Wolfgang Kirmse

100 Years of the Wolff Rearrangement

The conversion of α-diazo ketones into ketenes, and products derived therefrom, was discovered by Wolff in 1902. Major applications of the Wolff rearrangement, such as the Arndt−Eistert reaction (homologation of carboxylic acids) and the ring contraction of cyclic ketones, have been with us for some while. Nevertheless, substantial progress has been made recently. The reaction mechanism has been explored by means of matrix isolation, time-resolved spectroscopy, and computation. Full retention of configuration of the migrating group has been established by using enantioselective chromatography. The Arndt−Eistert reaction has witnessed a renaissance in the field of natural products, in particular β-amino acids and β-peptides. Ring-contracting Wolff rearrangements and ketene cycloadditions have been applied in syntheses of increasingly complex, biologically active target molecules. These accomplishments, as well as unsolved problems, are addressed in the present review. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

Oxygen ylides. I: Reactions of carbenes with oxetane

Abstract The ylides generated from carbenes (:CH 2 , :CHCO 2 Et, :CHPh) and oxetane in the presence of methanol undergo Stevens rearrangement and protonation competitively, yielding tetrahydrofurans and 1,3-dialkoxycyclopropanes as major products.

Oxygen ylides. II: Photochemical and rhodium-catalyzed reactions of diazomethane with (S)-2-methyloxetane

Abstract Photolysis of diazomethane in (S)-2-methyloxetane gives 2- and 3-methyltetrahydrofuran (1:3.2), the latter being formed with 21 % net retention of configuration. In contrast, rhodium acetate catalysis yields racemic 3-methyltetrahydrofuran exclusively.

Intramolecular reactivity of arylcarbenes: 2-(Alkoxymethyl)phenylcarbenes

Abstract Both singlet and triplet states contribute to the intramolecular CH insertion reactions of 2- (alkoxymethyl)phenylcarbenes, leading to dihydro-1 H -2-benzopyrans. Competitively, oxygen ylides are generated which eventually give rise to benzocyclobutenes and dihydroisobenzofurans. The radical pair mechanism of the Stevens rearrangement is confirmed by variation of the alkyl groups and by means of chiral substrates.

Carbenes and the O–H bond: norbornenylidenes

Bicyclo[2.2.1]hept-2-en-7-ylidene 10 and bicyclo[2.2.1]hept-5-en-2-ylidene 21 are shown to react with methanol by way of proton transfer, with formation of norborneyl cations.

Reactivity of Functionalized Arylcarbenes. 2-Phenylethyl Side Chains and Hetero Analogues

Abstract Phenylcarbenes with -X-CH 2 Ph and -CH 2 -X-Ph (X = CH 2 , O, SiMe 2 ) groups in the ortho position were generated thermally and photolytically from diazo or tosylhydrazone precursors. Stereorandom insertion reactions with β-C-H bonds were observed, pointing to a triplet abstraction-recombination mechanism. Large kinetic and stereochemical deuterium isotope effects support this notion. The ample formation of benzocyclobutenes from 2-CH 2 -X-Ph substrates is due to insertion of the carbenes into ArCH 2 -X bonds. Addition to the terminal phenyl groups competes with C-H and C-X insertion. The results of benzophenone sensitization and of trapping with methanol suggest that the intramolecular reactions of functionalized arylcarbenes proceed, at best, competitively with spin inversion.

Intramolecular Reactivity of Triplet Carbonylcarbenes

Through a double cyclization triplet carbonylcarbenes add smoothly to double bonds in the δ and ε position, but do not react intramolecularly with C-H bonds (see scheme). The addition reaction fails if the keto group is replaced with an ester group.

Nucleophilic displacement of methide from silicon. Steric compression of geminal trimethylsilyl groups

6,6-Bis(trimethylsilyl)norbornan-endo-2-ol (6) undergoes base-induced intramolecular displacement of a Si–Me group with formation of (9), in contrast to the monosilylated analogue (7).

Biphotonic generation of carbenes and carbocations by laser flash photolysis

Abstract In protic solvents, trans-2,3-diphenylaziridinylimines of diaryl ketones are (flash-)photolyzed in two consecutive steps, via diaryldiazomethanes and diarylcarbenes, to give eventually diarylmethyl cations. The same intermediates arise from diazo ketones by way of Wolff rearrangement and ketene photolysis. The method has been used to demonstrate the protonation of fluorenylidene by hexafluoroisopropanol.

Intramolecular reactivity of arylcarbenes: Biphenyl‐2‐ylcarbenes

Biphenyl-2-ylcarbenes, 2-ArC6H4CR, were generated photolytically and thermally from diazo precursors. Cyclization, leading to fluorenes, competes with capture of the carbenes by methanol but proceeds faster than intramolecular hydrogen shifts (with R = Me) and intermolecular C(SINGLE BOND)H insertion reactions (with R = H in cyclohexane). By comparison of product ratios with kinetic data for related carbenes from the literature, the cyclization rate is estimated as ca 1011s−1. The intramolecular reactivity of biphenyl-2-ylcarbenes is not significantly attenuated by variation of R (R = H, Me, Ph). Very minor effects of triplet sensitization and methanol quenching indicate that fluorenes arise from spin-equilibrated biphenyl-2-ylcarbenes, presumably from the singlet state. When Ar = mesityl, the carbene predominantly inserts into C(SINGLE BOND)H bonds of the 2′-methyl groups, giving rise to a dihydrophenanthrene. Formation of a fluorene derivative, by formal insertion into C(SINGLE BOND)C bonds, occurs as a minor process. This unprecedented reaction points to intervention of an o-xylylene in which the methyl group migrates. Laser flash photolysis (LFP) of 2-PhC6H4CN2Ph generates a transient absorption which is due to the T0 Tn transition of 9-phenylfluorene rather than to the presumed o-xylylene. On LFP of 2-ArC6H4CN2Ph in trifluoroethanol-acetonitrile, protonation of the carbenes gives rise to carbocations, 2-ArC6H4CH+Ph. The transient absorption spectra of these cations are strongly influenced by twisting about the Ar(SINGLE BOND)Ar bond (Ar = Ph < o-tolyl < mesityl) whereas the rates of nucleophilic capture vary only slightly. Biphenyl-2-ylcarbenium ions (Ar = R = Ph) cyclize more slowly than the analogous carbenes, by a factor of ≥104.