The formation of carbon-heteroatom bonds

The Ullmann-Goldberg reaction constitutes an excellent method for the crosscoupling of aryl halides with a variety of electrophiles.203 

Anilines and 2-chlorobenzoic acids, used in the synthesis of non-steroidal antiinflammatory agents, react in 20 min, instead of several hours without sonication (Fig. 36).204 Precursors of acridinones and aromatic ethers were prepared with a similar methodology.205/206 reactions proceed in a much cleaner manner and afford products of higher purity than the conventional methods. No specific studies of the sonochemical activation were done in these cases. 

These reactions include bond formation between carbon and the heteroatom such as silicon, tin, or germanium, and homocoupling of these heteroelemental 

As a model for cross-coupling reactions, sonication of 3-bromothiophene, trimethylchlorosilane, and magnesium generates 3-trimethylsilylthiophene in good yields.209 Xhe reaction requires THF as the solvent (Eq. 47). 

Hindered chlorosilanes (f-butyldimethyl, phenyldimethyl, tri-f-propyl) do not react. Moderate success (yields ca. 30-40%) was obtained in the synthesis of amino-silanes (Eq. 48), but this reaction accommodates hindered silyl (e.g., triphenyl) 

---

When reductive elimination from a late transition metal involves the formation of a carbon-carbon bond, the process is intramolecular and the groups have to be aligned cis to one another in the complex. In the formation of carbon-heteroatom bonds the reductive elimination from palladium might take place via competing pathways.16... 

The formation of carbon-heteroatom bonds can be effected by reactions of hypervalent iodine reagents with a wide range of organic substrates and inorganic nucleophiles, and represents one of the most popular applications of organoiodine(III) compounds [1-10]. Except for C-I(III) bond forming reactions used for the synthesis of iodanes and iodonium salts, C-heteroatom bond formation is almost always accompanied by reduction of the hypervalent iodine reagents to iodine(I) compounds. 

Asymmetric synthesis of heterocycles from olefins via cyclization with the formation of carbon-heteroatom bonds 84MI1. 

Reactions involving the formation of carbon heteroatom bonds include the industrially best known photochemical reactions. In fact, chlorination, bromination and sulfochlorination are major processes in industrial chemistry, and oxygenation has likewise an important role. Due to the focus on fine chemistry of this chapter, the discussion below is limited to laboratory-scale preparations and in particular to some bromination and oxygenation reactions illustrating the advantage of the photochemical approach, as well as to some alkoxylation, hydroxylation and amination reactions. 

In his Nobel lecture, Suzuki has summarized work on the use of organoboranes in the formation of carbon-carbon bonds.A wide-ranging review has been published covering the transmetalation reactions involving the use of organoboron compounds in the formation of metal-carbon bonds.There has also been a review of the use of copper-promoted reactions of arylboronic acids in the formation of carbon-heteroatom bonds. 

The photocatalytic generation of aryl radicals was also successfully applied to the formation of carbon heteroatom bonds. The aryl pinacolboronates 141 can be easily achieved by visible light irradiation of a solution of aryl diazonium salts 142 and diboron pinacol ester 143 containing 5mol% of eosin (Scheme 29.24) [89]. The proposed meehanism involves the addition of aryl radical 144 to the complex 145 that is generated by interaction of tetrafluoroborate anion and diboran pinacol ester 143. This process leads to the formation of the aryl pinacolboronates 141 and the radical anion intermediate 146. The oxidation of this intermediate by eosin radical cation completes the catalytic cycle. 

The formation of carbon—heteroatom bonds is generally more straightforward than the formation of carbon-carbon bonds because of the difference in electronegativity between carbon and heteroatom. This concept carries over to electrocyclic processes as well, but with a caveat Because of the difference in electronegativity, polar mechanisms may compete with the electrocycUzation. The mechanistic complexity of these systems notwithstanding, there are obvious applications of such reactions for the synthesis of heterocycles. Muller and List s results are shown in... 

Our review of the use of organoboron compounds in radical chemistry will concentrate on applications where the organoborane is used as an initiator, as a direct source of carbon-centered radicals, as a chain transfer reagent and finally as a radical reducing agent. The simple formation of carbon-heteroatom bonds via a radical process is not treated in this review since it has been treated in previous review articles [3,9]. 

Examples of the transition metal catalyzed formation of carbon-heteroatom bonds other than carbon-nitrogen are less abundant. In a recent survey of the copper catalyzed carbon-oxygen bond formation between alcohols and organotrifluroborates the coupling of 3-thienyltrifluoroborate and 2-furfuryl alcohol gave the expected thienyl-furfuryl-ether in good yield (6.83.),113... 

Substitutions such as alkylation (Chapter 5) and oxygenation (Chapter 9) are fundamental transformations essential to the chemistry of hydrocarbons. Other heterosubstitutions (i.e., formation of carbon-heteroatom bonds), such as halogenation, nitration, or sulfuration (sulfonation), are also widely used reactions. It is outside the aim of our book to discuss comprehensively the wide variety of substitution reactions (for a scope, see, e.g., March s Advanced Organic Chemistry), but it is considered useful to briefly review some of the most typical selected heterosubstitutions of hydrocarbons. 

The Volume Editors have spent great time and effort in considering the format of the work. The intention is to focus on transformations in the way that synthetic chemists think about their problems. In terms of organic molecules, the work divides into the formation of carbon-caifoon bonds, the introduction of heteroatoms, and heteroatom interconversions. Thus, Volumes 1-S focus mainly on carbon-carbon bond formation, but also include many aspects of the introduction of heteroatoms. Volumes 6-8 focus on interconversion of heteroatoms, but also deal with exchange of carbon-caibon bonds for carbon-heteroatom bonds. 

This compilation embraces a wide variety of subjects, such as solid-phase and microwave stereoselective synthesis asymmetric phase-transfer asymmetric catalysis and application of chiral auxiliaries and microreactor technology stereoselective reduction and oxidation methods stereoselective additions cyclizations metatheses and different types of rearrangements asymmetric transition-metal-catalyzed, organocatalyzed, and biocatalytic reactions methods for the formation of carbon-heteroatom and heteroatom-heteroatom bonds like asymmetric hydroamina-tion and reductive amination, carboamination and alkylative cyclization, cycloadditions with carbon-heteroatom bond formation, and stereoselective halogenations and methods for the formation of carbon-sulfur and carbon-phosphorus bonds, asymmetric sulfoxidation, and so on. 

Figure 10.3-40. The rating for the disconnection strategy carbon-heteroatom bonds is illustrated, Please focus on the nitrogen atom of the tertiary amino group. It is surrounded by three strategic bonds with different values. The low value of 9 for one ofthese bonds arises because this bond leads to a chiral center. Since its formation requires a stereospecific reaction the strategic weight of this bond has been devalued. In contrast to that, the value of the bond connecting the exocyclic rest has been increased to 85, which may be compared with its basic value as an amine bond.

From the recent advances the heteroatom-carbon bond formation should be mentioned. As for the other reactions in Chapter 13 the amount of literature produced in less than a decade is overwhelming. Widespread attention has been paid to the formation of carbon-to-nitrogen bonds, carbon-to-oxygen bonds, and carbon-to-sulfur bonds [29], The thermodynamic driving force is smaller in this instance, but excellent conversions have been achieved. Classically, the introduction of amines in aromatics involves nitration, reduction, and alkylation. Nitration can be dangerous and is not environmentally friendly. Phenols are produced via sulfonation and reaction of the sulfonates with alkali hydroxide, or via oxidation of cumene, with acetone as the byproduct. 

The most important organic reactions -in vitro as well as in vivo-, leading to the formation of carbon-carbon (or carbon-heteroatom) bonds are, generally speaking, of ionic or polar nature (see, however. Heading 5.5). 

An example of C—Si bond formation concludes this overview of carbon heteroatom bond formation. Reflux of bromide 62 in benzene and in the presence of small amounts of (TMS)3SiH and AIBN afforded the silabicycle 63 in 88 % yield (Reaction 7.64) [76]. The key step for this transformation is the intramolecular homolytic substitution at the central silicon atom, which occurred with a rate constant of 2.4 x 10 s at 80 °C (see also Section 6.4). The reaction has also been extended to the analogous vinyl bromide (Reaction 7.65) [49]. 

A. 1.1. Covalently Functionalized Dendrimers Applied in a CFMR The palladium-catalyzed allylic substitution reaction has been investigated extensively in the preceding decades and provides an important tool for the formation of carbon—carbon and carbon—heteroatom bonds 14). The product is formed after attack of a nucleophile to an (f/ -allyl)Pd(II) species, formed by oxidative addition of the unsaturated substrate to palladium(0) (Scheme 1). To date several nucleophiles have been used, mostly resulting in the formation of carbon—carbon and... 

After the discovery of the first terminal vinylidene-metal complex in 1972, it was established that the stoichiometric activation of terminal alkynes by a variety of suitable metal complexes led to 1,2-hydrogen transfer and the formation of metal-vinylidene species, which is now a classical organometallic reaction. A metal-vinylidene intermediate was proposed for the first time in 1986 to explain a catalytic anti-Markovnikov addition to terminal alkynes. Since then, possible metal-vinylidene intermediate formation has been researched to achieve catalytic regiose-lective formation of carbon-heteroatom and carbon-carbon bonds involving the alkyne terminal carbon. 

The exchange of a halogen to a classical nitrogen or oxygen nucleophile usually proceeds readily on the purine skeleton, without the necessity of using a transition metal catalyst. There are certain cases, however, where the palladium catalyzed carbon-heteroatom bond formation might take preference over noncatalysed methods. Inosine derivatives, for example,... 

The biaryl synthesis by Ullmann coupling, as well as a large number of related coupling reactions, constitutes another type of copper-mediated or -catalyzed reaction used extensively for the formation of carbon-carbon and carbon-heteroatom bonds. These transformations have been reviewed recently17,177,177a,177b and will not be discussed in detail here. 

---