Development of the [3 + 2] Annulations of Cyclohexenylsilanes and Chlorosulfonyl Isocyanate:  Application to the Total Synthesis of (±)-Peduncularine

Abstract

The synthesis of (+/-)-peduncularine was accomplished using the [3 + 2] annulation of an allylic silane with chlorosulfonyl isocyanate to assemble the bicyclic core of the alkaloid. The stereochemistry of the annulation product was employed to control the installation of the indolylmethyl side chain at C-7 with complete stereoselectivity.

Tris-[8]annulenyl Isocyanurate Trianion Triradical and Hexa-anion from the Alkali Metal Reduction of [8]Annulenyl Isocyanate

“…The reduction of C 8 H 7 NCO under vacuum conditions in hexamethylphosphoramide (HMPA) at 293 K with sodium metal, 31 or in THF (with 1 equiv of 18-crown-6) with potassium metal at 180 K, gives rise to an EPR spectrum that upon computer simulation reveals that the anion radical of a substituted [8]annulene had been generated, Figure 1. 32,33 The two larger a H 's (4.13 G (2 Hs) and 4.37 G (2 Hs)) come from coupling to the four hydrogens on the even numbered carbons, while the smaller a H (2.295 G (3 Hs)) is from the hydrogens on the odd numbered carbons.…”

“…33b, 34 On the basis of the EPR results obtained, our initial conclusion was that we had successfully generated the anion radical of C 8 H 7 NCO in solution for two important reasons: (1) The unpaired electron clearly resides within the annulene ring and exhibits coupling to only one nitrogen atom (a N = 0.58 G) and (2) in previous studies with PhNCO •− , we found that the NCO Scheme 1. Synthesis of [8]Annulenyl Isocyanate (1) Starting from Cyclooctatetraene (COT) Figure 1. (Upper) X-band EPR spectrum recorded at 180 K after a THF solution containing [8]annulenyl isocyanate (C 8 H 7 NCO) with 1 equiv of 18-crown-6 was exposed to K metal under vacuum.…”

“…28 To further our understanding of the stability and the reactivity of isocyanate anion radicals, we are motivated to investigate the reduction of [8]annulenyl isocyanate (C 8 H 7 NCO, 1), which is a new isocyanate and its chemistry has yet to be explored. We believe this to be an ideal molecular system for further exploration of isocyanate reduction chemistry since we anticipate that much of electron density will reside within the [8]annulenyl ring upon addition of an electron. This is a consequence of the expected high electron affinity (EA) of the [8]annulenyl moiety in 1.…”

“…This is a consequence of the expected high electron affinity (EA) of the [8]annulenyl moiety in 1. (The EA of [8]annulene (cyclooctatetraene, COT) is +63 kJ/mol. 29 ) If substantial attenuation of spin density away from the NCO group occurs, how will this impact the reactivity of 1 •− ?…”

“…29 ) If substantial attenuation of spin density away from the NCO group occurs, how will this impact the reactivity of 1 •− ? Additionally, 1 is a particularly attractive system to explore due to the fundamental quantum mechanical differences between [8]annulene (4n π electrons) and [6]annulene (4n + 2 π electrons). Therefore, the reduction chemistry of C 8 H 7 NCO is an interesting choice to compare with that of the already explored PhNCO.…”