Cascade Radical Cyclizations via Biradicals Generated from (Z)-1,2,4-Heptatrien-6-ynes

Abstract

On heating in refluxing benzene, acyclic enyne-allene 4 underwent intramolecular transformations in a sequence with an initial Myers cycloaromatization to form R,3-didehydrotoluene biradical 5 followed by a 5-exo cyclization of the benzenoid radical center in 5 to produce 6. Biradical 6 then decayed through a 1,5-hydrogen shift to furnish o-quinodimethane 7, which in turn was captured in an intramolecular Diels-Alder reaction to afford 8 having the tetracyclic steroidal skeleton in a single step from 4 in 50% isolated yield. Similarly, acyclic enyneallene 16 having one of the tethers shortened by one carbon atom furnished 18 having the fused 5,6,6,5-ring system. Tetracycle 19 substituted with an angular methyl group was obtained from 17. In the cases of 24 and 34, a predominant 1,5-hydrogen shift of an allylic hydrogen to the benzenoid radical center of biradicals 26 and 35 followed by a homolytic coupling produced spiro derivatives 31 and 40, respectively. On the other hand, a preferential 7-endo ring closure of biradicals 41 and 49, derived from 25 and 48, gave predominantly the tricyclic derivatives 46 and 54, respectively. Similarly, cascade radical cyclizations via biradicals generated from enyne-allenes 67-70 produced the bicyclic spiro compounds 77-80 having a four-membered ring.

Alkyne Elementometalation−Pd-Catalyzed Cross-Coupling. Toward Synthesis of All Conceivable Types of Acyclic Alkenes in High Yields, Efficiently, Selectively, Economically, and Safely: “Green” Way

“…To avoid this difficulty, use of the second Negishi coupling via B→I72-74 and even B→I→Li74 transformations have been reported as more satisfactory, if circuitous, alternatives.…”

Trimethylenemethane Diyl Mediated Tandem Cycloaddition Reactions: Mechanism Based Design of Synthetic Strategies

“…10 Extension of the radical cascade reaction into diradical reaction also provided quick entry into polycyclic structures in one operation (Figure 1). 11 Another reactive intermediate, carbene 12 could be used to increase the complexity of the system through design of a strategy that utilizes the interesting nature of carbene that is equivalent to zwitterionic species 7b or diradical species. We became interested in utilizing carbene intermediate to generate diradical intermediate for tandem reaction strategy.…”

Highly Regio- and Stereoselective Synthesis of (Z)-Trisubstituted Alkenes via Propyne Bromoboration and Tandem Pd-Catalyzed Cross-Coupling

“…Subsequent Pd-catalyzed cross-coupling would provide a potentially selective route to trisubstituted alkenes of unprecedentedly wide scope. Although this was realized first by Suzuki in 1988 with a Pd-catalyzed tandem Negishi–Suzuki coupling process5 and more recently by Wang6 with a double Negishi coupling process, these previous studies collectively fell short of the above-stated promise. Notably, in the single most desirable case of propyne haloboration for the selective synthesis of ( Z )-alkene-containing terpenoids, all reported stereoselectivity values were ≤89% 6c,8,9.…”

“…Although this was realized first by Suzuki in 1988 with a Pd-catalyzed tandem Negishi–Suzuki coupling process5 and more recently by Wang6 with a double Negishi coupling process, these previous studies collectively fell short of the above-stated promise. Notably, in the single most desirable case of propyne haloboration for the selective synthesis of ( Z )-alkene-containing terpenoids, all reported stereoselectivity values were ≤89% 6c,8,9. Secondly, although haloboration itself appears to proceed satisfactorily not only with alkyl-substituted alkynes but also with other types of alkynes substituted with Ph and cyclohexenyl,8a,9a,10 those subjected to Pd-catalyzed cross-coupling have been strictly limited to the cases of alkyl-substituted alkynes 5–7…”