Stereoselective Construction of Seven-Membered Rings with an All-Carbon Quaternary Center by Direct Tiffeneau−Demjanov-type Ring Expansion

Abstract

Insertion of one methylene unit into the C-C bond of cyclohexanones is a potentially useful, straightforward method for the construction of seven-membered carbocycles. An especially appealing but largely unexplored method in this arena is the nucleophilic addition of diazoalkanes to the Lewis acid-activated cyclohexanones and subsequent ring expansion accompanied by the extrusion of nitrogen (direct Tiffeneau-Demjanov-type ring expansion). Our primary finding is the unprecedented insertion of alpha-alkyldiazoacetates to cyclohexanone and its heteroanalogues, generating seven-membered rings with one all-carbon quaternary center. On the basis of this finding, highly diastereoselective ring expansion of substituted cyclohexanones was developed, furnishing seven-membered rings with 1,4-quaternary-tertiary, 1,4-quaternary-quaternary, or 1,3,5-quaternary-tertiary-tertiary stereogenic centers in a single operation starting from readily available materials. The stereochemical outcome of the product can be easily predicted from the conformation of starting cyclohexanones. Enantioenriched products could be also accessed by the use of (-)-phenylmenthyl alpha-alkyldiazoacetates.

Catalyst‐Free Intramolecular Formal Carbon Insertion into σ‐CC Bonds: A New Approach toward Phenanthrols and Naphthols

“…On the other hand, the corresponding formal CC bond insertion (Scheme , when R′=alkyl or aryl) is more challenging because of the relatively low reactivity and the difficulty associated with the selectivity of the 1,2‐shift. Recently, the studies by Kingsbury,1g, 2e,h,j Maruoka,1f, 2d,f,g,i Feng,1h, 2k and other groups have significantly promoted the development of this area, particularly the stereocontrol of the reaction.…”

Stereoselective Csp3–Csp2 Bond‐Forming Reactions by Transition‐Metal‐Free Reductive Coupling of Cyclic Tosylhydrazones with Boronic Acids

“…In ap revious communication, [10] we showed that two differentd oubleb ond regioisomers-theo lefination product A or the reductivea lkenylation derivative B,r espectively,c an be obtained depending on the nature of both coupling partners, and in at otally predictable manner (Scheme1a). Interestingly,i nasingle particular example when a4 -substituted cyclohexanonew as employed, the coupling reactionp roceeded with total diastereo-selectivity leading to the reductive alkenylation product as as ingle diasteroisomer.Iti snoteworthy that an important limitation of the reactions basedo ns ulfonylhydrazoneso rd iazo compounds that proceed without the need of am etal catalyst is their lack of stereocontrol; [11] therefore, this particular reaction was indeed ar are example of ad iastereoselective reaction based on diazo compounds in the absence of am etal catalyst. [12] Ta king into consideration the ample synthetic possibilities that these reductivec ouplings offer,w ed ecided to investigate in more detail the stereoselectivity of these metal-free Csp 3 À Csp 2 bond-forming reactions.…”

Biorelevant Metals in Sustainable Metal Catalysis—A Survey

“…The activation of diazo compounds for carbene‐transfer chemistry is commonly achieved by using oxidized transition‐metal complexes/salts. Recently, Maruoka was able to show that BF 3 is also a potent Lewis acid catalyst for diastereoselective Tiffeneau–Demjanov‐type ring expansions (Scheme ) 29. This report certainly represents an important expansion in the field of boron catalysis, as it showcases the fact that under certain conditions boron‐containing complexes can possess metal‐like reactivities.…”