Synthetic exploitation

In the third example of the previous paragraph [9], the reaction conditions described are similar to those used for the enzymatic transformations in bulk organic media, an area that was pioneered by Klibanov and coworkers in the 1980s [12] and later investigated and synthetically exploited worldwide [13]. 

Scheme 9.27 Synthetic exploitation of enantiocomplementary biocatalytic sulfoxidations.

With the ArH ArTlX2 Arl reaction sequence available as a rapid and reliable probe for aromatic thallation, a detailed study was undertaken of the various factors affecting orientation in this electrophilic metallation process (153). The results, which are summarized below, demonstrate that aromatic thallation is subject to an almost unprecedented degree of orientation control coupled with the ease with which thallium can then be displaced by other substitutent groups (this aspect of the synthetic exploitation of aromatic thallation is discussed in detail below), the sequential processes of thallation followed by displacement represent a new and versatile method for aromatic substitution which both rivals and complements the classic Sandmeyer reaction. 

A simplified mechanism for the Beckmann rearrangements and important related reactions is shown hi Scheme 9. Summarizing the mechanism section, the key step of the reaction is the migration of an a-carbon group to the electronically deficient nitrogen atom of the oxime. A nitrilium ion in some cases or an imidate in others are key intermediates in the reaction. Their destiny determines the course of the transformation. Basically, three different pathways may be possible and can be synthetically exploited ... 

The second chapter addresses new facets of the medicinal chemistry of the important anticancer drug Taxol (paclitaxel). Ojima and coworkers explore, in particular, the structure-activity relationship associated with the 3-phenylisoserine side chain, synthetically exploiting their P-Lactam Synthon Method . Their research has led to, among other things, a series of noteworthy second-generation taxoid anticancer agents. 

The photochemistry of ethers and related compounds (e.g. epoxides, acetals and hemi-acetals) is still relatively an unexplored field. Although activity in this field has increased recently, further work remains to be done and synthetic exploitation is still open to investigation. 

There are several reasons for the interest in controlled photocycloadditions. First, a cycloaddition (the 2+2, for example) allows access to the four-member ring system. Second, investigation of the regio- and stereochemical outcome of the cyclization process allows for a better understanding of the mechanistic pathway the reaction takes. The reaction is studied not only for synthetic exploitation, but for basic understanding of the photochemical process. 

Asymmetric Pummerer rearrangement is a very attractive reaction as previously described. In particular, the reactions induced by SKA work well, and may be synthetically exploited in many cases. The results described here demonstrate that the stereoselective a-deprotonation of the sulfoxide is a prerequisite process for asymmetric induction in the Pummerer reaction. Since many kinds of synthetic and enzymatic preparative methods of optically pure sulfoxides have been developed, the present Pummerer-type reaction will be applicable to many other chiral sulfoxides with one a-substituent, chiral vinylsulfoxides and chiral co-carbamoylsulfox-ides, thus leading to enantioselective syntheses of many new bioactive compounds in the near future. 

Carbometallations, i.e. reactions in which a new metallo-organic species 3 is formed by (formal) 1,2-addition of a metallo-organic species 1 along a multiple C-C bond 2, exhibit a great synthetic potential [1]. After all, not only is a new C-C bond formed during the course of the reaction, but also a carbon-metal bond that is directly available for further synthetic exploitation. 

The most curious point respecting volume of activation considerations, however, relates to synthetic applications. While high pressure is now often employed to secure intermolecular Diels-Alder adducts that could not otherwise be formed in reasonable yields, there has been little iq>plication of the same tactic to recalcitrant [2 + 2] cycloadditions. The opportunities for synthetic exploitations of the mechanistically oriented A0 determinations for [2 + 2] cycloadditions seem essentially untapped (and enormous). 

Indeed, it was the use of partial esterification that enabled the great synthetic exploitation of levoglucosan (6), the most readily accessible 1,6-anhydrohexopyranose. The steric interaction of the axial 3-hy-droxyl group with the 1,6-anhydro bridge is accentuated on reaction with the bulkier acid chlorides or anhydrides in pyridine in such a way that this hydroxyl group is esterified substantially more slowly than the other axially oriented ones. Consequently, the dimolar esterification of 6 with p-toluenesulfonic anhydride,156 benzyloxycarbonyl chloride,520 p-toluenesulfonyl chloride,38 106,156 505 520 636 benzoyl chlo-... 

Desilylation. The powerful desilylation ability of BU4NF makes it useful for generating various carbanion equivalents. Synthetic exploitations of this reactivity include access to homoallylamines from imines and an allylsilane, to p-hydroxy-a-diazoalkanoic esters from a-silyl-a-diazoacetic esters and aldehydes, and a-fluorovinylation of carbonyl compounds by 1-fluoro-l-methyldiphenylsilylsilylethylene. Benzyne is formed by treatment of phenyl 2-trimethylsilylphenyliodonium triflate" with BU4NF. 

Vigorous conditions are required and synthetic exploitation has been slight (147,212). Recent detailed studies by Bum and Cadogan (70, 72,73) have shown that substituents on phosphorus enhance the rate in the order RjN > R > RO > RS, and the rate was also increased by the use of solvents of increasing dielectric constant. They suggest that the alkylation of sulfur and dealkylation of oxygen may occur essentially simultaneously. 

As mentioned above, nitro compounds are obviously of great importance in organic chemistry and aryl nitro compounds are an important source of aniline derivatives (secs. 4.2.C.V, 4.8.D). Both amine oxides and nitrones have been synthetically exploited. Alkyl nitroso derivatives, however, usually cannot be isolated since they decompose in solution, although the aromatic derivatives are more stable in solution and can be used in synthesis (sec. 2.1 l.E). Treatment of a primary amine with excess peroxyacid is a useful preparative route to alkyl nitro compounds.588 Yields are highest for tertiary alkyl primary amines next come secondary, followed by primary alkyl. Peroxyacid oxidation of oximes also provides a route to alkyl nitro compounds.589 This method is convenient for preparing aromatic nitro compounds as in the oxidation of 2,6-dichloroaniline to 2,6-dichloronitrobenzene (441).590 Nitrones are 1,3-dipoles and have been used in 1,3-dipolar cycloaddition reactions (sec. ll.ll.D). 

Dihydrooxazoles are widely used as building blocks and auxiliaries in organic synthesis because of their accessibility and the mild hydrolytic conditions for ring-opening. The CH-acidity of 2-alkyl-4,5-dihydrooxazoles, the electrophilic reactivity at C-2 in A -alkyl-4,5-dihydrooxazolium salts and the activation of 2-aryl substituents in the 4,5-dihydrooxazole system in metalation reactions have all been synthetically exploited as shown in the following examples ... 

It was against this background diat Dow AgroSciences initiated an effort around the synthetic exploitation of the Antimycin A scaffold, aimed at addressing an optimum balance between desirable attributes and fungicidal potency and spectrum for this chemistry and MOA. 

The observation that sonochemistry and luminescent activities are not necessarily coincident had never been reported and suggests that the conditions at the root of sonoluminescence and sonochemistry could be different in nature (or in intensity). Chemical species as tracers should serve to describe the liquid flows the knowledge of which is of prime importance in medical ultrasound (microstreaming, acoustic streaming and/or rectified acoustic streaming zy Even if synthetic exploitations are difficult to imagine, some fundamental aspects of sonochemistry and cavitation still to be explored are very probably involved, and in this respect deserve further development. 

These results tend to demonstrate that an important S5mergetic effect can exist between ultrasound and light. At the present time, synthetic exploitations are practically absent. ... 

Synthetic exploitation of the aqueous aza Diels-Alder reaction... 

In addition to utilizing the heterocycloreversion of 2-azanorbomenes as an aqueous deprotection protocol for primary amines, where the formation of the transient iminium ion is incidental, 2-azanorbomene derivatives can also serve as precursors to iminium ions with the intention of synthetically exploiting these unstable intermediates. Such heterocycloreversion applications do not involve the use of aqueous media to avoid undesired hydrolysis of the newly generated iminium ion. The next few examples illustrate the use of 2-azanorbomenes as iminium-ion synthons unmasked by the reverse Diels-Alder process (see section 2.4.1). 

The development of efficient and practical aqueous 0x0 Diels-Alder methodology allowing for convenient access to substituted dihydropyrans and a-hydroxy-y-lactones set the stage for further synthetic exploitation. The following is a brief account of synthetic applications of the aqueous 0x0 Diels-Alder reaction. 

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