Configurational Stability of Carbanions Stabilized by d-Orbitals

Cram, Donald J.; Partos, Richard D.; Pine, Stanley H.; Jäger, Herb.

doi:10.1021/ja00868a054

Cited by 9 publications

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“…We measured the ratio of the isomers 25 and 26 by integration of the well-resolved methoxy signals in the 'H NMR spectra, and we assigned structures by making the methyl ester 26 of an authentic sample'' of the corresponding carboxylic acid 32. The equilibrium ratio for the esters25 and 26 was 34:66. In the phenyl ketone series, we prepared the enolate 28 by conjugate addition of lithium Ph uph Me1 Ph dph ; + P h 4 P…”

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confidence: 98%

The diastereoselectivity of electrophilic attack on trigonal carbon adjacent to a stereogenic centre: diastereoselective alkylation and protonation of open-chain enolates having a stereogenic centre at the ? position

Fleming¹,

Lewis²

1992

J. Chem. Soc., Perkin Trans. 1

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Methylation of the enolates 7, 24, 28 and 33 and protonation of the enolates 10, 27, 31 and 36 are diastereoselective in conformity to a general rule, summarised in the drawing 1, governing the stereochemistry of electrophilic attack on a double bond adjacent to a stereogenic centre. The sense of the selectivity is, with one exception, opposite to that of the corresponding nucleophilic attack on a carbonyl group adjacent to a stereogenic centre, which, with the same exception, follows Cram's and the Felkin-Anh rule, summarised in the drawing 2. The exception is probably the reduction 40+ 38 + 39, with 39 as the major product. This result is inconsistent with Cram's and the Felkin-Anh rule if the isopropyl group is counted as 'larger' than the phenyl group, whereas the Grignard reaction 37-38 + 39, where 39 is again the major product, and the corresponding electrophilic reactions 33 -34 + 35, with 34 as the major product, and 36 + 34 + 35, with 35 as the major product, are all consistent with isopropyl being effectively larger than phenyl.For some years we have been studying the diastereoselectivity of electrophilic attack on a C=C double bond adjacent to a stereogenic centre in the general sense 1. Our interest in thistype of diastereoselectivity stems from our discovery, in several types of open-chain structure, of high levels of selectivity, with many applications in organic synthesis, when the large group, L, is a silyl group, and the small group, S, is hydrogen. Our interest was further stimulated by the realisation that this type of diastereoselectivity, even without a silyl group being present, was much less well studied, in spite of its fundamental nature, than the corresponding nucleophilic attack on trigonal carbon-the reaction of nucleophiles with carbonyl groups having an adjacent stereogenic centre, first systematised by Cram 30 years before we began our work, and explained with a transition structure 2, with successive refinements by Karbatsos,' Felkin,3 and Anh and their c o -~o r k e r s . ~ We present, in this and the following eight papers, all of our work to date in this area, with the exception of that which has already appeared in full,5 and that which relates to natural product synthesis, which will follow in a second series of papers. To set the scene, we discuss here the steric factors that are either known or expected to affect the diastereoselectivity, and we also report our experiments on a simple enolate system with only carbon groups on the stereogenic centre, designed to provide a paradigm for this type of selectivity, and reported already in preliminary form.6At the end of the present series we append a tenth paper summarising our results and conclusions. Less dedicated readers might like to turn to that paper now. t Results and DiscussionElectrophilic Attack on Trigonal Carbon Adjacent to a Stereogenic Centre.-Early work in this area7 was largely t I. Fleming, J. Chem. SOC.,

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The diastereoselectivity of electrophilic attack on trigonal carbon adjacent to a stereogenic centre: diastereoselective alkylation and protonation of open-chain enolates having a stereogenic centre at the ? position

Fleming¹,

Lewis²

1992

J. Chem. Soc., Perkin Trans. 1

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“…In contrast to ordinary diazoalkanes, diazocyclopentadiene ( 1 ) is not attacked at C-1 by electrophiles, but at C–H positions, preferentially at C-2, thus giving rise to electrophilic aromatic substitutions. In 1963, Cram and Partos reported several electrophilic aromatic substitutions of 1 , 13 for example, nitration to occur at C-2 and C-3, azo coupling with benzenediazonium ion at C-2, bromination with N -bromosuccinimide to give tetrabromodiazocyclopentadiene, 14 and mercuration with Hg(OAc) 2 at C-2 and C-5. While 1 underwent a [ π 8 s + π 2 s ] cycloaddition with dimethyl acetylenedicarboxylate, electrophilic substitution at C-2 occurred with tetracyanoethylene.…”

Section: Table 1 Rate Constants and Eyring Activation P...mentioning

confidence: 99%

“…Weaker Michael acceptors might undergo concerted cycloadditions with 1 , however, as previously reported for the reactions of alkynes with 1 and further substituted diazocyclopentadienes. 13 34…”

Section: Table 1 Rate Constants and Eyring Activation P...mentioning

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Elucidation of the Nucleophilic Potential of Diazocyclopentadiene

Mayr¹,

Hartnagel²,

Ofial³

2022

Synthesis

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Diazocyclopentadiene reacts with benzhydrylium ions (Ar2CH+) to give 2,5-dibenzhydryl-substituted diazocyclopentadienes. The kinetics have been determined photometrically in dichloromethane under pseudo-first-order conditions using diazocyclopentadiene in excess. Plots of the second-order rate constants (log k 2) versus the electrophilicity parameters E of the benzhydrylium ions gave the nucleophilicity parameter N = 4.84 and susceptibility s N = 1.06 for diazocyclopentadiene according to the correlation log k(20 °C) = s N(E + N). Diazocyclopentadiene thus has a similar nucleophilic reactivity as pyrrole. Previously reported electrophilic substitutions of diazocyclopentadiene are rationalized by these parameters and new reaction possibilities are predicted.

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“…Not only the latter, but also ionic carbanions, can be configurationally stable, for instance if the carbanion is strongly pyramidalized, as some metalated sulfones [533][534][535], or if inversion is precluded by the structure of the carbanion, as for bridgehead carbanions. Not only the latter, but also ionic carbanions, can be configurationally stable, for instance if the carbanion is strongly pyramidalized, as some metalated sulfones [533][534][535], or if inversion is precluded by the structure of the carbanion, as for bridgehead carbanions.…”

Section: 48mentioning

confidence: 99%

The Alkylation of Carbanions

Dörwald

2004

Side Reactions in Organic Synthesis

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The deprotonation of organic compounds by strong, non-nucleophilic bases followed by C-alkylation with a suitable electrophile has become one of the most predictable and straightforward methods for formation of C-C bonds. The popularity of this chemistry is also a consequence of the often-seen close resemblance of feasible structural modifications by a deprotonation/alkylation strategy to an unsophisticated retrosynthetic analysis of a given target compound. Other reactions, which involve, for instance, substantial rearrangement of the carbon framework (e.g. Cope rearrangement, fragmentations, ring contractions or enlargements) are usually more difficult to take into account during retrosynthetic analysis.LDA and related, sterically hindered, lithium dialkylamides, first investigated by Levine [1], have completely replaced the more nucleophilic sodium amide, which had been the base of choice for many years [2]. Because the reactivity of an organometallic compound depends to a large extent on its state of aggregation (i.e. on the solvent and on additives) and on the metal, transmetalation of the lithiated intermediates and the choice of different solvents and additives emerged as powerful strategies for fine-tuning the reactivity of these valuable nucleophiles.In this chapter the alkylation of carbanions with simple carbon electrophiles will be discussed, with special emphasis on the structure-reactivity relationship of the carbanion and on side reactions. In this context the term "carbanion" refers to an intermediate prepared by in-situ deprotonation of an organic compound, followed by optional cation exchange (transmetalation), which tends to be alkylated at carbon by soft electrophiles such as MeI or PhCHO. This type of reactivity is characteristic of enolates with an ionic M-O bond or for organometallic compounds with a strongly polarized or ionic M-C bond, M typically being an alkali metal, Mg, Cu, or Zn. Carbanions can, alternatively, also be prepared by halogen-metal exchange [3-8], sulfoxide-or sulfone-metal exchange [9-13], or by transmetalation of stannanes. The most suitable reagents for performing such metalating exchange reactions are organometallic compounds with a metal-bound secondary or tertiary alkyl group, such as tBuLi, sBuLi, iPr 2 Zn [14, 15], or iPrMgHal [6]. These reagents are thermodynamically less stable than organometallic compounds with primary alkyl 5 146 Scheme 5.1. Approximate relative rates of proton transfer in water at thermoneutrality (DpK a = 0) [35, 39, 51]. 147 Scheme 5.2. The effect of fluorine on the acidity of organic compounds [24, 62-65]. 148 Scheme 5.3. Dependence of the reactivity of carbanions on their basicity [68, 72-74]. Regioselectivity of Deprotonations and AlkylationsThe organic chemist is occasionally confronted with the problem that a compound has several differrent X-H groups of similar pK a . If only one of these is to be alkylated, one option would be to perform a regioselective deprotonation. This can sometimes be achieved by exploiting small differences be...

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Configurational Stability of Carbanions Stabilized by d-Orbitals

Cited by 9 publications

References 0 publications

The diastereoselectivity of electrophilic attack on trigonal carbon adjacent to a stereogenic centre: diastereoselective alkylation and protonation of open-chain enolates having a stereogenic centre at the ? position

The diastereoselectivity of electrophilic attack on trigonal carbon adjacent to a stereogenic centre: diastereoselective alkylation and protonation of open-chain enolates having a stereogenic centre at the ? position

Elucidation of the Nucleophilic Potential of Diazocyclopentadiene

The Alkylation of Carbanions

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