Stoichiometric and Catalytic (η 5-Cyclopentadienyl)cobalt-Mediated Cycloisomerizations of Ene-Yne-Ene Type Allyl Propargyl Ethers

Abstract

The complexes CpCoL2 (Cp = C5H5; L = CO or CH2=CH2) mediate the cycloisomerizations of α,δ,ω-enynenes containing allylic ether linkages to 3-(oxacyclopentyl or cycloalkyl)furans via the intermediacy of isolable CpCo-η 4-dienes. A suggested mechanism comprises initial complexation of the triple bond and one of the double bonds, then oxidative coupling to a cobalt-2-cyclopentene, terminal double bond insertion to assemble a cobalta-4-cycloheptene, β-hydride elimination, and reductive elimination to furnish a CpCo-η 4-diene. When possible, the cascade continues through cobalt-mediated hydride shifts and dissociation of the aromatic furan ring. The outcome of a deuterium labeling experiment supports this hypothesis. The reaction exhibits variable stereoselectivity with a preference for the trans-product (or, when arrested, its syn-Me CpCo-η 4-diene precursor), but is completely regioselective in cases in which the two alkyne substituents are differentiated electronically by the presence or absence of an embedded oxygen. Regioselectivity is also attained by steric discrimination or blocking one of the two possible β-hydride elimination pathways. When furan formation is obviated by such regiocontrol, the sequence terminates in a stable CpCo-η 4-diene complex. The conversion of the cyclohexane-fused substrate methylidene-2-[5-(2-propenyloxy)-3-pentynyl]cyclohexane into mainly 1-[(1R*,3aS*,7aS*)-7a-methyloctahydroinden-1-yl]-1-ethanone demonstrates the potential utility of the method in complex synthesis.

The Trajectory of the (η 5-Cyclopentadienyl)cobalt-Mediated Cycloisomerization of Ene-Yne-Ene-Type Allyl Propargylic Ethers to Furans: A DFT Appraisal

“…Intriguingly, removing two of the methyl groups from 1-Me 4 , as in 1-Me 2 (Scheme 3), reinstated the cycloisomerization pathway, which proceeded with complete regio-selectivity, -hydride elimination engaging exclusively the more hindered side. 1 Gratifyingly, the experimental results were reproduced computationally (Figure 10). Thus, both cis (blue) and trans (green) cobaltacycloheptene intermediates Turning to the unobserved exocyclic counterpart of the above -hydride eliminations involving the hydrogens of one of the methyl groups of IN2Me 2 and leading to a skipped diene topology, calculations reveal relatively higher Next to be examined was the regioselectivity observed in the cycloisomerization of 1-Deoxy, which stops at the stage of the deoxy analogue of 2, engendering 2-Deoxy syn and anti (with respect to the positioning of the methyl substituent and CpCo, ratio 2:1), in turn derived from the corresponding trans-and cis-cobaltacycloheptene isomers, and exhibits -hydride elimination exclusively from the non-oxygen containing ring (Scheme 4).…”

“…Having established the qualitative and quantitative details of Scheme 1, computational attention turned to understanding the effects of structural variations in the order reported in the experimental account. 1 The first to be addressed concerned the failure of 1,4-bis[(3-methyl-2butenyl)oxy]but-2-yne (1-Me 4 ), in which 1 has been exhaustingly adorned with terminal additional methyl groups, to undergo cycloisomerization. Instead, two molecules of the starting material combine to couple the individual triple bonds and one of the appended double bonds to furnish the [2+2+2] cycloaddition product (Scheme 2).…”

“…This paper aims to provide answers to these queries by a DFT computational scrutiny of the basic conversion of 1 into 3, as well as that of variants of 1 that were investigated in our experimental work. 1 The intramolecular cyclization of dienynes has not been the subject of computational analysis, and we hope that our results will provide an increased understanding of related experimental investigations. 3 In addition, some of the computed individual steps bear some similarity to calculated transformations in the literature, providing a corresponding complement.…”

“…We recently reported on the cycloisomerizations of ,,-enynenes containing allylic ether linkages mediated catalytically and stoichiometrically by CpCoL 2 (Cp = C 5 H 5 ; L = CO or CH 2 =CH 2 ) to furnish 3-(oxacyclopentyl or cycloalkyl)furans via the intermediacy of isolable CpCo-η 4 -dienes. 1 In the simplest case, substrate 1 was seen to convert into trans isomer 3 with catalytic CpCo(CO) 2 in boiling and irradiated PhMe in 70% yield, while intermediate 2 could be intercepted when 1 was exposed to one equivalent of CpCo(CH 2 =CH 2 ) at 0 °C, also in 70% yield. In both cases, inspection of the crude reaction mixtures by 1 H NMR revealed the presence of 2-3% of the corresponding stereoisomers.…”

“…1 In the simplest case, substrate 1 was seen to convert into trans isomer 3 with catalytic CpCo(CO) 2 in boiling and irradiated PhMe in 70% yield, while intermediate 2 could be intercepted when 1 was exposed to one equivalent of CpCo(CH 2 =CH 2 ) at 0 °C, also in 70% yield. In both cases, inspection of the crude reaction mixtures by 1 H NMR revealed the presence of 2-3% of the corresponding stereoisomers. A very tentative mechanism was formulated based on related art 2,3 and geared toward reproducing the syn (methyl to Cp-Co) stereochemistry in 2 and the trans constitution of 3 (Scheme 1).…”