Nucleophilic transformation

Suitable chemistry must be chosen to allow the use of polyfunctional, unprotected reagents. In general, acylations and other reactions with electrophiles of a support-bound substrate will require the protection of functionalized side chains, both in the substrate and in the reagent. Protected, polyfunctional reagents are, however, rare and expensive, and protections/deprotections add further synthetic steps to the synthesis. Nucleophilic transformations, on the other hand, often enable the direct use of highly functionalized, unprotected reagents. Hence, nucleophilic transformations (e.g. 

Because of the stability of iron tricarbonyl diene complexes, conjugated dienals are protected from polymerization when complexed, while other reactions can be carried out at the aldehyde functionaUty. A number of synthetically attractive nucleophilic transformations of the aldehyde can be performed on these complexes. These include, aldol reactions, Michael additions, reactions with organozinc, -silicon, -boron, and -tin... 

Exo- and endo-cyclic ring closure reactions using 0-nucleophiles transform oxocarbenium ions into cyclic acetals. As an example of an endocyclic cyclization, epoxide ring opening of (96) with lithium dimethyl cuprate, and subsequent treatment of the resulting alcohol with acid, smoothly gives the bicyclic acetal (97), ° a key intermediate in the total synthesis of tirandamycic acid (Scheme 47). ... 

Similarly, cyclic sulfite and cyclic sulfate esters of the corresponding 1,2-diamines have been named 1,2,5-thiadiazole 1-oxide (5) and 1,2,5-thiadia-zole 1,1-dioxide (6). In this chapter, emphasis is placed on cyclic sulfites and cyclic sulfates however, the synthetic preparation and nucleophilic transformations of cyclic sulfamidites and cyclic sulfamidates are also compared. 

This feature of the reactions of azine W-oxides is of a general character. Indeed, the so-called deoxygenative nucleophilic transformations of azine W-oxides and their cationic forms into products have been established to involve the aMfo-aromatization step, in which the W-oxide, W-alkoxy, or W-acyloxy functions are auxiliary groups, facilitating elimination of hydrogen from the intermediate o -adducts (Scheme 19) [11, 45, 90-93] (for more details [215]). 

Nucleophilic transformation at the carbonyl group of DPP without cleavage of the bicycUc ring system corresponding to a formal replacement of O by S, N and C have also been investigated l... 

In stereoselective antitheses of chiral open-chain molecules transformations into cyclic precursors should be tried. The erythro-configurated acetylenic alcohol given below, for example, is disconnected into an acetylene monoanion and a symmetrical oxirane (M. A. Adams, 1979). Since nucleophilic substitution occurs with inversion of configuration this oxirane must be trens-conilgurated its precursor is commercially available trans-2-butene. 

All these intermediate complexes undergo various transformations such as insertion, transmetallation, and trapping with nucleophiles, and Pd(0) is regenerated at the end in every case. The regenerated Pd(0) starts the catalytic cycle again, making the whole process catalytic. These reactions catalyzed by Pd(0) are treated in Chapter 4. 

The reaction of alkenyl mercurials with alkenes forms 7r-allylpalladium intermediates by the rearrangement of Pd via the elimination of H—Pd—Cl and its reverse readdition. Further transformations such as trapping with nucleophiles or elimination form conjugated dienes[379]. The 7r-allylpalladium intermediate 418 formed from 3-butenoic acid reacts intramolecularly with carboxylic acid to yield the 7-vinyl-7-laCtone 4I9[380], The /i,7-titisaturated amide 421 is obtained by the reaction of 4-vinyl-2-azetidinone (420) with an organomercur-ial. Similarly homoallylic alcohols are obtained from vinylic oxetanes[381]. 

Acyi halides are reactive compounds and react with nucleophiles without a catalyst, but they are activated further by forming the acylpalladium intermediates, which undergo insertion and further transformations. The decarbonyla-tive reaction of acyl chlorides as pseudo-halides to form the aryipalladium is treated in Section 1,1.1.1. The reaction without decarbonylation is treated in this section. 

In addition to the catalytic allylation of carbon nucleophiles, several other catalytic transformations of allylic compounds are known as illustrated. Sometimes these reactions are competitive with each other, and the chemo-selectivity depends on reactants and reaction conditions. 

Allylic metal compounds useful for further transformations can be prepared by Pd-catalyzed reactions of allylic compounds with bimetallic reagents. By this transformation, umpolung of nucleophilic 7r-allylpalladium complexes to electrophilic allylmetal species can be accomplished. Transfer of an allyl moiety from Pd to Sn is a typical umpolung. 

Among several propargylic derivatives, the propargylic carbonates 3 were found to be the most reactive and they have been used most extensively because of their high reactivity[2,2a]. The allenylpalladium methoxide 4, formed as an intermediate in catalytic reactions of the methyl propargylic carbonate 3, undergoes two types of transformations. One is substitution of cr-bonded Pd. which proceeds by either insertion or transmetallation. The insertion of an alkene, for example, into the Pd—C cr-bond and elimination of/i-hydrogen affords the allenyl compound 5 (1.2,4-triene). Alkene and CO insertions are typical. The substitution of Pd methoxide with hard carbon nucleophiles or terminal alkynes in the presence of Cul takes place via transmetallation to yield the allenyl compound 6. By these reactions, various allenyl derivatives can be prepared. 

The most frequently encountered nucleophiles in functional group transformations are anions which are used as their lithium sodium or potassium salts If we use M to represent lithium sodium or potassium some representative nucleophilic reagents are... 

Representative Functional Group Transformations by Nucleophilic Substitution Reactions of Alkyl Halides... 

Section 8 1 Nucleophilic substitution is an important reaction type m synthetic organic chemistry because it is one of the mam methods for functional group transformations Examples of synthetically useful nucleophilic sub stitutions were given m Table 8 1 It is a good idea to return to that table and review its entries now that the details of nucleophilic substitution have been covered... 

These reactions are usually performed in water or alcohols as solvents and the alkox ide ion intermediate is rapidly transformed to an alcohol by proton transfer The other involves acid catalysis Here the nucleophile is often... 

Although the present chapter includes the usual collection of topics designed to acquaint us with a particular class of compounds its central theme is a fundamental reaction type nucleophilic addition to carbonyl groups The principles of nucleophilic addition to aide hydes and ketones developed here will be seen to have broad applicability m later chap ters when transformations of various derivatives of carboxylic acids are discussed... 

Substitution Reactions on Side Chains. Because the benzyl carbon is the most reactive site on the propanoid side chain, many substitution reactions occur at this position. Typically, substitution reactions occur by attack of a nucleophilic reagent on a benzyl carbon present in the form of a carbonium ion or a methine group in a quinonemethide stmeture. In a reversal of the ether cleavage reactions described, benzyl alcohols and ethers may be transformed to alkyl or aryl ethers by acid-catalyzed etherifications or transetherifications with alcohol or phenol. The conversion of a benzyl alcohol or ether to a sulfonic acid group is among the most important side chain modification reactions because it is essential to the solubilization of lignin in the sulfite pulping process (17). 

Cycloahphatics capable of tertiary carbocation formation are candidates for nucleophilic addition of nitriles. HCN in strong sulfuric acid transforms 1-methyl-1-cyclohexanol to 1-methyl-1-cyclohexylamine through the formamide (47). The terpenes pinene (14) [2437-95-8] and limonene [5989-27-5] (15) each undergo a double addition of HCN to provide, after hydrolysis, the cycloahphatic diamine 1,8-menthanediamine (16) (48). 

Nucleophilic Attack at Carbon or Hydrogen. Only the strongest of nucleophiles (eg, —NH2) can replace a hydrogen in pyridine. However, N-oxides and quaternary salts rapidly undergo addition, followed by subsequent transformations (12). 

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