Introducing Functionality

As we have seen in the previous section, it may be easy to construct the carbon skeleton of the target compound of a synthesis, but with a reactive functional group at the wrong carbon. Therefore it is important also to have practice at shifting reactive entry points around to achieve the final desired product. We shall illustrate this form of molecular chess with reactions from previous chapters. A typical problem may be to devise syntheses for achieving the following conversions  

Production of 4-methyl- 1-pentanol from the substituted alkylborane, 7, can be achieved by oxidation (Section 11-6D)  

The three steps —hydroboration, isomerization, and oxidation—thus constitute a reasonable synthesis of the first desired compound. 

The second desired product is a little more tricky because the isomerization of 6 to 7 cannot be stopped at the alkylborane, 8  

The best procedure to get the desired product is to generate the 1-alkene from the borane with 1-decene (Section 11-6C) and then add hydrogen bromide by a polar mechanism (Section 10-4). Incursion of radical-chain addition must 

---

In several important cases, new synthetic strategies have been developed into new production schemes. An outstanding example of this is the production of an entire family of terpene derivatives from a-pinene (29), the major component of most turpentines, via linalool (3) (12). Many of these materials had been produced from P-pinene, a lesser component of turpentine, via pyrolysis to myrcene and further chemical processing. The newer method offers greater manufacturing dexibiUty and better economics, and is environmentally friendly in that catalytic air oxidation is used to introduce functionality. 

Bicomponent technology has been used to introduce functional and novelty effects other than stretch to nylon fibers. For instance, antistatic yams are made by spinning a conductive carbon-black polymer dispersion as a core with a sheath of nylon (188) and as a side-by-side configuration (189). At 0.1—1.0% implants, these conductive filaments give durable static resistance to nylon carpets without interfering with dye coloration. Conductive materials such as carbon black or metals as a sheath around a core of nylon interfere with color, especially light shades. 

The first step in reducing the computational problem is to consider only the valence electrons explicitly, the core electrons are accounted for by reducing the nuclear charge or introducing functions to model the combined repulsion due to the nuclei and core electrons. Furthermore, only a minimum basis set (the minimum number of functions necessary for accommodating the electrons in the neutral atom) is used for the valence electrons. Hydrogen thus has one basis function, and all atoms in the second and third rows of the periodic table have four basis functions (one s- and one set of p-orbitals, pj, , Pj, and Pj). The large majority of semi-empirical methods to date use only s- and p-functions, and the basis functions are taken to be Slater type orbitals (see Chapter 5), i.e. exponential functions. 

Reactions of the type shown in (ii) and (34) are called substitution reactions. The substitution reaction is the characteristic reaction of benzene and its derivatives and is the way in which a multitude of compounds are prepared by the organic chemist. By this means he is able to introduce functional groups, which can then be... 

Although retrosynthetic simplification of intermediate 9 introduces functionality and would appear to complicate matters, retro-... 

A common feature of the reactions in this section is that they serve to introduce functionality at a position remote from functional groups already present. As such, they have proved very useful in synthesizing many compounds, especially in the steroid field (see also 19-2 and 19-14). When N-haloamines in which one alkyl group has a hydrogen in the 4 or 5 position are heated with sulfuric acid, pyrrolidines or piperidines are formed, in a reaction known as the Hofmann-Loffier reaction... 

Examples of Dienes and Dienophiles. The synthetic value of D-A reactions can be enhanced in various ways. In addition to hydrocarbon dienes, substituted dienes can be used to introduce functional groups into the products. One example that illustrates the versatility of such reagents is l-methoxy-3-trimethylsiloxy-l,3-butadiene... 

Aromatic nitro compounds undergo nucleophilic aromatic substitutions with various nucleophiles. In 1991 Terrier s book covered (1) SNAr reactions, mechanistic aspects (2) structure and reactivity of anionic o-complexes (3) synthetic aspects of intermolecular SNAr substitutions (4) intramolecular SNAr reactions (5) vicarious nucleophilic substitutions of hydrogen (VNS) (6) nucleophilic aromatic photo-substitutions and (7) radical nucleophilic aromatic substitutions. This chapter describes the recent development in synthetic application of SNAr and especially VNS. The environmentally friendly chemical processes are highly required in modem chemical industry. VNS reaction is an ideal process to introduce functional groups into aromatic rings because hydrogen can be substituted by nucleophiles without the need of metal catalysts. 

Such manipulation mostly depends on the characteristics of the ring structures and their functional groups. It might be necessary to introduce functional groups selectively into small ring systems, but the direct functionalization of ring carbon atoms is rather difficult. Thus the availability of functionalized ring compounds is an important factor. 

Lautens also used this nickel-catalyzed hydroalumination methodology in the total synthesis of ionomycin 145. The starting compound was a [3.2.1]oxabicyclic alkene 143.144 Their rigid bicyclic structures can be used to introduce functional groups in a highly stereoselective manner. The synthesis of the key intermediate 144 involves the slow addition of DIBAL to the oxabicyclic alkene and the Ni(COD)2/(6T)-BINAP in toluene to afford 144 in 95% yield and 93-95% ee. (Scheme 18). 

Most immobilization methods require modification of the ligands for anchoring to the support by introducing functional groups such as vinyl, trialkoxysilyl, sulfonic acid, and amino groups. The consequence is often a more elaborate synthesis of the ligand, which adds to the costs of an immobilized catalyst. However, two interesting approaches were developed in recent years, when unmodi-... 

Methods for introducing functional groups into Co(C2B3)M triple-deckers, important in many synthetic strategies for constructing multicage oligomers and polymers (Section 3.01.4.5), have been developed with the synthesis of... 

Several catalytic processes are known, see below, but it is clear that the compatibility of the above chemistry with functionalisation is limited. Many reagents used to introduce functional groups will react with the reactive intermediates described above, and the alkanes will have no opportunity to react with the catalyst. Below a few catalytic reactions will be described of relatively electron-rich metal complexes. 

It was discussed earlier how a major hurdle for the manipulation of CNTs is their insolubility in most organic and aqueous solvents, and how introducing functional groups is a simple and powerful tool to improve solubility. However, the first functionalization step is expected to be the most problematic due to the primary utilization of as yet nonfunctionalized pristine nanotubes. 

Even today, most researchers choose to oxidize nanocarbons (i.e. acid treatment) prior to hybridization in order to introduce functional groups and so render them hy-... 

Since it was shown that free radical ring-opening polymerization (2) made it possible to introduce functional groups, such as esters C3j, carbonates (4), thioesters (5), and amides (6), into the backbone of an addition polymer, it was reasoned that simple hydrolysis would produce the desired oligomers that could be terminated with various combinations of hydroxyl, amino, thiol, and carboxylic acid groups. 

---