Rearrangements of α-Diazo-β-hydroxyketones for the Synthesis of Bicyclo[m.n.1]alkanones

Abstract

Rhodium-catalyzed decomposition of fused bicyclic α-diazo-β-hydroxyketones results in good yields of bridged bicyclo[m.n.1]ketones via a rearrangement pathway.

Preparation and Synthetic Applications of Five-to-Seven-Membered Cyclic α-Diazo Monocarbonyl Compounds

“…A separate case is represented by the synthesis of β-hydroxy-α-diazo cyclic ketones—an important class of diazo compounds. The most common way to access such building blocks is with a base-promoted intramolecular addition of a terminal diazo ketone to another carbonyl group (as shown for the preparation of 10 ) [ 24 , 25 , 26 ]. More simple derivatives of this class can be accessed from the respective diazo dicarbonyl compounds (such as 11 ) by desymmetrizing the reduction of one of the carbonyl groups ( Scheme 7 ) [ 27 ].…”

“…Since both carbon–carbon bonds leading to this hydroxy group can be fragmented, two products ( 44 and 45 ) can be formed in varying ratios. It is supposed that the alkyl migration takes place as a concerted process, which is supported by the preserved stereochemistry of the α-carbon atom ( Scheme 28 ) [ 24 ].…”

“…In the case of γ’-methoxy substitution (as in 46 ), along with the rearrangement product ( 47 ), a substantial amount of intramolecular C-H insertion product 48 is formed, which is indicative of the reaction proceeding through rhodium carbenes. Additional evidence that the catalyst does not act as a Lewis acid is that the reaction is not workable with acidic catalysts (HCl or BF 3 ·Et 2 O), in which case only products 49 of the dehydration of the starting alcohol are formed ( Scheme 29 ) [ 24 ].…”

“…Going from a five-membered cycle ( 52 ) to a six-membered cycle ( 53 ), the amount of the path b rearrangement product is increased. Due to stereochemical and energetic considerations, the formation of a cyclopentanone ring ( 54 ) is more preferred compared to a cyclobutene ring ( 55 ) ( Scheme 30 ) [ 24 ].…”

Synthesis of cis-hydrindan-2,4-diones bearing an all-carbon quaternary center by a Danheiser annulation

“…Almost all the strategies developed to date involve the formation of the C3–C3a bond in the ring-closing step leading to the hydrindane nucleus. The carbocyclization takes place from polyfunctionalized cyclohexanones or related compounds through a Michael reaction [ 7 ], successive inter- and intramolecular radical processes [ 8 ], intramolecular carbene addition/cyclization [ 9 – 10 ], aldol cyclizations either under Lewis acid catalysis [ 11 ] or from diazoketones in the presence of bases (e.g., DBU) [ 12 ], Pd-catalyzed cycloalkenylation of a silyl enol ether [ 13 ], or base-promoted ynone carbocyclizations [ 14 – 15 ]. Another approach through an aldol cyclization, forming the C1–C7a bond instead, has also been reported [ 16 ].…”