5-Alkylation intramolecular

A tandem palladium-catalysed ort/io-alkylation/intramolecular Heck reaction coupling sequence was used effectively to access in fair yields the tetrahydro 1-benzoxepines 67 from the iodoaryl precursor 66 and the appropriate alkyl bromide. The norbornene plays a relay role in the proposed reaction cycle <06JOC4937>... 

Intramolecular Alkylations. Intramolecular spiroalkylation of the suitably functionalized 5(477)-oxazolone 188 produced 189 in good to excellent yield. Acid hydrolysis of 189 then gave the cyclic amino acid 190 required in the synthesis of the aldose reductase inhibitor sorbinil (Scheme 7.57). ... 

The mechanism of this unusual cis addition has not been clarified. The bromoethyl derivative 2 can be further alkylated (intramolecularly) to give the deuterated cyclopropyl derivative 3. Once again, cis addition predominates, with 46% de. Upon hydrolysis of the cyclopropyl derivative, optically active (V)-l-amino-cyclopropane-2-r/2-l-carboxylic acid (4) in 44% yield and 46% ee is obtained. 

Alkylation with aldehyde 107 Alkylation, enantioselective 165 Alkylation, intramolecular 134,167 Enantioselective Mannich 151 From alcohol 26,41,86,176 From amide 11, 109,163 Halogenation, enantioselective 158... 

Likewise, Lautens and coworkers have demonstrated the strength of the concept of sequential alkylation-alkenylation by application to the synthesis of fused aromatic rings. Hence, in the presence of 10% of Pd acetate, 20% of tri-2-furylphosphane, two equivalents of norbornene, and two equivalents of cesium carbonate, bromoenoates and related derivatives, ortho-substituted aryl iodides react in boiling acetonitrile in the sense of a Pd-catalyzed ortho-alkylation-intramolecular Heck reaction to furnish fused aromatic carbocy-cles 47-53 in moderate to excellent yields (Scheme 17) [74]. 

Other applications of this method include, e.g. the synthesis of the antibiotic A26771B (5i) [118] and the marine cembranolide isolobophytolide [119], Trost and Warner [120] reported that a-sulfonyl sulfones can also serve as the substrates of ir-allylpalladium complexes for macrocyclization. Furthermore, an a-hydroxy-carbonyl ketone was alkylated intramolecularly by a a-allylpalladium complex in the total synthesis of the macrocyclic sesquiterpene humulene [121]. 

Ito and coworkers [122] found that allylsulfides can be alkylated intramolecularly by epoxides in the presence of a proper base to form macrocycles. Tsuji and... 

Cyclopentenone annelation. Enolates condense with 1 in an alkylation-intramolecular Wittig reaction sequence to afford cyclopentenones (yields, 14-39%). 

Routes Employing Late-Stage Bond Formation to C-1 A one-pot N-alkylation/intramolecular conjugate addition/cyclization sequence of reactions between methyl 7-iodohept-2-ynoate (1348) and the chiral amine 1349 was the starting point in the synthesis of (—)-lasubine II (1342) by Ma and Zhu (Scheme 168). The reaction, carried out in... 

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