S-Methylidene agents: preparation of chiral non-racemic heterocycles

Forbes, David C.; Bettigeri, Sampada V.; Patrawala, Samit A.; Pischek, Susanna C.; Standen, Michael C.

doi:10.1016/j.tet.2008.10.019

Cited by 12 publications

(5 citation statements)

References 35 publications

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“…1 When prepared in situ, this sulfur ylide has been shown to effectively trap aldehydes and ketones to form terminal epoxides and imines to form terminal aziridines 2…”

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confidence: 99%

“…This was validated based upon the isolated yields obtained. Using as a baseline the data obtained when performing methylene transfers with methylphenylsulfonium methylide ii onto aryl substituted chiral non-racemic sulfinyl imines (dr ranging from 66:34 to 87:13),2b we were excited to see such high levels of diastereoselectivity when working with imine 4 (entry 1). The high isolated yield and >95:5 diastereomeric ratio was confirmed when working with ent - 4 (entry 4) While entries 2 and 3 reveal slightly lower levels of stereodiscrimination, these data points support not only the trend within this enantiomeric series ( 5 and ent - 5 ) but a match/mismatch paradigm when performing methylene transfers.…”

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Highly stereoselective methylene transfers onto butanediacetal-protected chiral non-racemic sulfinyl imines using S-ylide technology

2009

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Reaction of sulfur ylide with chiral non-racemic imine afforded the desired aziridine in excellent yield. Diastereomeric ratios of >95:5 were obtained. Both enantiomeric lines of the butanediacetal-protected chiral non-racemic sulfinyl imines were examined. The sulfur ylides were generated in situ upon thermal decarboxylation of carboxylmethyl betaine functionality. The enantiomeric pairs of D-mannitol with (S)-(-)-2-methyl-2-propane sulfinamide and ascorbic acid with (R)-(-)-2-methyl-2-propane sulfinamide resulted in the highest levels of diastereocontrol when performing aziridination reactions.Previously communicated from our laboratory was a novel protocol for the preparation of methylphenylsulfonium methylide ii (Scheme 1). 1 When prepared in situ, this sulfur ylide has been shown to effectively trap aldehydes and ketones to form terminal epoxides and imines to form terminal aziridines. 2 The ease by which sulfur ylide ii is generated is one key advantage of our method over other existing technologies. 3 Generation of the sulfur ylide occurs upon decarboxylation of carboxylmethyl betaine functionality. The process does not require the use of strong and often pyrophoric bases such as butyl lithium or sodium hydride, does not require expensive metal catalysts, and is compatible with ecologically benign solvent systems. However, the 'ease by which the sulfur ylide is generated' as stated above does come at a price. That is, while proficient when considering both scope and levels of conversion, the shortcomings of a protocol which relies on refluxing THF for complete conversion of π-acceptor to heterocycle are notable when considering asymmetry.Our entry into stereoselective methylene transfers began with the use of chiral non-racemic sulfinyl imines (Scheme 2). 2bReaction of thioacetate derivative 1 with a series of aryl substituted chiral non-racemic sulfinyl imines afforded the corresponding aziridines in high yield and good stereoselection. A total of seven systems were examined which consisted of both electron deficient and electron releasing aryl substituted chiral non-racemic imines. Upon in situ generation of the sulfur ylide via the thermally induced decarboxylation of carboxymethylsulfonium betaine functionality, a drop in the diastereomeric ratio was observed when going from electron deficient to electron releasing aryl substituted imines.Correspondence to: David C. Forbes, dforbes@jaguar1.usouthal.edu. NIH Public Access Author ManuscriptChem Commun (Camb) When working at reaction temperatures below refluxing THF, a moderate increase in stereoselection was observed. This was, however, at the expense of percent conversion and still below the level of diastereocontrol reported when working with the less stabilized dimethylsulfonium methylide under identical reaction conditions (dr = 93:7 with dimethylsulfonium methylide (84% isolated yield at room temperature) and dr = 90:10 with methylphenylsulfonium methylide ii (50% conversion at room temperature)).In our search for alternative protocols f...

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“…1 When prepared in situ, this sulfur ylide has been shown to effectively trap aldehydes and ketones to form terminal epoxides and imines to form terminal aziridines 2…”

mentioning

confidence: 99%

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confidence: 99%

Highly stereoselective methylene transfers onto butanediacetal-protected chiral non-racemic sulfinyl imines using S-ylide technology

2009

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“…The use of metal complexes of chiral salen ligands in asymmetric synthesis has been widespread in recent years [5,6]. Numerous metal complexes containing salen derivatives have been synthesized and extensively used as catalysts for a range of asymmetric reactions, such as aziridination [7], cyclopropanation [8], Diels-Alder cycloaddition [9], lactide polymerization [10], Michael addition [11], CO 2 fixation [12], Sulfide oxidation [13], hydrolytic kinetic resolution [14] and so on. Chiral Mn(III) salen complexes have received much interest due to their scope of applications as homogeneous catalysts in asymmetric epoxidation of un-functionalised alkenes, which have been studied extensively by Jacobsen, Katsuki and so on [15,16].…”

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confidence: 99%

Asymmetric Epoxidation of Chromenes Using Manganese(III) Complexes with Novel Chiral Salen-like Schiff Base Ligands

et al. 2012

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Three novel chiral salen-like schiff base ligands and their Mn(III) complexes containing different amino acid unit have been synthesized and characterized. Asymmetric epoxidation reactions show these complexes are effective catalysts for the chromenes with buffer NaOCl as terminal oxidant and pyridine N-oxide as co-catalyst in the presence of ionic liquid. Good-to -excellent enantioselectivity and acceptable yields can be obtained under optimum reaction conditions. Catalyst 4c gives the highest ee (95%) for 6-chloro-2,2-dimethylchromene among these catalytic performances. Furthermore, compared the enantioselectivity of catalyst 4c with the other two catalysts 4a and 4b, the positive experimental results suggest that the steric effect of the ligands plays an important role in the asymmetric catalysis.

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“…Ring closure via an intramolecular nucleophilic attack results in a terminal aziridine/epoxide ring with methylphenyl sulfide as sideproduct. [4] With the particular choice of N -sulfinyl imine 2 , Figure 1, as the target of the addition[5], a high level of diastereocontrol (dr > 95:5) is achieved. Imine 2 has chiral substituents on both the iminyl nitrogen (sulfinyl sulfur atom in the S configuration) and on the iminyl carbon (BDA, as derived from D-mannitol).…”

Section: Introductionmentioning

confidence: 99%

Relative stabilities of transition states determine diastereocontrol in sulfur ylide additions onto chiral N‐sulfinyl imines

Salter¹,

Forbes²,

Wierzbicki³

2011

Int J of Quantum Chemistry

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Additions of methylphenylsulfonium methylide onto chiral non-racemic N-sulfinyl imines (R′-SO-N=CH-R, R′=t-butyl, R=protected diol), followed by ring closure, yield terminal aziridines with high diastereoselectivity. Control reactions have established that both N- and C- iminyl substituents impact product preference, and when properly matched, one addition product is selected almost exclusively. Using solution-phase density functional computational methods, minima and transition state searches have been performed to reveal the structural origins of the diastereoselectivity. Our computational findings indicate that ring closure is fast and irreversible, and consequently, the relative energies of the transition states for the competing Re/Si addition steps determine the product diastereomeric ratios. Analysis of addition transition state structures reveals the causes of selectivity as arising from the N- and C- iminyl substituents, and we identify the S (R) configuration of the N-sulfinyl sulfur atom as the dominant director of Si (Re) addition. The control attributed to the sulfur configuration is tied to an important favorable internal interaction between the sulfinyl oxygen and the iminyl hydrogen. The protected diol acts as a secondary director, owing to steric/electrostatic interactions with the approaching ylide.

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S-Methylidene agents: preparation of chiral non-racemic heterocycles

Cited by 12 publications

References 35 publications

Highly stereoselective methylene transfers onto butanediacetal-protected chiral non-racemic sulfinyl imines using S-ylide technology

Highly stereoselective methylene transfers onto butanediacetal-protected chiral non-racemic sulfinyl imines using S-ylide technology

Asymmetric Epoxidation of Chromenes Using Manganese(III) Complexes with Novel Chiral Salen-like Schiff Base Ligands

Relative stabilities of transition states determine diastereocontrol in sulfur ylide additions onto chiral N‐sulfinyl imines

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