Organocatalytic Stereoselective α‐Alkylation of Aldehydes with Stable Carbocations

Benfatti, Fides; Benedetto, Elena; Cozzi, Pier Giorgio

doi:10.1002/asia.201000160

Cited by 104 publications

(22 citation statements)

References 81 publications

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“…On the other hand, when stable and isolable carbenium ions were tested (Scheme 10), the reaction occurred without problems. [77] Recently we were also exploring, in collaboration with Dr. Barbero in Turin, other stabilized carbenium ions, [78] which were also studied by Mayr. [79] Again the electrophilicity was perfectly suitable for reactivity and for allowing the isolation of these stable carbenium ions.…”

Section: An Unexpected Journey: Carbenium Ions For Organocatalytic S mentioning

confidence: 98%

“…Not only water can compete for the reaction with the unstable carbenium ion, but it is quite important to mention that the concentration of enamine in catalytic reactions can be quite low,76 and other less nucleophilic species can be more effective, because their concentration is higher. On the other hand, when stable and isolable carbenium ions were tested (Scheme ), the reaction occurred without problems 77…”

Section: An Unexpected Journey: Carbenium Ions For Organocatalytic Snmentioning

confidence: 99%

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From QCA (Quantum Cellular Automata) to Organocatalytic Reactions with Stabilized Carbenium Ions

Gualandi

Mengozzi

Manoni

et al. 2016

The Chemical Record

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What do quantum cellular automata (QCA), "on water" reactions, and SN 1-type organocatalytic transformations have in common? The link between these distant arguments is the practical access to useful intermediates and key products through the use of stabilized carbenium ions. Over 10 years, starting with a carbenium ion bearing a ferrocenyl group, to the 1,3-benzodithiolylium carbenium ion, our group has exploited the use of these intermediates in useful and practical synthetic transformations. In particular, we have applied the use of carbenium ions to stereoselective organocatalytic alkylation reactions, showing a possible solution for the "holy grail of organocatalysis". Examples of the use of these quite stabilized intermediates are now also considered in organometallic chemistry. On the other hand, the stable carbenium ions are also applied to tailored molecules adapted to quantum cellular automata, a new possible paradigm for computation. Carbenium ions are not a problem, they can be a/the solution!

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Section: An Unexpected Journey: Carbenium Ions For Organocatalytic S mentioning

confidence: 98%

Section: An Unexpected Journey: Carbenium Ions For Organocatalytic Snmentioning

confidence: 99%

From QCA (Quantum Cellular Automata) to Organocatalytic Reactions with Stabilized Carbenium Ions

Gualandi

Mengozzi

Manoni

et al. 2016

The Chemical Record

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“…19 now explains why the Jørgensen-Hayashi diphenylprolinol trimethylsilyl ether [81], the precursor of 32b , and structurally related pyrrolidines have previously been employed for catalyzing the reactions of aldehydes and ketones with weak electrophiles, such as β-nitrostyrene ( E = –13.9) [85] or di- tert -butyl azodicarboxylate ( E = –12.2) [86]. The less basic imidazolidinones, which yield the less nucleophilic enamines 32d and 32e , are suitable catalysts for reactions with stronger electrophiles, such as the chlorinating agent 2,3,4,5,6,6-hexachlorocyclohexan-2,4-dien-1-one ( E = –6.75) [87] and, in particular, stabilized carbocations, which are generated in situ from the corresponding alcohols under weakly acidic conditions [14,88–89]. Suggestions for further promising electrophilic reaction partners in enamine activated reactions [90] can be derived from the electrophilicity scales in [4].…”

Section: Reviewmentioning

confidence: 99%

A quantitative approach to nucleophilic organocatalysis

Mayr¹,

Lakhdar²,

Maji³

et al. 2012

Beilstein J. Org. Chem.

132

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SummaryThe key steps in most organocatalytic cyclizations are the reactions of electrophiles with nucleophiles. Their rates can be calculated by the linear free-energy relationship log k(20 °C) = s N(E + N), where electrophiles are characterized by one parameter (E) and nucleophiles are characterized by the solvent-dependent nucleophilicity (N) and sensitivity (s N) parameters.Electrophilicity parameters in the range –10 < E < –5 were determined for iminium ions derived from cinnamaldehyde and common organocatalysts, such as pyrrolidines and imidazolidinones, by studying the rates of their reactions with reference nucleophiles. Iminium activated reactions of α,β-unsaturated aldehydes can, therefore, be expected to proceed with nucleophiles of 2 < N < 14, because such nucleophiles are strong enough to react with iminium ions but weak enough not to react with their precursor aldehydes. With the N parameters of enamines derived from phenylacetaldehyde and MacMillan’s imidazolidinones one can rationalize why only strong electrophiles, such as stabilized carbenium ions (–8 < E < –2) or hexachlorocyclohexadienone (E = –6.75), are suitable electrophiles for enamine activated reactions with imidazolidinones. Several mechanistic controversies concerning iminium and enamine activated reactions could thus be settled by studying the reactivities of independently synthesized intermediates.Kinetic investigations of the reactions of N-heterocyclic carbenes (NHCs) with benzhydrylium ions showed that they have similar nucleophilicities to common organocatalysts (e.g., PPh3, DMAP, DABCO) but are much stronger (100–200 kJ mol–1) Lewis bases. While structurally analogous imidazolylidenes and imidazolidinylidenes have comparable nucleophilicities and Lewis basicities, the corresponding deoxy Breslow intermediates differ dramatically in reactivity. The thousand-fold higher nucleophilicity of 2-benzylidene-imidazoline relative to 2-benzylidene-imidazolidine is explained by the gain of aromaticity during electrophilic additions to the imidazoline derivatives. O-Methylated Breslow intermediates are a hundred-fold less nucleophilic than deoxy Breslow intermediates.

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“…A practical and robust way to prepare alkylated alcohols, aldehydes, or acids is to use the methodology developed by Evans that relies on the use of oxazolidinone chiral auxiliaries . Recently, we turned our attention towards the organocatalytic alkylation of aldehydes, which proceeds via an S N 1‐type mechanism, during which carbenium ions are generated from a precursor such as alcohols, or can be introduced as stable carbenium ions . We used the Mayr scale of reactivity extensively as a guide in order to choose suitable precursors of these stable carbenium ions (Fig.…”

Section: Introductionmentioning

confidence: 99%

“…20 Recently, we turned our attention towards the organocatalytic alkylation of aldehydes, which proceeds via an S N 1-type mechanism, 21 during which carbenium ions are generated from a precursor such as alcohols, or can be introduced as stable carbenium ions. [22][23][24][25][26] We used the Mayr scale of reactivity extensively as a guide in order to choose suitable precursors of these stable carbenium ions ( Fig. 1).…”

Section: Introductionmentioning

confidence: 99%

A Practical and Stereoselective Organocatalytic Alkylation of Aldehydes with Benzodithiolylium Tetrafluoroborate

et al. 2014

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Recently, the direct substitution of allylic, benzylic, and tertiary alcohols has been achieved via SN 1-type reactions with catalytic amounts of Brønsted or Lewis acids. When a new stereogenic center is formed most of these transformations produce the desired product as a racemate, as these reactions proceed through carbenium ions. The arsenal of activation modes available in organocatalysis can be used to set up suitable reaction conditions in which chiral nucleophiles (enamine catalysis) or chiral electrophiles (iminium catalysis, chiral counterion catalysis) can easily be generated. Recently, we have used stabilized carbenium ions, directly available or obtained from the corresponding alcohols, in new organocatalytic stereoselective SN 1-type reactions. The commercially available carbenium ion benzodithiolylium tetrafluoroborate can be used for the straightforward organocatalytic stereoselective alkylation of aldehydes. In this account we will illustrate the application of this methodology in the total synthesis of natural products and the preparation of valuable starting materials.

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Organocatalytic Stereoselective α‐Alkylation of Aldehydes with Stable Carbocations

Cited by 104 publications

References 81 publications

From QCA (Quantum Cellular Automata) to Organocatalytic Reactions with Stabilized Carbenium Ions

From QCA (Quantum Cellular Automata) to Organocatalytic Reactions with Stabilized Carbenium Ions

A quantitative approach to nucleophilic organocatalysis

A Practical and Stereoselective Organocatalytic Alkylation of Aldehydes with Benzodithiolylium Tetrafluoroborate

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