Nucleophiles heteroatom-based

Most of the reactions which will be discussed lead to carbonyl compounds with a stereogenic center in the 3-position. This is illustrated in Scheme 1 a substrate molecule (1 X = heteroatom or heteroatom-based functional group), having an electron-deficient double bond, is attacked by a nucleophilic reagent (possibly in the presence of a coordinating ligand or a catalyst) to form an anionic intermediate (2), which is then converted to the product (3) on hydrolytic work-up. 

Similar to the epoxides, the most frequently encountered synthetic transformation for aziridines is nucleophilic ring-opening, whereby carbon- and heteroatom-based nucleophiles are comparably important. As an example of the former type, aziridine-2-carboxylates 100 can be ring-opened with higher order cuprates to give the protected amino acid derivatives 101, corresponding to attack at the less-substituted aziridine carbon [95TL151],... 

There is, of course, no paucity of examples using heteroatom-based nucleophiles. For example, aziridine-2-/-butyl carboxylate 102 reacts with primary amines to give the dialkylated diamino-propionic acid derivatives 103, which are interesting precursors for the synthesis of cyclosporin analogs. Again, attack occurs overwhelmingly at the B-carbon [95TL4955]. 

A wide range of heteroatom-based nucleophiles, and cyanide, react with 2-, 3-, and 4-halopyridines in minutes at elevated temperature in polar solvents such as HMPA, DMSO, or A -methylpyrrolidine (NMP) under microwave irradiation (e.g., Scheme 102) <2002T4931>. Aminations of halopyrimidines are likewise greatly accelerated in this way, e.g., <2004TL757>. 

Hydroxymethylaziridine 67 undergoes ring opening in the presence of either carbon- or heteroatom-based nucleophiles upon treatment with 2 equiv of potassium hydride to provide the t)7aminoalcohol derivative 69. The key step of the reaction is considered to be an aza-Payne rearrangement of the deprotonated aziridine methanol to the... 

Carbohydrates are excellent substrates to test nucleophilic displacement reactions with a variety of heteroatom-based nucleophiles. These reactions can be tried on primary and secondary hydroxyl groups at different sites of the sugar ring, and with different steric or stereoelectronic dispositions [1]. 

Z Heteroatom lone pairs as nucleophiles RS- r CN- RO- Softer anions are more nucleophilic. If same atom, more basic, more Nu Substitutions Additions. Nucleophile vs. base decision See allylic sources... 

An allylic electron source can be considered to be a vinylogous lone pair. Sometimes the lone pair itself is the nucleophile and can undergo reactions similar to the lone pair sources in the first column of the matrix. However, most often the nucleophile is the end carbon atom of the pi bond. The heteroatom lone pair is much harder than the pi bond, and the decision of which to use as the nucleophile is based on the hardness of the electrophile (HSAB principle) and will be discussed at greater length in Section 9.4. 

The majority of N-heterocyclic carbenes and their metal complexes are obtained from cyclic azolium derivatives (Fig. 8). Nevertheless, the first complex with a heteroatom stabilized carbene ligand, although it was not recognized as such, was prepared by Tschugajeff et al. as early as 1925 [157]. It was later identified as a heterocarbene complex [158]. Tschugajeff reacted the nucleophilic proton base... 

In principle, the nucleophilic attack at alkene or alkyne ligand can be a reversible process, like the reaction of carbonyl ligand. The reversibility often has been confirmed in the reaction of heteroatom-based nucleophiles, but carbon nucleophiles rarely undergo the reversible ahack at alkenes and alkynes [30]. Occurrence of an equilibrium reaction was observed between the combination of alkene-metal complex with amine on one hand, and zwiher ionic adduct made from the former combination on the other (Eq. 8.6) [31,32]. The isolation of the latter adduct was also realized in some cases as described later. It was demonstrated that this type of reversible adduct formation did not accompany E-Z isomerization of the alkene, meaning stereospecihc nature of the C-N bond formation and its reverse. A closely related stereochemical analysis demonstrated that the ahack of the amine at the coordinated alkene takes place from the side opposite to the metal atom, as will be discussed later in more detail. 

Kang and co-workers have reported reactions of open-chain vinyl-substituted cyclic carbonates with many stabilized and nonstabilized carbon nucleophiles,heteroatom nucleophiles, hydride equivalent,and vinyl and aryltin reagents. Retention of configuration has been observed for malonate, for thiophenolate, and for the conjugate base of phthalimide. In the absence of nucleophile a proton elimination ensues (Scheme 44). The reaction with iodobenzene produces a reductive ring opening by a variant of the Heck reaction. ... 

A list of common DMGs classified as carbon-based and heteroatom-based DMGs is shown in Table 26.2. DMGs generally provide nseful functionality for further transformation. A good DMG must be a good coordination site bnt a poor electrophile to prevent nucleophilic attack by the base. 

Conjugate Addition. TBDMS triflate has been used to promote the conjugate addition of carbon- and heteroatom-based nucleophiles to a range of a./S-unsaturated carbonyl compounds, in both stoichiometric and catalytic quantities. In some cases, the silyl enol ether is isolated, in other cases, it is implied as an intermediate but hydrolyzed either in situ or by addition of an acid or a reagent known to cleave a carbon-silicon bond e.g., TBAF. Examples of carbon-based nucleophiles are shown in eqs 22-26. 

In the last few years, the use of NHC-Cu complexes in catalysis has grown exponentially, particularly for the transfer of carbon and heteroatom-based nucleophiles to various electrophilic substrates. Copper-catalyzed boron and silicon transfers have recently been reported, thus expanding the scope of NHC-copper-catalyzed reactions. Notably, the design of new chiral NHC ligands has enabled the successful development of efficient C-C and C-H bond forming enantioselective reactions. 

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