18 Four Carbon—Heteroatom Bonds: X—C≡X, X=C=X, X2C=X, CX4
Knight, J. G., Science of Synthesis, (2005) 18, 1.
This volume covers the synthesis of compounds containing four carbon—heteroatom bonds. These are shown in Table 1 together with the sections in which they appear.
Table 1 Structures and Nomenclature of the Four Carbon—Heteroatom Bond Containing Compounds Covered in Volume 18
Product Class | Structural Formula(e) | Section |
---|---|---|
cyanogen halides, cyanates and their sulfur, selenium, and tellurium analogues, sulfinyl and sulfonyl cyanides, cyanamides, and phosphaalkynes | XC≡N, XC≡P (X = halo, OR1, SR1, SeR1, TeR1, NR1R2) | 18.1 |
carbon dioxide, carbonyl sulfide, carbon disulfide, isocyanates, isothiocyanates, carbodiimides, and their selenium, tellurium, and phosphorus analogues | X=C=Y (X, Y = O, S, Se, Te, NR1, PR1) | 18.2 |
carbonic acid halides | XC(O)Y (X = halo; Y = halo, OR1, SR1, SeR1, NR1R2, PR1R2) | 18.3 |
carbonic acids and esters, and their sulfur, selenium, and tellurium analogues | XC(O)Y (X, Y = OR1, SR1, SeR1, TeR1) | 18.4 |
polymeric carbonic acids and esters, and their sulfur analogues | polymers based on XC(O)Y (X = Y = OR1, SR1) | 18.5 |
carbamic acids and esters, and their sulfur, selenium, tellurium, and phosphorus analogues | XC(O)NR1R2, XC(O)PR1R2 (X = OR3, SR3, SeR3, TeR3) | 18.6 |
polymeric carbamic acids and esters, and their sulfur analogues | polymers based on XC(O)NR1R2 (X = OR3, SR3) | 18.7 |
ureas | R1R2NC(O)NR3R4 | 18.8 |
polymeric ureas | polymers based on R1R2NC(O)NR3R4 | 18.9 |
thiocarbonic acids and thiocarbamic acids and esters, ureas, and their sulfur, selenium, tellurium, and phosphorus analogues | XC(S)Y (X, Y = halo, OR1, SR1, SeR1, TeR1, NR1R2, PR1R2) | 18.10 |
seleno- and tellurocarbonic acids and derivatives | XC(Se)Y, XC(Te)Y (X, Y = halo, OR1, SR1, SeR1, TeR1, NR1R2, PR1R2) | 18.11 |
imidic acids, isoureas, and their sulfur, selenium, and phosphorus analogues | XC(=NR1)Y, XC(=PR1)Y (X, Y = halo, O, SR2, SeR2, TeR2, NR2R3, PR2R3) | 18.12 |
guanidines | R1R2NC(=NR3)NR4R5 | 18.13 |
phosphorus analogues of guanidine | XC(=NR3)PR1R2, XC(=PR1)Y (X, Y = NR1R2, PR1R2) | 18.14 |
tetraheterosubstituted methanes with a carbon—halogen bond | XCY3 (X = halo; Y = halo, OR1, SR1, SeR1, TeR1, NR1R2, PR1R2) | 18.15 |
other tetraheterosubstituted methanes | CX4 (X = OR1, SR1, SeR1, TeR1, NR1R2, PR1R2) | 18.16 |
References to reviews on these specific functional groups are given in each section. Discussions of each specific group are generally subdivided into methods that have been selected as the most useful for the preparation of the product class in question. Where possible, each method is presented separately as follows:
1. Introduction: comparison with other methods.
2. Presentation of the scope of the method to include background, discussion of representative examples, safety; mechanistic information where relevant to the use of the method in synthesis; a table of examples (for selected methods); reaction schemes.
3. Representative experimental procedures.
In some cases, methods are further subdivided into variations on a method, each variation being presented according to the above format. The coverage is not exhaustive, rather the most useful and reliable methods for the synthesis of each functional group have been selected. In some cases, methods that are recommended for limited use, or that have not yet been fully developed, are listed at the end of a section for reference. Tables and representative experimental procedures are given to illustrate the applicability of each approach.
This introduction will outline the individual product classes together with highlighted synthetic methods.
Section 18.1 covers compounds containing the XC≡N or XC≡P unit. Many of these are thermally and hydrolytically unstable toxic compounds. Cyanogen fluoride (FCN) is explosive and decomposes to give polymeric species at room temperature. In contrast, cyanogen bromide (BrCN) and chloride (ClCN) are commercially available. All of the cyanogen halides are electrophilic and react with both heteroatom and carbon nucleophiles. These reactions can be used to produce many of the other derivatives covered in Section 18.1; for example, reaction with alcohols leads to cyanates 1 (Scheme 1).[1–3]
Scheme 1 Cyanates by Alcoholysis of Cyanogen Halides[1–3]
Because of the electronegativity of oxygen, cyanates (R1OCN) are more electrophilic than normal nitriles. Alkyl cyanates rearrange to the more thermodynamically stable isocyanates (R1NCO).[2] Alkyl thiocyanates (R1SCN) rearrange in a similar way, but are thermally and hydrolytically more stable than the corresponding cyanates. In contrast, seleno- and especially tellurocyanates are more labile and difficult to handle due to the weakness of the C—Se or C—Te bond.
Sulfonyl cyanides 2 may be obtained by oxidation of thiocyanates,[4] but the method of choice is nucleophilic substitution of a cyanogen halide by a sulfinate anion 3 (Scheme 2).[5] Sulfonyl cyanides have similar electrophilicity to cyanogen halides but are less volatile, less toxic, and easier to handle. They can be used to transfer the cyano group to a host of nucleophiles such as thiols, alcohols, amines, and carbon nucleophiles such as enolates and organometallic species.[6]
Scheme 2 Synthesis of Sulfonyl Cyanides[4,5]
Cyanamide itself (H2NCN) is highly toxic and polymerizes violently above its melting point. Monosubstituted cyanamides (R1HNCN) may act as either nucleophiles or electrophiles, as indicated by the resonance forms in Scheme 3. They are commonly used as precursors to a range of other classes of compound found in this volume (ureas, carbamates, guanidines, and related heterocycles).[7–10]
Scheme 3 Resonance Forms of Cyanamides
The most commonly used cyanophosphonate is diethyl cyanophosphonate (4, diethyl phosphorocyanidate, DEPC), which is made by the Arbuzov reaction between triethyl phosphite and cyanogen bromide (Scheme 4).[11] Diethyl cyanophosphonate is used as a coupling reagent for acylation reactions, for example in peptide synthesis under mild conditions.[12]
Scheme 4 Arbuzov Reaction To Form Diethyl Cyanophosphonate[11]
Few heteroatom-substituted phosphaalkynes (XC≡P) have been reported. They are usually prepared, in low yield, by elimination reactions. The C≡P bond undergoes cycloaddition reactions to form phosphaheterocycles.
Heterocumulenes (X=C=Y) are the subject of Section 18.2. Due to removal of electron density from the central carbon by the electronegative atoms X and Y, these compounds are normally electrophilic at carbon and are susceptible to attack by a range of heteroatom and carbon nucleophiles. Attack by heteroatom nucleophiles typically gives rise to other classes of compound found in this volume (Scheme 5). They also undergo cycloaddition across one of the π-bonds, especially when reacting with π-systems which have some nucleophilic character.
Scheme 5 Nucleophilic Attack on Heterocumulenes
Supercritical carbon dioxide has become an important reaction medium for green chemistry.[13,14] Carbon disulfide is more reactive than carbon dioxide due to the C=S bonds being longer and having weaker π-overlap than the corresponding C=O bonds. The initial adducts of nucleophilic addition are also less prone to undergo the reverse reaction to re-form carbon disulfide. Carbon diselenide tends to polymerize easily, but it does react with oxygen, nitrogen, and carbon nucleophiles.
Isocyanates (R1NCO) are produced industrially by reaction of phosgene (COCl2) with primary amines (R1NH2). On a small scale, the Curtius rearrangement of acyl azides 5 is a more convenient method (Scheme 6).[15–17] Isothiocyanates (R1NCS) are less electrophilic than the corresponding isocyanates and many are relatively hydrolytically stable. Reaction with oxygen, sulfur, and nitrogen nucleophiles gives rise to thiocarbamates, dithiocarbamates, and thioureas respectively.[18]
Scheme 6 Isocyanates from Curtius Rearrangement of Acyl Azides[15–17]
The stability of carbodiimides (R1N=C=NR2) is dependent on the nature of the nitrogen substituents. Most are stable at room temperature but decompose or polymerize on heating. Carbodiimides are important reagents for the activation of carboxylic acids in peptide-coupling reactions, which are often catalyzed by a hypernucleophilic acylation catalyst such as 1H-benzotriazol-1-ol (1-hydroxybenzotriazole, BtOH) (Scheme 7).[19,20]
Scheme 7 Peptide Coupling by Carbodiimide and 1H-Benzotriazol-1-ol[19,20]
The heterocumulenes containing a C=P bond are less stable than the corresponding oxygen or nitrogen species. The oxaphosphapropadienes (R1P=C=O) and azaphosphapropadienes (R1P=C=NR2) undergo nucleophilic attack at the carbon atom. In contrast, the 1λ5,3λ5-diphosphapropadienes (carbodiphosphoranes) 6 are strongly basic on the carbon due to the importance of the ylidic resonance forms (Scheme 8). Diphosphapropadienes (R1P=C=PR2) are less highly polarized and undergo both electrophilic and nucleophilic attack at phosphorus.
Scheme 8 Resonance Forms of Carbodiphosphoranes
Section 18.3 covers carbonic acid halides. Due to the electronegativity of both the halogen and the other heteroatom, these compounds all display electrophilic character at the central carbon and the principal reaction involves nucleophilic attack by heteroatom nucleophiles such as alcohols, phenols, thiols, and amines (Scheme 9).
Scheme 9 Nucleophilic Substitution of Carbonic Acid Halides
Phosgene (COCl2) is commercially available and is the best-known member of this product class. Despite its high toxicity, it is widely used as a versatile, powerful electrophile for a wide range of nucleophiles. Reaction with alcohols is the most widely used method for the synthesis of chloroformates (R1OCOCl), which are commonly used for the protection of amines as carbamates 7 (Scheme 10).[21] Reaction of phosgene with thiols leads to chlorothioformate S-esters (R1SCOCl).[22]
Scheme 10 Carbamate Protection of Amines by Chloroformate Esters[21]
Reaction of phosgene with secondary amine hydrochlorides gives the corresponding carbamoyl chlorides 8 which can then react by further nucleophilic substitution with alcohols, thiols, and amines, to give carbamates, thiocarbamates, and ureas respectively (Scheme 11).[22]
Scheme 11 Stepwise Nucleophilic Substitution of Phosgene via a Carbamoyl Chloride[22]
The synthesis and applications of carbonic acids and esters are covered in Section 18.4. Monoesters of carbonic acid (R1OCO2H) are highly unstable with respect to decarboxylation to give alcohols and carbon dioxide. The corresponding metal salts (R1OCO2M), which are most simply prepared by the addition of a metal alkoxide to carbon dioxide, are much more stable. The most widely studied class of organocarbonates is the diesters (R1OCO2R2). These are classically produced by the reaction of phosgene and an alcohol in the presence of an organic base to give a chloroformate 9, which may be reacted with a second alcohol to form the carbonate diester 10 (Scheme 12).
Scheme 12 Organocarbonate Diesters from Alcohols and Phosgene
Bis(trichloromethyl) carbonate (11), which is known as triphosgene, is formed by photochemical chlorination of dimethyl carbonate. Triphosgene displays similar reactivity to phosgene itself but has the advantage of being a solid, thus making it significantly safer and easier to handle.[23] Reaction with nucleophiles leads to loss of trichloromethanol, which forms phosgene by loss of hydrogen chloride (Scheme 13).
Scheme 13 Synthesis of Triphosgene and Reaction with Nucleophiles To Liberate Phosgene[23]
Dialkyl dicarbonates [dialkyl pyrocarbonates, (R1OCO)2O] such as di-tert-butyl dicarbonate (12) are used as acylating agents, as alternatives to chloroformates. They are widely used in amino acid chemistry as protecting groups (Scheme 14).[24]
Scheme 14 Carbamate Protection of Amino Acids Using Di-tert-butyl Dicarbonate[24]
Seleno- and tellurocarbonates are photosensitive and are less stable than the corresponding carbonates. Selenocarbonic acid O,Se-diesters 13 can be prepared by reaction of a selenol with an alkyl chloroformate (Scheme 15).[25] Reduction of selenocarbonic acid diesters 13 by tributylstannane leads to the corresponding alkoxycarbonyl radical 14, which may cyclize onto an appropriately placed radical acceptor, such as an alkene, or decarboxylate to form an alkyl radical (Scheme 15).[25]
Scheme 15 Formation of Selenocarbonic Acid O,Se-Diesters and Homolysis To Form an Alkoxycarbonyl Radical[25]
Polycarbonates (Section 18.5) are most commonly synthesized by the reaction of a diol (or diphenol) with phosgene (Scheme 16). They are commercially extremely important due to their high stability and excellent physical properties such as toughness, electrical insulation, and flame resistance.
Scheme 16 Polycarbonates from the Polycondensation of a Diol and Phosgene
Section 18.6 outlines the synthesis and applications of carbamic acid derivatives. The parent compound, carbamic acid (H2NCO2H), is unstable with respect to decarboxylation and has not been isolated. Carbamate salts (R1R2NCO2− X+; X = NH4, metal) are readily formed and may be used for elaboration to carbamate esters (R1R2NCO2R3). The most common application of carbamate esters is as protecting groups for the amine function.[26] The basis for this protection is the conjugation between the nitrogen lone pair and the carbamate carbonyl group which renders the nitrogen less nucleophilic. Carbamate protection is most often accomplished by reaction of an amine with either a chloroformate ester (Scheme 10) or a dialkyl dicarbonate (Scheme 14).[21,24] In peptide-coupling reactions between amino acid derivatives, the use of carbamate protecting groups is found to lead to less racemization during base-catalyzed coupling of carboxy-activated acids.[20,26]
Carbamate esters are also prepared by nucleophilic attack of an alcohol on a suitable electrophile such as an isocyanate 15 (Scheme 17). This reaction is often catalyzed by either base (to activate the alcohol) or a Lewis acid (to activate the isocyanate).
Scheme 17 Synthesis of Carbamate Esters by Nucleophilic Addition of Alcohols to Isocyanates
Cyclic carbamate esters are synthesized by reaction of the corresponding amino alcohol with phosgene or a phosgene equivalent such as bis(trichloromethyl) carbonate (11), trichloromethyl chloroformate (diphosgene, 16),[27] 1,1′-carbonyldiimidazole (17),[28] or a dialkyl carbonate 18 (Scheme 18). Chiral oxazolidinones, especially N-acyl derivatives 19 (R5 = COR7), have found widespread use as chiral auxiliaries for asymmetric reactions such as aldol reactions,[29] enolate alkylation,[30] and Diels–Alder cycloadditions.[31] Achiral N-acyloxazolidinones 19 (R5 = COR7) have also been extensively employed as metal-chelating substrates in a variety of asymmetric metal-catalyzed transformations.[32–37]
Scheme 18 Synthesis of Oxazolidinones from Amino Alcohols by Reaction with Phosgene Equivalents[27,28]
Free thiocarbamic S-acid (H2NCOSH) is unstable but metal and ammonium thiocarbamates 20, which can be conveniently formed by addition of amines or metal amides to carbon monoxide in the presence of sulfur, are much more stable. Thiocarbamate salts are used as intermediates for the synthesis of ureas, thiocarbamate S-esters 21, carbamic acid esters, and isocyanates. Alkylation of thiocarbamate anions occurs preferentially on sulfur, the soft nucleophilic center (Scheme 19).[38]
Scheme 19 Synthesis of Thiocarbamate S-Esters[38]
Selenocarbamates (R1R2NCOSeR3) are used as precursors to carbamoyl radicals which may subsequently react with a suitable radical trap, e.g. by cyclization onto a pendant alkene to form a lactam. This is directly analogous to the reaction of selenocarbonates (Scheme 15).[39]
Section 18.7 is focused on polyurethanes, which are the only industrially important class of carbamic acid based polymer. The synthesis of polyurethanes is normally achieved by condensation of a diol with a diisocyanate (Scheme 20). The sulfur analogues, polythiocarbamates, which are synthesized by addition of thiols to isocyanates, are much less important due to the unpleasant odor of the thiol monomers and the lower thermal stability of the polymers.
Scheme 20 Synthesis of Polyurethanes by Polycondensation of Diols and Diisocyanates
The synthesis of ureas is covered in Section 18.8. The direct synthesis of ureas by reaction between an amine and carbon dioxide requires high temperatures and pressures, or the use of expensive or toxic dehydrating agents to remove the water which is formed as a byproduct. The simplest synthesis involves the condensation of an amine with phosgene, which can be used to form unsymmetrical ureas 23 (R1 ≠ R2) if the stoichiometry of the first addition is controlled in order to produce the isocyanate intermediate 22 (Scheme 21).[40,41] In fact, the wide availability of isocyanates by a range of methods makes them the most commonly used precursors for large scale urea synthesis.
Scheme 21 Synthesis of Ureas by Reaction of Amines with Phosgene[40,41]
Dihydropyrimidines 24 are cyclic ureas which display a range of important pharmacological properties. They can be synthesized by the Biginelli reaction, an acid-catalyzed, one-pot, three-component coupling between an aldehyde, a β-dicarbonyl compound, and a urea (Scheme 22).[42,43] Cyclic ureas 25 have also been produced by a variation of the Ugi reaction, involving a five-component coupling (Scheme 22).[44]
Scheme 22 Synthesis of Dihydropyrimidines by Biginelli, Three-Component Coupling, and Ugi, Five-Component Coupling Reactions[42–44]
Polymeric ureas are covered in Section 18.9 and are most commonly formed by nucleophile-initiated polymerization of isocyanates 26 or by the copolymerization of diisocyanates 27 and diamines (Scheme 23). Polyureas find widespread use as elastomers, foams, fibers, and spray coatings. Condensation of urea with formaldehyde produces urea–formaldehyde resins which are industrially very important, and are used in particular for the manufacture of adhesives.
Scheme 23 Synthesis of Polyureas
Thiocarbonic acid derivatives are the focus of Section 18.10. The principle differences between the thiocarbonyl species and the corresponding carbonyl compounds result from the weaker C=S vs C=O bond, the softer nature of the sulfur as a nucleophile, and the greater ease of oxidation of the sulfur. Thiophosgene (CSCl2) reacts readily with a range of heteroatom nucleophiles to form other thiocarbonic acid derivatives. These reactions may be controlled in a stepwise manner to give access to the chlorocarbonothioyl species 28, thus allowing the synthesis of unsymmetrical thiocarbonic acid derivatives 29 (Scheme 24).[45]
Scheme 24 Synthesis of Thiocarbonic Acid Derivatives by Stepwise Nucleophilic Substitution of Thiophosgene[45]
Conversion of 1,2-diols into 1,3-dioxolane-2-thiones 30 is the basis for the Corey–Winter alkenation reaction. Heating the thiones 30 in the presence of a thiophile such as trimethyl phosphite leads to stereospecific reductive decarboxylation to give the corresponding alkene 31 (Scheme 25).[46]
Scheme 25 Corey–Winter Alkenation Reaction[46]
Dithiocarbonate O,S-diesters 33 are commonly termed xanthates. They are often prepared by reaction of an alkoxide with carbon disulfide and trapping of the resulting xanthate anion 32 with an alkyl halide (Scheme 26). Thiocarbonate O,O-diesters 34 (X = O) and dithiocarbonate O,S-diesters 34 (X = S) may both be used in the Barton–McCombie deoxygenation of alcohols under radical reducing conditions (Scheme 26).[47,48]
Scheme 26 Synthesis of Dithiocarbonate O,S-Diesters (Xanthates) and the Barton–McCombie Deoxygenation Reaction[47,48]
Seleno- and tellurocarbonic acid derivatives are covered in Section 18.11. Although some selenocarbonic acid derivatives are stable, many are thermally and photolytically unstable. The increased bond length and poorer π-overlap makes the corresponding tellurocarbonic acid derivatives less stable still. Selenocarbonyl difluoride is known, but the dichloride (selenophosgene) has only been reported once. In contrast, selenocarbonates [R1OC(Se)XR2; X = O, S, Se] have been more widely studied. Cyclic selenocarbonates, selenocarbamates, and selenoureas can all be made by reaction of carbon diselenide with a difunctional nucleophile such as a diol, amino alcohol, or diamine but this approach is restricted by the limited availability of carbon diselenide and its tendency to polymerize. Cyclic 1,3-dioxolane-2-selones can be converted by reductive decarboxylation into the corresponding alkenes in a similar reaction to that of the thiones shown in Scheme 25.[49]
The Woollins reagent (35), which is analogous to the well-known thionating agent, Lawesson's reagent, has been developed for the conversion of carbonyl compounds into the corresponding selenocarbonyl species.[50] As shown in Scheme 27, N,N′-diethylurea reacts with the Woollins reagent to give the selenourea 36.[51]
Scheme 27 Oxygen–Selenium Exchange of N,N′-Diethylurea Using the Woollins Reagent[51]
Section 18.12 deals with imidic acids, based on the XC(=NR1)Y unit, and the corresponding C=P species. Carbonimidic dihalides [XC(=NR1)Y; X = Y = halo] and the related iminium salts [XC(=N+R1R2)Y; X = Y = halo] are highly electrophilic and one or both halides may be displaced by heteroatom nucleophiles to give either other imide derivatives 37 or heterocumulenes 38, such as carbodiimides, isocyanates, and isothiocyanates (Scheme 28).[52,53]
Scheme 28 Nucleophilic Substitution of Carbonimidic Dihalides[52,53]
The corresponding phosphaalkenes (X2C=PR1) are often unstable, depending on the nature of the substituent on phosphorus. Stable species commonly bear a very large phosphorus substituent which provides steric protection.
Guanidines are covered in Section 18.13. They are among the strongest organic bases (pKaH ∼12) due to the powerful resonance stabilization of the protonated form (Scheme 29). The synthesis of guanidines is often hampered by their strong basicity and polarity, which can be sufficient to make them water soluble, especially if the nitrogens are not alkylated or protected with an electron-withdrawing group. Substituted guanidines can be prepared by the addition of substituents to a pre-existing guanidine core, e.g. by alkylation or condensation with carbonyl compounds, but the most common methods for guanidine synthesis involve reaction of an amine with an amidine derivative bearing a leaving group. Typical amidine equivalents include cyanogen bromide (BrCN), carbodiimides (R1N=C=NR2), and thioureas [R1NHC(S)NHR2].[54]
Scheme 29 Resonance Stabilization of Guanidinium Cation
Section 18.14 deals with analogues of guanidine in which one or more of the nitrogen atoms is replaced by a phosphorus. The most widely used method for the formation of phosphaguanidines 39 is by addition of a phosphine nucleophile to a carbodiimide (Scheme 30).[55] Addition of phosphorus(III) nucleophiles to carbonimidic dichlorides (Cl2C=NR1) is used to prepare imines with two phosphorus substituents, and the use of phosphite esters leads to the phosphorus(V) species 40 by an Arbuzov-type reaction.[56] There are no general methods for the synthesis of phosphorus analogues of guanidines which contain the phosphaalkene (C=P) group, although many such compounds have been prepared.
Scheme 30 Synthesis of Phosphaguanidines[55,56]
Compounds with four single bonds to heteroatoms are discussed in Sections 18.15 and 18.16. Section 18.15 covers those compounds in which at least one of the heteroatoms is a halogen. Tetrahalomethanes include simple one-carbon chlorofluorocarbons (CFCs), which have been used as refrigerants and aerosol propellants, and compounds such as carbon tetrachloride, which has been used as a relatively stable nonflammable solvent. The use of highly halogenated alkanes has been drastically reduced in view of their potential for damage to the environment through ozone depletion. Many tetrahalomethanes can be prepared by decarboxylative halogenation of trihaloacetates 41 (Scheme 31).
Scheme 31 Synthesis of Tetrahalomethanes by Decarboxylative Halogenation of Trihaloacetates
Trifluoromethyl hypofluorite (F3COF) has been used as an electrophilic fluorinating agent for reaction with aromatic rings and silyl enol ethers derived from a variety of carbonyl compounds.[57] Perhaps the best-known series of trifluoromethyl compounds is that based on the sulfonic acid and its derivatives. Trifluoromethanesulfonic acid (triflic acid) is very powerfully acidic and hence, the trifluoromethanesulfonate (triflate) anion (CF3SO3−) is an excellent leaving group. In fact, solvolysis of alkyl trifluoromethanesulfonates is 105–107 times faster than that of alkyl halides or 4-toluenesulfonates.[58] Trifluoromethanesulfonic anhydride is a powerful hard electrophile and reacts with a wide range of heteroatom nucleophiles to give the corresponding trifluoromethanesulfonates. Conversion of alcohols into trifluoromethanesulfonate esters allows displacement of the hydroxy group by nucleophiles.[59] Vinyl and aryl trifluoromethanesulfonates 43, prepared by reaction of trifluoromethanesulfonic anhydride with enolates or phenols respectively, have found widespread use in transition metal mediated coupling reactions due to the ease of oxidative addition into the C—O bond of the trifluoromethansulfonate (Scheme 32). N-Phenylbis(trifluoromethanesulfonamide) (42), McMurry's reagent, is also an excellent trifluoromethanesulfonyl donor and has the advantages of being much more stable than trifluoromethanesulfonic anhydride, being less reactive and therefore more selective, and being a crystalline solid and hence easier to handle.[60,61]
Scheme 32 Synthesis of Vinyl and Aryl Trifluoromethanesulfonates and Oxidative Addition to Coordinatively Unsaturated Transition-Metal Complexes
Section 18.16 covers compounds with four single bonds to heteroatoms, none of which are halogen. Most of the many possible permutations involving oxygen, nitrogen, sulfur, and phosphorus have in fact been reported. Orthocarbonic acid tetraesters [C(OR1)4] have found use in the synthesis of polymers for biodegradable plastics, resins, and dental restoratives. Their reaction with Lewis acids, such as boron trifluoride–diethyl ether complex, leads to the formation of trialkoxycarbenium salts 44. The triethyl derivative 45, Meerwein's reagent, is commercially available and is used as powerful, hard electrophilic alkylating agent (Scheme 33).[62,63]
Scheme 33 Synthesis of Trialkoxycarbenium Salts and Reaction of Meerwein's Reagent with Diethyl Ether[62,63]
Orthocarbonates have been used as protecting groups for alcohols, amines, and carbonyl groups.[26] As expected for an acetal-like species, they are stable under basic conditions, but may be hydrolyzed in acid. Thermal decomposition of dihydrooxadiazoles 46 has been used in the study of dialkoxycarbenes 47 (Scheme 34).[64] Carbenes 47 are also produced by thermolysis of dialkoxydiazirines 48.[65]
Scheme 34 Formation of Dialkoxycarbenes by Thermolysis of Dihydrooxadiazoles and Dialkoxydiazirines[64,65]
Orthocarbonic acid diester diamides [urea acetals, (R1O)2C(NR2R3)2] undergo a variety of reactions, often involving nucleophilic displacement of either an alkoxy or an amino group depending on the nature of the nucleophile.[66] Tetrathioorthocarbonates [C(SR1)4] are stable and have been used as monomers for polymer synthesis. In contrast, the corresponding tetrakis(dialkylamino)methanes [C(NR1R2)4] may be isolated but are thermally unstable and hydrolyze readily to form hexaalkylguanidinium salts.[67]
References
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