In situ generation of 1,5-dipoles by concerted [1,6] hydrogen transfer. Stereoselective thermal rearrangement of 1-(1-pyrrolidinyl)-1,3-butadienes to pyrrolizines

Abstract

1 -(1 -Pyrrolidinyl)-1,3-butadienes (2, 3, 5, and 7), all having an electron-withdrawing substituent at C-3, undergo a thermal rearrangement to pyrrolizine derivatives (1, and 10-14). The rate of reaction generally increases with increasing polarity of the solvent; in aprotic solvents Lewis acids act as catalysts. The rate of reaction is also dependent on the configuration of the l-( 1-pyrrolidinyl)-1,3-butadiene (k^y¡/k(Z)-5 = 5.2). These thermal rearrangements take place in two steps. The first step comprises a concerted antarafacial [1,6] hydrogen shift that generates a 1,5-dipolar species, e.g., 15a, that may undergo stereomutation to 15b; in the second step a disrotatory electrocyclization takes place to give the corresponding pyrrolizines

Mitomycinoid Alkaloids: Mechanism of Action, Biosynthesis, Total Syntheses, and Synthetic Approaches

“…[278] The first step, a [1,6] hydrogen shift, produces a conjugated 1,5 dipolar species ( 299 ) that subsequently undergoes a concerted disrotatory electrocyclization of the 6π- electron system and produces the pyrrolizines. This conjecture was supported by extensive mechanistic analysis including deuterium labeling studies.…”

Tri- and Tetracyclic Azepine Derivatives by Thermally Induced Cyclization of Aminoallenes and Semicyclic 2-Dienamines

“…More recently, Viehe introduced the more descriptive term “α-cyclization of tertiary amines.” Reactions of this type were first observed for tertiary anilines bearing in ortho position a double-bond function with at least one heteroatom 1 ( I , ab: NO, NO 2 , NNR, CNR, CN + R 2 , CO), but it was later realized that the ortho substituent could also be an acceptor-substituted vinyl group. Reinhoudt and co-workers exploited the possibilities of this structural variation extensively, and they were also the first ones to recognize that the essential and sufficient structural moiety to undergo this type of isomerization is that of a N , N -dialkyl-1( Z ),3-dien-1-amine . In the last decade or so, work by Reinhoudt's 4 group and others 2,3,6,7 has amply demonstrated the broad applicability of the reaction principle outlined in Scheme .…”

Mitomycins syntheses: a recent update

“…Reinhoudt illustrated the stereoselective thermal rearrangement of 1-(1-pyrrolidinyl)-1,3-butadienes for the synthesis of mitosane analogs [ 103 – 105 ]. They proposed that the transformation proceeded through two consecutive pericyclic reactions ( Scheme 38 ).…”