* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Download Orbitals - drjosephryan.com
Metal carbonyl wikipedia , lookup
Fischer–Tropsch process wikipedia , lookup
Marcus theory wikipedia , lookup
Enantioselective synthesis wikipedia , lookup
Kinetic resolution wikipedia , lookup
Physical organic chemistry wikipedia , lookup
Woodward–Hoffmann rules wikipedia , lookup
Elias James Corey wikipedia , lookup
Ring-closing metathesis wikipedia , lookup
George S. Hammond wikipedia , lookup
Ene reaction wikipedia , lookup
Diels–Alder reaction wikipedia , lookup
Discodermolide wikipedia , lookup
Tiffeneau–Demjanov rearrangement wikipedia , lookup
Hofmann–Löffler reaction wikipedia , lookup
Wolff rearrangement wikipedia , lookup
1,3-Dipolar cycloaddition wikipedia , lookup
Stille reaction wikipedia , lookup
Petasis reaction wikipedia , lookup
Aldol reaction wikipedia , lookup
Nucleophilic acyl substitution wikipedia , lookup
Strychnine total synthesis wikipedia , lookup
Baylis–Hillman reaction wikipedia , lookup
Hydroformylation wikipedia , lookup
14.2 Preparing Aldehydes and Ketones Aldehydes from oxidation of primary alcohols using the DessMartin periodinane reagent Preparing Aldehydes and Ketones Aldehydes from reduction of carboxylic esters using diisobutylaluminum hydride (DIBAH) Preparing Aldehydes and Ketones Secondary alcohols are oxidized by variety of chromium-based reagents to give ketones Aryl ketones from Friedel-Crafts acylation reactions Nucleophilic Addition of Grignard and Hydride Reagents: Alcohol Formation Mechanism of Grignard Reaction Nucleophilic Addition of Grignard and Hydride Reagents: Alcohol Formation In an analogous manner the reaction of aldehydes and ketones with hydride reagents may be represented as proceeding through a nucleophilic addition of a hydride ion (:H–) to the C=O carbon • LiAlH4 and NaBH4 act as if they are donors of hydride ion 14.7 Nucleophilic Addition of Amines: Imine and Enamine Formation Primary amines, RNH2, add to aldehydes and ketones to yield imines, R2C=NR Secondary amines, R2NH, add similarly to yield enamines, R2N-CR=CR2 Nucleophilic Addition of Amines: Imine and Enamine Formation Imines are common biological intermediates where they are often called Schiff bases Nucleophilic Addition of Amines: Imine and Enamine Formation Imine and enamine formations reach maximum rate around pH = 4 to 5 • Slow at pH > 5 because there is insufficient H+ present in solution to protonate intermediate carbinolamine –OH to yield the better leaving group –OH2+ • Slow at pH < 4 because the basic amine nucleophile is protonated and initial nucleophilic addition cannot occur Worked Example 14.1 Predicting the Product of Reaction between a Ketone and an Amine Nucleophilic Addition of Alcohols: Acetal Formation Acetal and hemiacetal groups are common in carbohydrate chemistry • Glucose, a polyhydroxy aldehyde, undergoes intramolecular nucleophilic addition • Exists primarily as a cyclic hemiacetal 14.9 Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction Wittig reaction • Converts aldehydes and ketones into alkenes • Phosphorus ylide, R2C–P(C6H5)3, adds to aldehyde or + ketone to yield dipolar, alkoxide ion intermediate • Ylide (pronounced ill-id) is a neutral, dipolar compound with adjacent positive and negative charges • Also called a phosphorane and written in the resonance form R2C=P(C6H5)3 • Dipolar intermediate spontaneously decomposes through a four-membered ring to yield alkene and triphenylphosphine oxide, (Ph)3P=O • Wittig reaction results in replacement of carbonyl oxygen with R2C= group of original phosphorane Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction Wittig reaction mechanism Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction • Phosphorus ylides are prepared by SN2 reaction of primary and some secondary alkyl halides with triphenylphosphine, (Ph)3P, followed by treatment with base Nucleophilic Addition of Phosphorus Ylides: The Wittig Reaction Wittig reactions used commercially to synthesize numerous pharmaceuticals Worked Example 14.3 Synthesizing an Alkene Using a Wittig Reaction What carbonyl compound and what phosphorus ylide might you use to prepare 3-ethylpent-2-ene? Worked Example 14.3 Synthesizing an Alkene Using a Wittig Reaction Solution Biological Reductions Cannizzaro reaction is a nucleophilic acyl substitution reaction of aldehydes and ketones • • • OH¯ adds to aldehyde to give tetrahedral intermediate H:¯ ion is transferred to a second aldehyde The aldehyde accepting the H:¯ ion is reduced and the aldehyde transferring the H:¯ is oxidized Biological Reductions Cannizzaro reaction mechanism is analogous to biological reduction in living organisms by nicotinamide adenine dinucleotide, NADH • NADH donates H:¯ to aldehydes and ketones, similar to tetrahedral alkoxide intermediate in Cannizzaro reaction Conjugate Nucleophilic Addition to α,βUnsaturated Aldehydes and Ketones Conjugate addition occurs because the nucleophile can add to either one of two electrophilic carbons of the a,b-unsaturated aldehyde or ketone Conjugate Nucleophilic Addition to α,βUnsaturated Aldehydes and Ketones Conjugated double bond of a,b-unsaturated carbonyl is activated by carbonyl group of the aldehyde or ketone • C=C double bond is not activated for addition in absence of carbonyl group Conjugate Nucleophilic Addition to α,βUnsaturated Aldehydes and Ketones Primary and secondary amines add to a,b-unsaturated aldehydes and ketones to yield b-amino aldehydes and ketones • Both 1,2- and 1,4-addition occur • Additions are reversible • More stable conjugate addition product accumulates Conjugate Nucleophilic Addition to α,βUnsaturated Aldehydes and Ketones Conjugate addition of an alkyl or other organic group to an a,bunsaturated ketone (but not aldehyde) is a useful 1,4addition reaction Conjugate Nucleophilic Addition to α,βUnsaturated Aldehydes and Ketones Conjugate addition of alkyl groups to an a,b-unsaturated ketone (not aldehyde) is accomplished with a lithium diorganocopper reagent, R2CuLi (Gilman reagent) • Lithium diorganocopper reagent is prepared by reaction of 1 equivalent of copper(I) iodide and 2 equivalents of an organolithium reagent, RLi • Organolithium reagent is prepared by reaction of lithium metal with an organohalide Conjugate Nucleophilic Addition to α,βUnsaturated Aldehydes and Ketones Primary, secondary, and even tertiary alkyl groups undergo conjugate addition • Alkynyl groups react poorly • Grignard reagents and organolithium reagents normally give direct carbonyl addition to a,b-unsaturated ketones Worked Example 14.4 Using a Conjugate Addition Reaction How might you use a conjugate addition reaction to prepare 2-methyl-3-propylcyclopentanone? Worked Example 14.4 Using a Conjugate Addition Reaction Solution Spectroscopy of Aldehydes and Ketones Spectroscopy of Aldehydes and Ketones Aldehyde protons (RCHO) absorb near 10 d in the 1H NMR • Aldehyde proton shows spin-spin coupling with protons on the neighboring carbon, with coupling constant J ≈ 3 Hz • Hydrogens on carbon next to a carbonyl group are slightly deshielded and absorb near to 2.0 to 2.3 d Spectroscopy of Aldehydes and Ketones Carbonyl-group carbon atoms of aldehydes and ketones have characteristic 13C NMR resonances in the range of 190 to 215 d