Base-assisted intramolecular

In 2001, 3-unsubstituted 4-alkyl-4-carboxy-2-azetidinones have been reported to be prepared by base-assisted intramolecular alkylation of /V-benzvI -/V-chloroacetyl amino acid derivatives [180]. /V-benzyl or /V--methoxvbenzvI) amino acid derivatives in THF, treated with propylene oxide and chloroacetyl chloride afforded the /V-chloroacetyl amino acid derivatives. The treatment of the latter in CH3CN with CS2CO3 (or NaH) produced the intramolecular cyclization of 4,4-disubstituted (3-lactams, (Scheme 81). 

Scheme 81 Synthesis of 4,4-disubstituted [3-lactams by base-assisted intramolecular alkylation...

Scheme 2.114 Base-assisted intramolecular transesterification of phosphites.

In 2005, a base-assisted intramolecular [5+2] cycloaddition of 6-acetoxy-3-pyranones with alkynes was reported by Celanire et al. [72]. As depicted in Scheme 20.30, the treatment of 6-acetoxy-3-pyranones 70a,b with a stoichiometric amount of TEA as a base in refluxing toluene provided the corresponding similar cycloadduct 71a in good yield, since the sUyl derivative 70b underwent conversion to 71a via a desilylation process. The use of acetonitrile instead of... 

Microwave-assisted intramolecular C - N bond formations have also been studied. Substituted benzimidazoles were easily prepared from the corresponding M-(2-bromophenyl)imidoformamides by Brian et al. (Scheme 102) [ 104]. The protocol involved the use of a combination of Pd2 (dba)3 and PPha in a mixture of DME and water using NaOH as the base at 160 °C. It was apphca-ble for electron poor, neutral and rich as well as sterically hindered amidines. The fastest reactions were obtained with an electron withdrawing substituent... 

Addition of such a-lithiosulfinyl carbanions to aldehydes could proceed with asymmetric induction at the newly formed carbinol functionality. One study of this process, including variation of solvent, reaction temperature, base used for deprotonation, structure of aldehyde, and various metal salts additives (e.g., MgBrj, AlMej, ZnClj, Cul), has shown only about 20-25% asymmetric induction (equation 22) . Another study, however, has been much more successful Solladie and Moine obtain the highly diastereocontrolled aldol-type condensation as shown in equation 23, in which dias-tereomer 24 is the only observed product, isolated in 75% yield This intermediate is then transformed stereospecifically via a sulfoxide-assisted intramolecular 8, 2 process into formylchromene 25, which is a valuable chiron precursor to enantiomerically pure a-Tocopherol (Vitamin E, 26). 

These effects are minimized for n-o fragmentations, especially those where the intramolecular electron transfer takes place between spatially adjacent orbitals. Somewhat related stereoelectronic considerations apply to nucleophile or base assisted fragmentations where certain three-dimensional dispositions of existing bonds may favor the assistance, in a way related to, for example, the anti stereochemistry of elimination reactions (Sect. 5.2). 

If we now concentrate our attention on cyclopentenone V and compare this product with IV it will be obvious that another intramolecular aldol condensation between the cyclooctanone ketone and the angular carbon j8 to the cyclopentenone keto function will suffice to convert IV into V, with the proper stereochemistry. The required nucleophilic character of the carbon involved there would be derived from the base assisted proton abstraction in a kinetic fashion... 

Attack as a Nucleophile. In the Cu(II)-catalyzed hydrolysis of the acetyl ester of 2-pyridinecarboxaldoxime, the metal-bound water molecule makes nucleophilic attack at the carbonyl carbon of the bound ester (H), instead of the kinetically equivalent attack by an external water molecule at the ester linkage bound by the metal ion (43). The basicity and nucleophilicity of water would decrease upon coordination to metal ions. Efficient nucleophilic attack by the Cu(II)-bound water in H is attributable to the general base assistance from another water molecule and to the efficient intramolecular reaction between the nucleophile and the ester. 

Intramolecular Mizoroki-Heck reactions with styrene-type alkenes constitute the second frequently met case. Finding suitable rationales in theses cases seems to be more intricate. There is some evidence for a mechanism involving a radical intermediate [11]. Most explanations, however, cite a facile epimerization at the benzylic position and, thus, furnishing the required cw-stereochemistry or a base-assisted reductive elimination of the palladium species (Scheme 6.3) [11]. In some cases, suitable substrates or conditions can lead to the a r/-elimination products via an Elcb-type mechanism [23,24]. 

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