Nucleophilic Additions to Alkylidene Bis(sulfoxides)—Stereoelectronic Effects in Vinyl Sulfoxides

Abstract

Conjugate additions of nucleophiles (e.g. enolates, amines and malonate anions) to bis(p-tolylsulfinyl)alkenes, alkylidene-1,3-dithiane-1,3-dioxides and alkylidene-1,3-dithiolane-1,3-dioxides have recently been published. Reasons for different selectivities and reaction rates will be discussed by consideration of steric and electronic effects. The preferred mode of attack can be explained by stereoelectronic effects (hyperconjugation) in the primarily carbanion, which is stabilized by n-->S-O-sigma* interaction with an antiperiplanar S=O group. Calculation of the transition states [BP86/aug-TZVP] for the addition of acetone enolate to the dithiane-derived alkylidene bis(sulfoxide) revealed that 6.6-7.3 kJ mol(-1) more energy is needed for an attack leading to a less-stabilized carbanion. Two axial S=O groups in dithiolane-derived alkylidene bis(sulfoxides) lead to a higher reactivity towards nucleophiles.

1,3‐Dipolar Cycloadditions of a 2‐Oxoethanenitrile Oxide Derived from (2R)‐Bornane‐10,2‐sultam to Electronically Modified 4,4′‐Disubstituted Stilbenes

“…The higher reactivity of the minor conformer syn-2 results from a better alignment of the electronic p-system, between both the oxo and the N lp of the sultam moiety. The stereoelectronic properties of such sultam derivatives differ fundamentally from those of simple chiral amides or pyrrolidines, by their N lp anomeric stabilization with the anti-periplanar S¼O s* antibonding orbital [2] [36]. Although the dipolarophile p y trajectory along the C¼O bond precludes the use of the steric rules formerly expressed for this pseudo-C 2 -symmetric auxiliary [11], the observed diastereoselectivity is related to the electronic nature of the dipolarophiles 3a -3i and may be predicted on the basis of either their s para or s stilbene Hammett parameters.…”

Convergent Preparation of Enantiomerically Pure Polyalkylated Cyclopropane Derivatives

“…To prepare nonfunctionalized, enantiomerically enriched disubstituted cyclopropanes (95 % ee), we successfully reported the (À)-sparteine-catalyzed enantioselective carbolithiation [9] of styrenyl derivatives which then undergo a 1,3-elimination reaction. [16] Indeed, when the sulfur ylide, generated in situ by deprotonation of trimethyloxosulfonium iodide with NaH in DMSO, was reacted with alkylidene bis(p-tolylsulfoxides) 3 a-c and corresponding bis(p-tolylsulfinyl)cyclopropanes 2 a-c were obtained in good to excellent diastereoisomeric ratios (Scheme 2). To develop an even more general approach to the preparation of enantiomerically pure polyalkylated cyclopropanes (1; R, R 1 , R 2 = alkyl groups), we envisaged subjecting 2 to a combination of two consecutive selective sulfoxide/lithium exchanges, [12] a transmetalation reaction, and then a reaction with an electrophile (Scheme 1).…”

“…[10] These reactions were restricted to aryl-and vinyl-substituted [10] cyclopropanes. [16] The sulfoxide/lithium exchange occurs when the reactive organometallic reagent reacts at the sulfur center of the sulfoxide, through an S N 2 process, to generate a more stable organometallic leaving group.…”

“…The sulfoxide/lithium exchange occurs when the reactive organometallic reagent reacts at the sulfur center of the sulfoxide, through an S N 2 process, to generate a more stable organometallic leaving group. [16] Indeed, when the sulfur ylide, generated in situ by deprotonation of trimethyloxosulfonium iodide with NaH in DMSO, was reacted with alkylidene bis(p-tolylsulfoxides) 3 a-c and corresponding bis(p-tolylsulfinyl)cyclopropanes 2 a-c were obtained in good to excellent diastereoisomeric ratios (Scheme 2). [16] Indeed, when the sulfur ylide, generated in situ by deprotonation of trimethyloxosulfonium iodide with NaH in DMSO, was reacted with alkylidene bis(p-tolylsulfoxides) 3 a-c and corresponding bis(p-tolylsulfinyl)cyclopropanes 2 a-c were obtained in good to excellent diastereoisomeric ratios (Scheme 2).…”

“…[12f] Alkylidene bis(p-tolylsulfoxides) [12] (3) were recently used as highly versatile partners for asymmetric syntheses [13] in the context of radical chemistry, [14] polar Michael additions, [15] and the Michael-initiated ring closure reaction which is used herein as the key step for the preparation of cyclopropane 2. [16] When 2 a (R = iPr) was treated at low temperature with nBuLi, a selective sulfoxide/lithium exchange took place to give the expected cyclopropyllithium species 5 a, which after methanolysis, afforded cyclopropane 6 a in excellent yield as a single diastereoisomer (Table 1, entry 1). Each of the products 2 b and 2 c were easily separated by column chromatography on silica gel to obtain each diastereoisomer as a pure isomer.…”