Synthetically important reactions

This aldehyde is a key intermediate in the synthesis of the Inhoffen-Lythgoe diol, which is one possible precursor to vitamin D and its derivatives [21], The aldehyde could not be formed by pyrolysis of the corresponding ester in decalin at 95 C. Other procedures that accomplished the rearrangement required heating in excess of 220°C [22]. 

Another important example of the use of an aqueous medium to effect the Claisen rearrangement is the formation of the aldehyde below from the vinyl ether precursor in the synthesis of aphidicolin. This reaction was accomplished upon heating in 2.5 1 water-methanol solutions at 80°C for 24h [20]  

Previous efforts by McMurry accomplished the same conversion by heating the vinyl ether, with the diol protected as the acetonide, at 220°C in a base-washed silylated sealed glass tube containing toluene and sublimed sodium t-pentoxide, but the yield was lower, 60% [23]. 

Nearly simultaneous with reports of the aqueous-solution Claisen rearrangement from the Grieco group was a publication from Broka revealing the Claisen rearrangement of the following vinyl ether [25]  

Another example of a striking rate acceleration in a Claisen rearrangement conducted in water is that of 6-P-glycosylallyl vinyl ether  

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The best characterized of these reactions involve the mercuric ion, Hg ", as the cation. The same process occurs for other transition-metal cations, especially Pd, but the products often go on to react fiirther. Synthetically important reactions involving Pd will be discussed in Section 8.2 of Part B. The mercuration products are stable, and this allows a relatively uncomplicated study of the addition reaction itself The usual nucleophile is the solvent, either water or an alcohol. The tenn oxymercuration is used to refer to reactions in... 

The a-sulfenylation138 and a-selenenylation139 of carbonyl compounds are synthetically important reactions, particularly in connection with the introduction of... 

In contrast to the transition metals, where there is often a change in oxidation level at the metal during the reaction, there is usually no change in oxidation level for boron, silicon, and tin compounds. The synthetically important reactions of these three groups of compounds involve transfer of a carbon substituent with one (radical equivalent) or two (carbanion equivalent) electrons to a reactive carbon center. Here we focus on the nonradical reactions and deal with radical reactions in Chapter 10. We have already introduced one important aspect of boron and tin chemistry in the transmetallation reactions involved in Pd-catalyzed cross-coupling reactions, discussed... 

Another interesting facet of the question of tautomerism is that, under mild conditions for trimethylsilylation, succinic anhydride will enolize twice thus producing the bis(trimethylsilyi) derivative of furan-2,5-diol (80TL3423). Whether aromatization can be held to promote this synthetically important reaction remains unclear since butenolides and even butanolides react in a similar fashion (74JOC2558, 79BCJ1953). 

A characteristic and synthetically important reaction of ethyne and 1-alkynes is salt ( acetylide ) formation with very strong bases. In such reactions the alkynes behave as acids in the sense that they give up protons to suitably strong bases ... 

This synthetically important reaction is known as the Sakurai or Hosomi-Sakurai reaction149. The intramolecular Sakurai reaction is useful for the synthesis of spiro (125) and fused (126) ring systems, as shown in equations 82 and 83150. 

Exchange involving boron-halogen bonds and boron-oxygen bonds has been observed in the synthetically important reactions for the preparation of alkyldihaloboranes from alkylboroxines and boron trihalides (165, 167, 169). 

The three-part Figure 2.31, with a hst of synthetically important reactions, shows the various nucleophiles that can he alkylated via SN2 reactions. This list refers to alkylations with alkyl... 

Synthetically important reactions employing transition metal carbonyl complexes see Carbonyl Complexes of the Transition Metals) have been extensively developed and applied in total synthesis of complex organic molecules. Stoichiometric amounts of metal carbonyl complexes are usually employed, but the often significant increase in complexity going from starting material to product and the... 

Cleavages of metal- or nonmetal-N bonds by D O or ROD yield N—D bonds, although these are seldom synthetically important. Reactions of primary or secondary amines can produce mixed hydro - deuterio products ... 

The electron donating ability of amines, has been utilized in several photochemical reactions for the generation of reactive radical ions which can subsequently undergo synthetically important reactions. 

Sulfenes are very reactive and occur as intermediates in several synthetically important reactions (see p. 115).3b They have not been isolated and are formed by base-induced eliminations for instance, a sulfene is formed in the reaction of a sulfonyl chloride containing at least one a-hydrogen atom with a tertiary amine. As an illustration, when phenylmethanesulfonyl chloride (97) is treated with pyridine, phenylsulfene (98) is formed as a transient species (Scheme 65). 

Electrophilic addition reactions of carbenes to cyclopropane structures are rare and not synthetically important. Reaction of carbenes with bicyclo[2.1.0]pentane generally gave products arising from C —H insertion at one of the methylene groups of the four-membered ring. ° An exception was difiuorocarbene which gave 1,1-difluorohexa-l,5-diene (2) in very low yield by cleavage of two C —C bonds. - ... 

The hetero [2+2] cycloaddition reaction is a synthetically important reaction for the construction of 4-membered heterocyclic compounds. As far as the catalytic asymmetric reaction is concerned, however, only the cycloaddition between ketenes and aldehydes has been reported. The thus synthesized chiral oxetan-2-ones are employed as monomer precursors for the biologically degradable co-polyesters and also as chiral building blocks for natural product synthesis. Two types of catalysts. Cinchona alkaloids and a chiral Lewis acid, are known to promote this reaction. 

The followings are some synthetically important reactions where reductive process is involved (Scheme 96) [241-243]. 

The cationic intermediates also can be captured by solvent. Halogenation with solvent capture is a synthetically important reaction, especially for the preparation of chlorohydrins and bromohydrins. Chlorohydrins can be prepared using various sources of electrophilic chlorine. Chloroamine T is a convenient reagent for chloro-hydrin formation. Bromohydrins are prepared using NBS and an aqueous solvent mixture with acetone or THF. DMSO has also been recommended as a solvent. These reactions are regioselective, with the nucleophile water introduced at the more-substituted position. 

The carbonyl group is one of the most prevalent of the functional groups and is involved in many synthetically important reactions. Reactions involving carbonyl groups are also particularly important in biological processes. Most of the reactions of aldehydes, ketones, esters, carboxamides, and the other carboxylic acid derivatives directly involve the carbonyl group. We discussed properties of enols and enolates derived from carbonyl compounds in Chapter 6. In the present chapter, the primary topic is the mechanisms of addition, condensation and substitution reactions at carbonyl centers. We deal with the use of carbonyl compounds to form carbon-carbon bonds in synthesis in Chapters 1 and 2 of Part B. 

Dihydroisoxazoles display characteristic and synthetically important reactions. 

Co2Rh2(CO)i2] and [Co3Rh(CO)i2] catalyze the hydrosilation of isoprene, cyclohexanone, cyclohexenone, and 1-alkynes, the regioseleetive inter- or intramolecular (Eq. 5) silylformylation of alkynes and 1-alkynals, and the silylcarbo-cyclization of enynes, diynes, and alkynals. These synthetically important reactions have been reviewed recently. 

Oxidative iodination of aromatic compounds by the combination of a hypervalent iodine reagent with iodine is a synthetically important reaction (Section 3.1.4) [34]. Polymer-supported diacetate 4 is a particularly convenient reagent for oxidative iodination since it can be regenerated and reused many times. Reagent 4 gives the best results for the iodination of electron-rich arenes 13, with predominant formation of the para-substituted products 14 (Scheme 5.8) [12,21]. 

This chapter is concerned with reactions that introduce or interchange substituent groups on aromatic rings. The most important group of such reactions are the electrophilic aromatic substitutions, but there are also significant reactions that take place by nucleophilic substitution mechanisms, and still others that involve radical mechanisms. Examples of synthetically important reactions from each group will be discussed. Electrophilic aromatic substitution has also been studied in great detail from the point of view of reaction mechanism and structure-reactivity relationships these mechanistic studies received considerable attention in Part A, Chapter 9. In this chapter, the synthetic aspects of electrophilic aromatic substitutions will be emphasized. 

Reduction of nitro compounds to amines is a synthetically important reaction (98) and is practiced since the birth of modern chemical industry—many aromatic amines are key intermediates in production of dyes and pesticides. However, the stoichiometric reductions using iron or alkali metal hydrogen sulfides or catalytic hydrogenations with heterogeneous catalysts leave room for improvements in selectivity, especially with reference to halonitro-derivatives. There are many homogeneous catalysts such as the rhodium carbonyls in the presence of amines or chelating diamines, or [Rus(CO)i2] in basic amine solutions that are... 

We have uncovered seven synthetically important reactions in this chapter so far. We can (1) brominate and (2) chlorinate benzene. We can (3) nitrate and reversibly (4 and 5) sulfonate benzene. The two Friedel-Crafts reactions (6 and 7) allow the construction of carbon-carbon bonds to give some alkyl benzenes and give you another synthetic route to compounds containing carbon-oxygen double bonds. Figure 14.48 summarizes the situation. 

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