"Straight-chain allylic alcohols have been crucial to the development of stereoselective syntheses of complex natural products since they can be converted stereoselectively into epoxides and via further elaboration of these into a host of functionalized compounds of predictable stereochemistry."

"Epoxides (oxiranes) are widely used as versatile synthetic intermediates because regio- and stereoselective methods exist both for their construction and subsequent reactions. Reactions of epoxides are dominated by the electrophilic nature of the strained three-membered ring, which is susceptible to attack by a variety of nucleophiles. … The reaction of alkenes with peroxy acids provides for convenient and selective oxidation of double bonds. … Epoxidation involves an electrophilic syn-addition of the oxygen moiety of the peroxy acid to the double bond. The concerted formation of two new C-O bonds ensures that the reaction is stereospecific: cis-alkenes furnish the corresponding cis-epoxides and trans-alkenes the corresponding trans-isomers (racemic)."

"Oxidation of α,β-unsaturated ketones with alkaline hydrogen peroxide produces the corresponding keto epoxides in good yields. This nucleophilic epoxidation proceeds via an initial Michael-type addition of the hydroperoxide anion to the enone system … Treatment of enones with basic tert-butyl hydroperoxide provides an alternative route for epoxidation of enones when the alkaline hydrogen peroxide procedure fails."

"Dirnethyldioxirane (DMDO) is a mild reagent for epoxidation under neutral conditions of electron-rich as well as of electron-deficient alkenes. Moreover, dimethyldioxirane is often the oxidant of choice for the preparation of labile epoxides. … Methyl(trifluoromethyl)dioxirane (TFDO), … is more reactive than DMDO by a factor of ~600. … TFDO can be used to regioselectively oxidize tertiary over secondary C-H bonds via an “oxenoid” (butterfly) mechanism."

"The reaction of chloro- or bromohydrins with bases provides an economical route for the preparation of epoxides. Halohydrins are readily accessible by treatment of an alkene with either hypochlorous acid (Cl2 + H2O → HOCl), hypochlorite bleach solution (NaOCl), or hypobromous acid (NBS + H2O → HOBr). These reactions involve the initial formation of a halohydrin via anti-addition of X+ and HO-, followed by internal "SN2" displacement of the halide by the oxyanion."

"Chloroiodomethane on treatment with methyllithium-lithium bromide or n-butyllithium at low temperature undergoes lithium iodide exchange to form a lithium chlorocarbenoid species [LiCH2Cl]. This highly reactive "carbanion" intermediate can be intercepted by the carbonyl group of aldehydes or ketones before it undergoes α-elimination to generate carbene and LiC1. Displacement of chloride from the initially formed carbonyl adducts furnishes the corresponding epoxides in high yields."

"The inherent strain (-27 kcal/mol) of epoxides makes them prone to (1) ring opening by a wide range of nucleophiles, (2) base-induced rearrangement, and (3) acid-catalyzed isomerization. … Generally, nucleophilic opening of an unsymmetrically substituted epoxide is regioselective. … . In cyclohexane derivatives, opening of the epoxide ring with nucleophilic reagents proceeds stereospecifically in the majority of cases via an S,2 reaction, placing the oxygen of the epoxide and the attacking nucleophile in a trans- and diaxial-relationship. Thus, a single diastereomer of an epoxide gives upon ring opening a single diastereomer of the product."

"Although epoxidation of cyclic alkenes occurs preferentially from the less hindered side, the presence of a polar substituent near the double bond may reverse the facial direction of attack by the peroxide."

"Many oxidants transform acyloins (α-hydroxy ketones) into α-diketones. Copper and bismuth oxidants are commonly selected for this transformation. … Cu(II) salts (e.g., Cu(OAc), or CuSO4) in stoichiometric amounts convert acyloins into diketones. Catalytic amounts of cupric acetate can be used in conjunction with ammonium nitrate. … Commercially available Bi2O3, in the presence of acetic acid, oxidizes acyloins to α-diketones in good yields."

"The question of how one chooses appropriate carbon-carbon bond disconnections is related to functional group manipulations since the distribution of formal charges in the carbon skeleton is determined by the functional group(s) present. The presence of a heteroatom in a molecule imparts a pattern of electrophilicity and nucleophilicity to the atoms of the molecule. The concept of alternating polarities or-latent polarities (imaginary charges) often enables one to identify the best positions to make a disconnection within a complex molecule. Functional groups may be classified as follows: E class: Groups conferring electrophilic character to the attached carbon (+) … G class: Groups conferring nucleophilic character to the attached carbon (-) … A class: Functional groups that exhibit ambivalent character (+ or -) … The positive charge (+) is placed at the carbon attached to an E class functional group … and the TM is then analyzed for consonant and dissonant patterns by assigning alternating polarities to the remaining carbons. In a consonant pattern, carbon atoms with the same class of functional groups have matching polarities, whereas in a dissonant pattern, their polarities are unlike. If a consonant pattern is present in a molecule, a simple synthesis may often be achieved."

"The structural features that make it possible to classify compounds into families are called functional groups. ... The chemistry of every organic molecule, regardless of size and complexity, is determined by the functional groups it contains."

"The most striking characteristic of thiols is their appalling odor. Skunk scent, for instance, is caused primarily by the simple thiols 3-methyl-1-butanethiol and 2-butene-1-thiol. Volatile thiols such as ethanethiol are also added to natural gas and liquefied propane to serve as an easily detectable warning in case of leaks."

"Diethyl ether and other simple symmetrical ethers are prepared industrially by the sulfuric acid–catalyzed reaction of alcohols."

"Ethers are relatively stable and unreactive in many respects, but some ethers react slowly with the oxygen in air to give peroxides, compounds that contain an O – O bond. The peroxides from low-molecular-weight ethers such as diisopropyl ether and tetrahydrofuran are explosive and extremely dangerous, even in tiny amounts. Ethers are very useful as solvents in the laboratory, but they must always be used cautiously and should not be stored for long periods of time."

"Thiols can be oxidized by Br2 or I2 to yield disulfides (RSSR′). The reaction is easily reversed, and a disulfide can be reduced back to a thiol by treatment with zinc and acid."

"The most generally useful method of preparing ethers is by the Williamson ether synthesis, in which an alkoxide ion reacts with a primary alkyl halide or tosylate in an SN2 reaction."

"In the NMR spectra of aldehydes and ketones, the formyl hydrogens and the carbonyl carbons show strong deshielding. The carbon – oxygen double bond in ketones gives rise to a strong infrared band at about 1715cm-1, which is shifted to lower frequency by conjugation and to higher frequency in aldehydes and small rings. The ability of nonbonding electrons to be excited into the π* molecular orbitals causes the carbonyl group to exhibit characteristic, relatively long-wavelength UV absorptions. Finally, aldehydes and ketones fragment in the mass spectrometer by α cleavage and McLafferty rearrangement."

"In the enolate ion, the inductive effect of the positively polarized carbonyl carbon strongly stabilizes the negative charge at the a-position. Aldehydes are stronger acids than ketones because their carbonyl carbon bears a larger partial positive charge (...) Further strong stabilization is provided by delocalization of charge onto the electronegative oxygen, as described by the resonance forms just pictured. The effect of delocalization is also refl ected in the electrostatic potential map of the acetone enolate shown in the margin (on an attenuated scale), which exhibits negative charge (red) on the a-carbon as well as on the oxygen. An example of enolate formation is the deprotonation of cyclohexanone by lithium diisopropylamide (LDA; Section 7-8)."

"The hydrogens on the carbon next to the carbonyl group in aldehydes and ketones are acidic, with pKa values ranging from 16 to 21. Deprotonation leads to the corresponding enolate ions, which may attack electrophilic reagents at either oxygen or carbon. Protonation at oxygen gives enols."

"The dipolar Lewis structure indicates the polarization of the C=O bond. Even though it is a minor contributor (because of the lack of an octet on carbon), it explains the deshielding of the carbonyl carbon. In carboxylic acids, however, the corresponding dipolar form contributes less to the resonance hybrid: The hydroxy oxygen can donate an electron pair to give a third arrangement in which the carbon and both oxygen atoms have octets. The degree of positive charge on the carbonyl carbon and therefore its deshielding are greatly reduced. The changes in electron density distribution around the carbonyl function when going from acetone to acetic acid are shown in their respective electrostatic potential maps."

"Carboxylic acids are useful reagents and synthetic precursors. The two simplest ones are manufactured on a large scale industrially. Formic acid is employed in the tanning process in the manufacture of leather and in the preparation of latex rubber. It is synthesized effi ciently by the reaction of powdered sodium hydroxide with carbon monoxide under pres sure. This transformation proceeds by nucleophilic addition followed by protonation."

"Many of the oxidants employed to prepare aldehydes from primary alcohols may be used to further oxidize the aldehyde initially formed to the corresponding carboxylic acid. The most common oxidants for this purpose include KMnO4, chromic acid, sodium chlorite, silver oxide, and PDC in DMF."

"Carboxylic acids react with alcohols to form esters, as long as a mineral acid catalyst is present. This reaction is only slightly exothermic, and its equilibrium may be shifted in either direction by the choice of reaction conditions. The reverse of ester formation is ester hydrolysis. The mechanism of esterifi cation is acid-catalyzed addition of alcohol to the carbonyl group followed by acid-catalyzed dehydration. Intramolecular ester formation results in lactones, favored only when five- or six-membered rings are produced."

"α,β-Unsaturated aldehydes are converted directly to carboxylate esters by MnO2 and NaCN in an alcohol solvent. Sodium cyanide catalyzes the oxidation by forming a cyanohydrin that is susceptible to MnO2 oxidation. Methanolysis of the acyl cyanide intermediate in the example below gives the methyl ester in excellent yield. The oxidation of allylic alcohols directly to methyl carboxylates has been reported using MnO2 and sodium cyanide in methanol. Aldehydes dissolved in alcohols react with 1 to 2 equivalents of aqueous NaOCl or Oxone (a potassium triple-salt that contains potassium peroxymonosulfate, KHSO5) to furnish the corresponding esters."

"Acyl chlorides are attacked by a variety of nucleophiles, the reactions leading to new carboxylic acid derivatives, ketones, and aldehydes by addition – elimination mechanisms. The reactivity of acyl halides makes them useful synthetic relay points on the way to other carbonyl derivatives."

"Although the chemistry of carboxylic anhydrides is very similar to that of acyl halides, anhydrides have some practical advantages. Acyl halides are so reactive that they are difficult to store for extended periods without some hydrolysis occurring due to exposure to atmospheric moisture. As a result, chemists usually prepare acyl halides immediately before they are to be used. Anhydrides, being slightly less reactive toward nucleophiles, are more stable, and several (including all the examples illustrated in this section) are commercially available. Consequently, carboxylic anhydrides are often the preferred reagents for the preparation of many carboxylic acid derivatives."

"The amides are the least reactive of the carboxylic acid derivatives, in part because they are strongly stabilized by delocalization of the nitrogen lone pair (...) As a consequence, their nucleophilic addition – eliminations require relatively harsh conditions. For example, hydrolysis to the corresponding carboxylic acid occurs only upon prolonged heating in strong aqueous acid or base by addition – elimination mechanisms. Acid hydrolysis liberates the amine in the form of an ammonium salt."

"In contrast to carboxylic acids and esters, the reaction of amides with lithium aluminum hydride produces amines instead of alcohols. (...) The mechanism of reduction begins with hydride addition, which gives a tetrahedral intermediate. Elimination of an aluminum alkoxide leads to an iminium ion.Addition of a second hydride gives the final amine product. (...) Reduction of amides by bis(2-methylpropyl)aluminum hydride (diisobutylaluminum hydride) furnishes aldehydes."

"Amines adopt an approximately tetrahedral structure in which the lone electron pair occupies one vertex of the tetrahedron. They can, in principle, be chiral at nitrogen but are difficult to maintain in enantiomerically pure form because of fast inversion at the nitrogen. Amines have boiling points higher than those of alkanes of similar size. Their boiling points are lower than those of the analogous alcohols because of weaker hydrogen bonding, and their water solubility is between that of comparable alkanes and alcohols."

"Benzylic oxidations of alkyl groups take place in the presence of permanganate or chromate; benzylic alcohols are converted into the corresponding ketones by manganese dioxide. The benzylic ether function can be cleaved by hydrogenolysis in a transformation that allows the phenylmethyl (benzyl) substituent to be used as a protecting group for the hydroxy function in alcohols."

"The in situ generation of an iminium ion from a carbonyl compound lowers the LUMO energy of the system. Iminium catalysis is comparable to Brønsted- or Lewis acid activation of carbonyl compounds. The LUMO energy is lowered, theα-CH acidity increases, and nucleophilic additions including conjugate additions as well as pericyclic reactions are facilitated."

"Having seen a variety of types of Claisen condensations, we can now ask how this process may be logically analyzed for synthetic use. Three facts are available to help us: (1) Claisen condensations always form 1,3-dicarbonyl compounds; (2) one of the reaction partners in a Claisen condensation must be an ester, whose alkoxide group is lost in the course of the condensation; and (3) the other reaction partner (the source of the nucleophilic enolate) must contain at least two acidic hydrogens on an a-carbon. In addition, if a mixed condensation is being considered, one reaction partner should be incapable of self-condensation (e.g., it should lack α-hydrogens). If we are given the structure of a target molecule and wish to determine whether (and, if so, how) it can be made by a Claisen condensation, we must analyze it retrosynthetically with the preceding points in mind. For example, let us consider whether 2-benzoylcyclohexanone can be made by a Claisen condensation."

"An alkene, sometimes called an olefin, is a hydrocarbon that contains a carbon– carbon double bond. Alkenes occur abundantly in nature. … Ethylene and propylene, the simplest alkenes, are the two most important organic chemicals produced industrially. Approximately 127 million metric tons of ethylene and 54 million metric tons of propylene are produced worldwide each year for use in the synthesis of polyethylene, polypropylene, ethylene glycol, acetic acid, acetaldehyde, and a host of other substances."

"Reaction of the stabilized anions derived from β-dicarbonyl compounds and related analogs with α,β-unsaturated carbonyl compounds leads to 1,4-additions. This trans formation, an example of Michael addition, is base-catalyzed and works with α,β-unsaturated ketones, aldehydes, nitriles, and carboxylic acid derivatives, all of which are termed Michael acceptors. (...) β-Dicarbonyl anions, like ordinary enolate anions, undergo Michael additions to α,β-unsaturated carbonyl compounds. Addition of a β-ketoester to an enone gives a diketone, which can generate six-membered rings by intramolecular aldol condensation (Robinson annulation)."

"In organic synthesis, the carbonyl group is intimately involved in many reactions that create new carbon-carbon bonds. The carbonyl group is electrophilic at the carbon atom and hence is susceptible to attack by nucleophilic reagents. Thus, the carbonyl group reacts as a formyl cation or as an acyl cation. A reversal of the positive polarity of the carbonyl group so it acts as a forrnyl or acyl anion would be synthetically very attractive. To achieve this, the carbonyl group is converted to a derivative whose carbon atom has the negative polarity. After its reaction with an electrophilic reagent, the carbonyl is regenerated. Reversal of polarity of a carbonyl group has been explored and systematized by Seebach."

"In conclusion, it is obvious that N-heterocyclic carbenes and their unique, but concurrently versatile reactivity have already proven wide applicability. The offered catalytic (and enantioselective) access to important reactive intermediates suchas homoenolates or enolates as well as their additional catalytic properties will smooth the way for mild and sustainable synthesis of multifunctionalized compounds."

"β-Dicarbonyl compounds such as ethyl 3-oxobutanoate (acetoacetate) and diethyl propanedioate (malonate) are versatile synthetic building blocks for elaborating more complex molecules. Their unusual acidity makes it easy to form the corresponding anions, which can be used in nucleophilic displacement reactions with a wide variety of substrates. Their hydrolysis produces 3-ketoacids that are unstable and undergo decarboxylation on heating."

"Because of its double bond, an alkene has fewer hydrogens than an alkane with the same number of carbons … and is therefore referred to as unsaturated. Knowing this relationship, it’s possible to work backward from a molecular formula to calculate a molecule’s degree of unsaturation — the number of rings and/or multiple bonds present in the molecule. … The unknown therefore contains two double bonds, one ring and one double bond, two rings, or one triple bond. There’s still a long way to go to establish structure, but the simple calculation has told us a lot about the molecule. … Add the number of halogens to the number of hydrogens. … Ignore the number of oxygens. … Subtract the number of nitrogens from the number of hydrogens."

"The double bond in alkenes, such as ethene (ethylene), and the triple bond in alkynes, such as ethyne (acetylene), are the result of the ability of the atomic orbitals of carbon to adopt sp2 and sp hybridization, respectively."

"The carbon–carbon double bond in alkenes has special electronic and structural features. This section reviews the hybridization of the carbon atoms in this functional group, the nature of its two bonds (s and p), and their relative strengths."

"Alkenes possessing allylic C-H bonds are oxidized by SeO2 either to allylic alcohols or esters or to α,β-unsaturated aldehydes or ketones, depending on the experimental conditions. … Reaction of chromic anhydride (CrO2) with t-butanol yields t-butyl hydrogen chro- mate, a powerful oxidant suitable for allylic oxidation of electron-deficient alkenene. Copper(I) salts catalyze thc allylic oxidation of alkenes in the presence of peresters, such as tert-BuO2COPh, to afford the corresponding allylic benzoate esters."

"The characteristic hybridization scheme for the triple bond of an alkyne controls its physical and electronic features. It is responsible for strong bonds, the linear structure, and the relatively acidic alkynyl hydrogen. In addition, alkynes are highly energetic compounds. Internal isomers are more stable than terminal ones, as shown by the relative heats of hydrogenation."

"The cylindrical π cloud around the carbon – carbon triple bond induces local magnetic fields that lead to NMR chemical shifts for alkynyl hydrogens at higher fields than those of alkenyl protons. Long-range coupling is observed through the C≡C linkage. Infrared spectroscopy provides a useful complement to NMR data, displaying characteristic bands for the C≡C and ≡C–H bonds of terminal alkynes. In the mass spectrometer, alkynes fragment to give resonance-stabilized cations."

"Conversion of 1-alkynes into substituted actic acids without the loss of one carbon is accomplished via hydroboration-oxidation … Ruthenium- or permanganate-mediated oxidations of internal alkynes are highly dependent on solvent conditions and generally afford the corresponding α-diketones."

"Allylic radicals, cations, and anions are unusually stable. In Lewis terms, this stabilization is readily explained by electron delocalization. In a molecular-orbital description, the three interacting p orbitals form three new molecular orbitals: One is considerably lower in energy than the p level, another one stays the same, and a third is higher in energy."

"A consequence of delocalization is that resonance-stabilized allylic intermediates can readily participate in reactions of unsaturated molecules. (...) These conditions slow the ionic addition pathway sufficiently to allow a faster radical chain mechanism to take over, leading to radical allylic substitution."

"Conjugated dienes are electron rich and are attacked by electrophiles to give intermediate allylic cations on the way to 1,2- and 1,4-addition products. These reactions may be subject to kinetic control at relatively low temperatures. At relatively higher temperatures, the kinetic product ratios may change to thermodynamic product ratios, when such product formation is reversible."

"Aldehydes and ketones are among the most important of all functional groups, both in the chemical industry and in biological pathways. ... Aldehydes are normally prepared in the laboratory by oxidation of primary alcohols or by partial reduction of esters."

"In conclusion, the conjugate umpolung of α,β-unsaturated aldehydes represents a versatile and powerful method to synthesize different cyclic products such as β- and γ-lactones and cyclopentenes. More valuable applications based on the NHC-catalyzed umpolung are expected to be discovered in due course."

"The carbonyl group in aldehydes and ketones is an oxygen analog of the carbon–carbon double bond. However, the electronegativity of oxygen polarizes the pbond, thereby rendering the acyl substituent electron withdrawing. The arrangement of bonds around the carbon and oxygen is planar, a consequence of sp2 hybridization."