The R amberg‐ B äcklund Rearrangement

Abstract

The halogen atoms of α‐halo sulfones, in contrast to halogen atoms α to other electron‐withdrawing functionalities, show marked resistance to substitution by external nucleophiles. Seemingly, polar, steric, and field effects combine to repel nucleophilic species. However, the same α‐sulfonyl halogen atoms are capable of facile intramolecular 1,3 elimination, leading to replacement of the sulfonyl group by a carboncarbon double bond with loss of halide and sulfite ions. This extrusion process, frequently referred to as the α‐halo sulfone or Ramberg‐Bäcklund rearrangement after its discoverers, has found broad utility in olefin synthesis. The reaction is generally applicable and easy to use. Its earliest application dealt with the preparation of alkenes, the cis isomers of which predominated. Whereas such molecules may be more readily available by other methods, none of the alternative procedures offers the added option of specifically replacing the olefinic hydrogen atoms with deuterium by merely conducting the rearrangement in deuterated solvents. Moreover, because the α‐halo sulfones undergo this transformation in alkaline solution, further rearrangement of the initially formed alkenes is precluded. Therefore the SO 2 group in the starting sulfone is invariably replaced cleanly and unequivocally by the π bond. The rearrangement is generally applicable to molecules containing the minimal structural requirements of a sulfonyl group, an α‐halogen atom, and at least one α′‐hydrogen atom, even in systems leading to small‐ring cycloalkenes. Di‐ and tri‐halo sulfones behave analogously. Conformational constraints, adverse hybridization characteristics, and excessive strain are known to deter the reaction. Inasmuch as these features arise only in special circumstances, they do not necessarily detract from its usefulness. This chapter summarizes the more important advances in the understanding of α‐halo sulfone rearrangements, particular consideration being given to the nature of the intermediates, scope of the available synthetic alternatives, optimization of experimental conditions, and effect of structural features on reactivity. Closely related transformations are also discussed.

Radical Alliances: Solutions and Opportunities for Organic Synthesis

“…[126] The xanthate group in the adducts constitutes a convenient entry into all of organosulfur chemistry. The RambergÀ Bäcklund olefin forming reaction, [92][93] the numerous reactions involving sulfur ylides, and the rich chemistry of sulfones can all participate in mutually enriching symbiotic alliances with the radical chemistry of xanthates.…”

“…[91] In our case, not only did the HWE condensation on diketone 212 take place smoothly, but the product 213 contains a xanthate group on C(11) that could later be used to introduce the exo-methylene group found in Desogestrel, for example by a RambergÀ Bäcklund reaction. [92,93] An alternative way to exploit the HWE condensation is to have the phosphonate on the alkene and the xanthate attached to the ketone. This variant is illustrated by the transformations in Scheme 33.…”

Fenton-Inspired C–H Functionalization: Peroxide-Directed C–H Thioetherification

“…Sulfoxides are well-known for enabling syn eliminations, Mislow–Evans rearrangements, , Pummerer reactions, , and sulfoxide–metal exchanges , while also acting as a useful ligand class for transition metal catalysis . The higher-oxidation state sulfones also provide ample opportunities in organic synthesis, most notably as alkene precursors in the Julia–Lythgoe olefination, , Kocienski-modified Julia olefination, , and Ramberg–Bäcklund rearrangement. , A recent report has also highlighted the utility of sulfones as radical cross-coupling partners . The preparation of alkyl thioethers generally proceeds through nucleophilic displacement of a (pseudo)­halide with a thiol or the trapping of an alkyl radical or organometallic nucleophile with a disulfide .…”

Unusual heterocyclisation in the transformation of 6-halomethylsulfonyl-substituted bicyclo[3.1.1]heptane under Ramberg–Bäcklund reaction conditions

“…The transformation of alcohol 5 into methylenic derivative 3 is believed to result from the Ramberg-Bäcklund reaction 8 and occurs in a tandem process of 1,3-dehydrobromination to give episulfone 9 followed by its desulfonation. Although attempts at detecting episulfone 9 during the treatment of alcohol 5 with a base failed, it may be assumed that the stereochemistry of alcohol 5 1,3-dehydrobromination is the same as that of ether 6.…”

“…Although attempts at detecting episulfone 9 during the treatment of alcohol 5 with a base failed, it may be assumed that the stereochemistry of alcohol 5 1,3-dehydrobromination is the same as that of ether 6. Furthermore, literature precedents 8,9 suggest that α-bromosulfones 5 and 6 should indeed undergo stereoselective dehydrobromination to give episulfones 9 and 8, respectively, since it has been found that elimination obeys the W-stereochemistry 10 and the α-proton is abstracted from a conformation of the starting bromosulfone in which it is flanked by oxygen atoms of the sulfo group. Thus, alcohol 3 is formed due to fragmentation of episulfone 9 and is a 'normal' product of the Ramberg-Bäcklund reaction (Scheme 3).…”