Synthesis of Polysubstituted Ferrocenesulfoxides

Abstract

The purpose of the study is to design synthetic methodologies, especially directed deprotometalation using polar organometallic reagents, to access polysubstituted ferrocenesulfoxides. From enantiopure 2-substituted (SiMe3, PPh2) S-tert-butylferrocenesulfoxides, a third substituent was first introduced at the 5 position (SiMe3, I, D, C(OH)Ph2, Me, PPh2, CH2NMe2, F) and removal of the trimethylsilyl group then afforded 2-substituted ferrocenesulfoxides unreachable otherwise. Attempts to apply the “halogen dance” reaction to the ferrocenesulfoxide series led to unexpected results although rationalized in light of calculated pKa values. Further functionalizations were also possible. Thus, new enantiopure, planar chiral di- and trisubstituted ferrocenes have been obtained, in addition to several original 2-substituted, 2,3- and 2,5-disubstituted, 2,3,5-trisubstituted and even 2,3,4,5-tetrasubstituted ferrocenesulfoxides, also enantiopure.

Exploring the boundaries of ferrocenesulfonyl fluoride chemistry

“…167 As a result, XB have recently been observed for iodoferrocenes substituted with sulfonamides, 54 sulfonates 55 and sulfoxides. 87 For the 1,2,3,4-tetrasubstituted ferrocene 6d , halogen bonds were observed between the iodine atom and the nitrogen lone-pair of the pyridine ring (I1⋯N15 3.219(4) Å, C6–I1⋯N15 158.27(11) °). As a result of the iodine and nitrogen atom pointing in opposite directions, linear strings of XB, one for each enantiomer, are observed in the crystal structure (Fig.…”

“…After methanolysis, the desired product 6a was isolated in 62% yield together with 22% of the deiodinated product 3a, resulting from a competitive lithium/iodine exchange, as already reported in the literature. 55,56,82,83,87 Pleasingly, it was possible to perform the reaction on a 16 mmol scale with slightly better results (6a, 79% yield). Using Eschenmoser's salt to trap the lithiated intermediate afforded the 1,2,3,4-tetrasubstituted derivative 6b in 68% yield while the use of methyl chloroformate only afforded the ester 6c in a surprising low 2% yield.…”

“…Evidenced in the ferrocene series in 2010, 81 the 'halogen dance' reaction has been successfully extended to various ferrocene derivatives and currently represents a valuable synthetic tool to reach original derivatives. 47,[54][55][56][82][83][84][85][86][87] Typical substrates combine a powerful directing group (DG) and a protecting group (PG) to prevent a competitive deprotolithiation of the otherwise activated free position (Scheme 4, top). A smart way to compare the ability of different directing groups to trigger the 'halogen dance' reaction is to compare the calculated pK a values of a series of Please do not adjust margins Please do not adjust margins isomerized product (Scheme 4, bottom).…”

“…167 As a result, XB have recently been observed for iodoferrocenes substituted with sulfonamides, 54 sulfonates 55 and sulfoxides. 87 169 A zig-zag chain of XB, involving both enantiomers, is observed at the solid-state and probably results from the proximal position of the chlorine and ester substituents (Figure 9, bottom). As expected, the oxygen-iodine and oxygen-chlorine bonds lengths were below the sum of the corresponding van der Waals radii (3.50 Å for OI and 3.27 Å for OCl).…”

Unravelling functions of halogen substituents in the enantioseparation of halogenated planar chiral ferrocenes on polysaccharide-based chiral stationary phases: experimental and electrostatic potential analyses

“…Since, halogenated ferrocenes have appeared as key intermediates for accessing polysubstituted ferrocenes [12]. More recently, iodinated ferrocenes turned out to be involved in halogen bond (XB) in solid state [13,14], and even in solution with emerging application as organocatalyst in organic synthesis [13,15].…”