6-Diazopenicillanates. Part 1. Reactions with furans

Abstract

Square, London ECI V OHBB enz h y d ry I , pn it ro benzy I , and pival oy loxymet h y I esters of 6diazo penci I la n ic acid u nderg o rhodiumcatalysed reactions with furan giving 6-(4'-oxobut-2-enylidene) penicillanates in high yields. Substitution on the furan ring results in a strong steric effect at the 2-position and reveals the detrimental effects of electron-withdrawing groups at positions 2 and 3. The absence of a marked steric effect in 3-methylfuran indicates that the reaction does not involve initial, direct cyclopropanation, contrary t o earlier claims. Addition of the 6-diazopenicillanate to benzofuran provides the first reported example of a carbenoid ring expansion of the latter.

Intermolecular reactions of electron-rich heterocycles with copper and rhodium carbenoids

“…30 A more recent example of this reaction using Rh 2 (OAc) 4 isolated the exo isomer 84a exclusively in moderate yield. 31 Acceptor-acceptor substituted carbenoids. Rh 2 (OAc) 4 -catalyzed decomposition of 2-diazo-1,3-cyclohexanedione 19 in the presence of benzofuran 83 yields two regiomeric cycloadducts 85 and 86, arising from competition between initial bond formation at the 2-and 3-positions (eqn ( 11)).…”

Rh(II)-Catalyzed Spirocyclization of α-Diazo Homophthalimides with Cyclic Ethers

“…In conclusion, we have described the first systematically investigated case of a cyclic metal carbene insertion into the C–O bond of a cyclic ether molecule leading to the formation of a spirocyclic scaffold. Apart from two isolated cases of such insertion encountered in the literature, , oxonium ylides (presumably involved in the formation of the observed spirocycles) have been almost exclusively shown to undergo an alternative [1,4]-shift of an oxonium alkyl group to the carbonyl oxygen atom, which results in the formation of a fused bicylic (or a macrocyclic) system. , The tendency of homophthalimide metal carbene-derived oxonium species to preferably undergo the Stevens-type [1,2]-alkyl migration has been corroborated by the quantum chemical calculations. More in-depth computational analysis currently underway in our laboratories is aimed at evaluating possible transition states of the observed vs potentially competing tranfromations ([1,4]-alkyl shift or C–H insertion).…”

“…Ring expansion of cyclic ethers via the Stevens-type rearrangement of the oxonium ylides generated from acyclic α-diazocarbonyl compounds (Figure , pathway a ) is rather common and has been amply exemplified since the pioneering publication of Gutsche . However, the respective cyclic ether ring expansions involving cyclic α-diazocarbonyl compounds, which would provide an intriguing entry into spirocyclic scaffolds, have not been described in the literature, except for the isolated examples of (i) an insertion of a photochemically generated carbene into the C–O bond of tetrahydrofuran and (ii) a somewhat unusual C–O insertion of 6-diazopenicillanate into the benzofuran molecule . Although we viewed it as a surprising void (considering the recent developments in the synthesis of thiaspirocyles via the Stevens rearrangement of cyclic sulfonium ylides), we thought it could be attributable to the preference of the oxonium counterparts of the latter to undergo [1,4]-shift (Figure , pathway b ) to give a fused bicyclic rather than a spirocyclic system ,,, and/or an α-diazocarbonyl moiety.…”

Spirocyclizations Involving Oxonium Ylides Derived from Cyclic α-Diazocarbonyl Compounds: An Entry into 6-Oxa-2-azaspiro[4.5]decane Scaffold

“…However, the uses of cyclic α-diazocarbonyl compounds as partners in similar transformations of cyclic ethers (which would provide a productive entry into spirocyclic frameworks) are surprisingly scarce. Until recently, only two examples of such spirocyclizations were reported in literature: (a) carbene insertion into the C–O bond of tetrahydrofuran under photochemical conditions and (b) Rh 2 (OAc) 4 -catalyzed C–O insertion of 6-diazopenicillinate into the benzofuran core . We reasoned that this gaping synthetic methodology void (particularly puzzling in light of the recently reported thiaspirocycle synthesis from cyclic sulfonium ylides) could be attributed to the possible preference of the respective oxonium ylides to follow pathway b , i.e., [1,4]-shift, rather than the Stevens rearrangement, and afford a fused bicyclic rather than a spirocyclic system. , However, in 2019, we discovered and reported the first systematically studied example of Rh­(II)-catalyzed spirocyclization of α-diazo homophthalimides with cyclic ethers and demonstrated, using quantum chemical calculations performed at the B3LYP/6-31G* level of theory, that said spirocyclization (Stevens type rearrangement, pathway a ) was indeed preferred over the formation of a fused bicycle ([1.4]-shift, pathway b ) .…”