 414 . − Hudlicky et al have used this approach for the synthesis of pyrrozidine alkaloids such as 416 , which was formed as a single isomer, using the chiral substrate 415 (eq 70) …”

Preparative flash vacuum thermolysis. Selective elimination of 6-chloro-1-hexene from esters of 6-chloro-1-hexanol with Schoenberg rearrangement of the S-methyl xanthate

“…NMR and GC analyses showed that the so obtained colorless liquid (6.4 g, 0.077 mol, yield 90%) was identical with a commercial sample of 4 and that it contained 7% of benzene. 225-Hexen-l-ol (2). 3a (30 g, 0.22 mol) was pyrolyzed in 2 h at 700 °C.…”

Pyrrolizidine and Indolizidine Syntheses Involving 1,3-Dipolar Cycloadditions

“…[141][142][143][144][145][146][147][148][149][150][151] Several total syntheses of racemic pyrrolizidine and indolizidine alkaloids were accomplished in this way. [141][142][143][144][146][147][148][149][150] The enantiodivergent syntheses of trihydroxyheliotridane 6,7-O-acetonide 36 was possible via the chiral azidodiene 35, both enantiomers of which were available from L-and D-erythrose (Scheme 25). 145 A sequence starting from L-glutamic acid and involving the homochiral azidodiene 37 allowed access to (-)-8a-epidesacetoxyslaframine 38 (Scheme 26…”