Organic Reaction Mechanisms 2008

An annual survey covering the literature dated January to December 2008

A. C. Knipe

• Publisher: Wiley
• Year: 2011
• ISBN:
  9781119956884
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Organic Chemistry

This volume is the 44th in this classical series. In every volume relevant reaction mechanisms are featured in chapters entitled:

• Reaction of Aldehydes and Ketones and their Derivatives
• Reactions of Carboxylic, Phosphoric, and Sulfonic Acids and their Derivatives
• Oxidation and Reduction
• Carbenes and Nitrenes
• Nucleophilic Aromatic Substitution
• Electrophilic Aromatic Substitution
• Carbocations
• Nucleophilic Aliphatic Substitution
• Carbanions and Electrophilic Aliphatic Substitution
• Elimination Reactions
• Addition Reactions: Polar Addition
• Addition Reactions: Cycloadditions
• Molecular Rearrangements

An experienced team of authors is compiling these reviews every year, so that the reader can rely on a continuing quality of selection and presentation. As a new service to the reader all reaction mechanisms leading to stereospecific products are highlighted. This reflects the needs of the organic synthetic community with leads to chiral reactions.

Detailed author and subject indexes help the reader to find the information they are looking for.

As a new service to the reader all mechanisms featuring 'Enantiospecific and diastereospecific' reactions are highlighted. This reflects the interest of synthetic organic chemists in such reactions and the pharmaceutical role of chiral molecules.

CHAPTER 1

Reactions of Aldehydes and Ketones and their Derivatives

A. C. KNIPE

Faculty of Life and Health Sciences, University of Ulster, Coleraine

Formation and Reactions of Acetals and Related Species

Reactions of Glucosides and Nucleosides

Formation and Reactions of Nitrogen Derivatives

Imines: Synthesis, Tautomerism, Catalysis

The Mannich and Nitro-Mannich Reactions

Addition of Organometallics

Oxidation and Reduction of Imines

Iminium Species

Imine Cycloadditions

Other Reactions of Imines

Oximes, Hydrazones, and Related Species

C–C Bond Formation and Fission: Aldol and Related Reactions

Regio-, Enantio-, and Diastereo-selective Aldol Reactions

Intramolecular Aldols

Mukaiyama and Vinylogous Aldols

Nitrile/Nitro/Nitroso Aldols

Other Aldol-type Reactions

Pinacol- and Benzoin-type Coupling

The Baylis-Hillman and its Aza and Morita Variants

Allylation and Related Reactions

Alkynations

Michael Additions

Other Addition Reactions

General and Theoretical

Addition of Organozincs

Addition of Other Organometallics

Grignard-type Reactions

Hydrocyanation and Cyanosilylation

Hydrosilylation and Hydrophosphonylation

Miscellaneous Additions

Enolization and Related Reactions

Oxidation and Reduction of Carbonyl Compounds

Regio-, Enantio-, and Diastereo-selective Reduction Reactions

Oxidation Reactions

Other Reactions

References

Formation and Reactions of Acetals and Related Species

A water-soluble self-assembled host molecule [Ga₄L₆]¹²⁻ has been found to catalyse the hydrolysis of orthoformates HC(OR)₃ in basic solution with marked rate accelerations of up to 3900 (R = Pr) relative to the uncatalysed reaction.¹ Enzyme-like Michaelis-Menten kinetics apply and ¹³C labeling experiments have helped to establish that the neutral substrate is encapsulated in the host in the resting state; this is consistent with the more negative entropy of activation found for the catalytic process. The solvent isotope effects k;(H₂O)/k(D₂O) = 1.6 is indicative of an A-S_E2 mechanism with rate-limiting proton transfer, in contrast with the A1 mechanism, for the catalysed reaction which involves rate-limiting decomposition of the protonated substrate.

Pyridinium salt derivatives have been found to catalyse (at 0.1% loading) acetalization reactions of both aldehydes and ketones in methanol at room temperature more efficiently than Brønsted acids of pK_a = 22.²

A study of the effects of the strength of the nucleophile (Nu-SiMe₃) on the stereochemical outcome of substitution reactions of cyclic acetals (in CH₂Cl₂ in the presence of Me₃SiOTf or BF₃OEt₂) has revealed a continuum of mechanisms. Stereoselective S_N1 mechanisms (via the oxocarbenium ion intermediate) occur with weak and moderate nucleophiles and poor leaving groups, whereas strong nucleophiles adopt unselective diffusion-limited S_Nl and S_N2 pathways.³

A highly enantioselective (up to 99% ee) and diastereoselective aldol-type reaction of β-keto esters with acetals has been achieved under the catalytic influence of chiral cationic Pd(II)-and Pt(II)-binap complexes which can act as acid/base catalysts, with simultaneous activation of both the nucleophile (as chiral metal enolate) and acetal;⁴the enantioselectivity is apparently dependent on conversion of the acetal into the oxonium ion, by protonation under the acidic conditions used.

A Lewis base-catalysed diastereoselective and enantioselective glycolate aldol reaction has been developed whereby a range of aldehydes can be converted to both syn-and anti-1,2-diols under the same catalytic system by adjusting the size of the silyl ketene acetal

used as the nucleophilic component; these Mukaiyama-type aldol reactions are conducted In CH₂Cl₂ at −78°C in the presence of SiCl₄, i-Pr₂NEt and a bisphosphoramide catalyst.⁵

The Brønsted acid catalysed aza-Ferrier reaction of N-Boc-2-(l,3-dienyloxy) pyrrolidines has been found to proceed via heterolytic C–O cleavage to give the iminium alkoxlde, from which the corresponding α-(N-Boc-2-pyrrolidinyl)aldehyde is formed in excellent yield and high α-regioselectivity by C–C bond formation.⁶

Reactions of Glucosides and Nucleosides

Nucleophilic substitution reactions of 2-phenylthio-substituted carbohydrate acetals and related systems have been reviewed, with particular reference to episulfonium ions vs oxocarbenium ions as reactive intermediates in stereocontrolled glycosylation reactions.⁷

Mechanistic study (using kinetic experiments, Hammet plots, DFT calculations and ¹¹B NMR) of regioselective borane reductive openings of cyclic acetals has established that the outcome depends on the electrophile with which the more electron-rich oxygen associates, and this can be altered by Lewis acid activation of the borane.⁸

A plausible mechanism has been suggested to account for α-selective glucosylation which allowed the synthesis of the tetrasaccharide [Glcα1 → 2Glcα1 → 3Glcα1 → 3Man], enabled by the synergistic effect of combined etheral and halogenic solvents.⁹

Hydrolysis of toxic 7-hydroxycoumarin glucosides and other aryl and alkyl glucosides catalysed by modified α- and β-cyclodextrin dicyanohydrins has been found to follow Michaelis-Menten kinetics and to display rate increases of up to k_cat/k_uncat = 7569 (for the hydroxycoumarin glucoside).¹⁰

Results of a DFT study of suitable analogues have explained the relative O(3)/O(4) reactivities previously reported for reaction of glycosyl donors with both α- and β-methyl glycosides of N-dimethyrmaleoyl (DMM) glucosamine acceptors protected at O(6).¹¹ The preferential or exclusive substitution at O(3) for the α-anomers and at O(4) for the β-anomers has been attributed to the different alignments for the DMM ring: for the β-anomers the ring is parallel to the C(2)–H(2) bond for steric reasons, whereas for the α-anomers it is tilted such that a strong hydrogen bond between one of its carbonyl groups and HO(3) makes O(3) more reactive.

A study of potential neighbouring group participation by non-vicinal esters in glycosylation reactions has found that glycopyranosylation Is aided by intermediate formation of a 1,3-O-cyclic carbonate ester, with loss of a t-butyl cation from a t-butoxycarbonyl ester group axially substituted at C(3), but that the corresponding 3-O-equatorial, 4-O-axial and -equatorial, and 6-O carbonates do not undergo intramolecular reaction under typical glycosylation conditions.¹² Galactopyranosylation reactions of a 4-O-(2-carboxy)benzoate ester and a 4-O-(4-methoxybenzoate) ester also failed to exhibit neighbouring group participation; this was particularly clear for the latter, for which ¹⁸O quenching failed to detect bridging intermediates. The unesterified hydroxyl groups were protected as benzyl ethers.

Formation and Reactions of Nitrogen Derivatives

Imines: Synthesis, Tautomerism, Catalysis

Isomerization of the imine derived from benzylamine an...

Table of contents

• Cover
• Title page
• Copyright page
• Contributors
• Preface
• 1. Reactions of Aldehydes and Ketones and their Derivativesby A. C. Knipe
• 2. Reactions of Carboxylic, Phosphoric, and Sulfonic Acids and their Derivatives by C. T. Bedford
• 3. Oxidation and Reduction by K. K. Banerji
• 4. Carbenes and Nitrenes by M. G. Moloney
• 5. Nucleophilic Aromatic Substitution byM. R. Crampton
• 6. Electrophilic Aromatic Substitution by R. G. Coombes
• 7. Carbocations by R. A. McClelland
• 8. Nucleophilic Aliphatic Substitution by A. C. Knipe
• 9. Carbanions and Electrophilic Aliphatic Substitution by M. L. Birsa
• 10. Elimination Reactions by M. L. Birsa
• 11. Addition Reactions: Polar Addition by P. Kočovský
• 12. Addition Reactions: Cycloaddition by N. Dennis
• 13. Molecular Rearrangements: Part 1. Pericyclic Molecular Rearrangements by S. K. Armstrong
• 14. Molecular Rearrangements: Part 2. Other Reactions by A. Brandi and M. Gensini
• Author Index
• Subject Index