Cycloaddition dipolar intramolecular, stereospecific

Aldoximes, tautomeric cycloaddition, 1,3-dipolar, intramolecular, stereospecific with - 44, 663 Aliquat 336... 

Pyranopyrroloimidazoles have been prepared stereospecifically by an intramolecular 1,3-dipolar cycloaddition reaction. Either enantiomer of the imidazoline derivative 176 (the -enantiomer is shown) may react with the bromoacetyl-containing acrylate dipolarophile 177, in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene (DBU), to give the diastereomerically pure tricyclic product 178 in moderate yield (Equation 15). This reaction involves quaternization of the imidazole N, reaction of the quaternary salt with base to give the 1,3-dipole, which can then react, intramolecularly and stereospecifically, with the tethered dipolarophile <1997TL1647>. 

The application of intramolecular dipolar cycloaddition reactions to the synthesis of complex natural products has recently come to be recognized as a very powerful synthetic tool, one equally akin to the intramolecular Diels-Alder reaction in its potential scope of application.69 This is particularly the case with nitrile oxides and the 1NOC reaction has been extensively utilized in total synthesis.70 The intramolecular nitrile oxide cycloaddition (INOC) generally displays exceptional regio- and stereo-chemical control which undoubtedly accounts for the popularity of this reaction. Internal cycloadditions of nitrile oxides have been found to offer a powerful solution to many problems in complex natural product synthesis.48 For example, Confalone and coworkers have utilized the INOC reaction for the stereospecific synthesis of the key amino alcohol (60), which was converted in five subsequent steps to ( )-biotin (61 Scheme 14).71... 

An intramolecular [3 + 2] dipolar cycloaddition reaction has also been exploited in the design of a concise, stereospecific synthesis of ( )-a-lycorane (57) (119). Thus, cyclization of the azomethine ylide 145, which was produced in situ by the reaction of 144 with IV-benzylglycine, in refluxing toluene furnished the cw-hydroindole 146 as the exclusive product (Scheme 14). The transformation of 146 to racemic a-lycorane (57) was then achieved by N-debenzylation via catalytic, transfer hydrogenation and subsequent Pictet-Spengler cyclization. 

An intramolecular allyl silane/N-sulfonyl iminium ion cyclization has also been used as a pivotal step in an approach to the tricyclic core of the unique marine alkaloid sarain A [46]. The starting material was aziridine ester 129 (Scheme 25) which was elaborated to amide 130. An important step in the synthetic strategy was thermolysis of 130 to an azomethine ylide, which underwent stereospecific intramolecular 1,3-dipolar cycloaddition with the Z-alkene to produce bicyclic lactam 131 [47]. This compound was then elaborated into allyl silane 132. It was then possible to replace the lactam N-benzyl functionality with a tosyl moiety, leading to 133, and subsequent reduction of the carbonyl group afforded the desired cyclization precursor a-hydroxy sulfonamide 134. Exposure of 134 to ferric chloride promoted cyclization to a single stereoisomeric tricyclic amino alkene 136 having the requisite sarain A nucleus. It is believed that the intermediate N-sulfonyl iminium ion cyclizes via the conformation shown in 135. 

Stereospecific intramolecular 1,3-dipolar cycloaddition with tautomeric aldoximes generated in situ... 

Wang JC, Krische MJ (2003) Intramolecular Organocatalytic [3t-2] Dipolar Cycloaddition Stereospecific Cycloaddition and the Total Synthesis of (t-/-)-Hirsutene. Angew Chem Int Ed 42 5855... 

Phosphine-Catalyzed Reactions Phosphine-catalyzed [3+2] dipolar cycloaddition has been applied in an intramolecular manner, whereby three contiguous stereogenic centers, including a quaternary center, are created in a single operation (Scheme 6.27). It may be noted that the intramolecular cycloaddition is stereospecific. When the E-isomer is used as the starting material, the quaternary center formed possesses the stereochemistry consistent with the structural features of hirsutene [31]. 

Wang, J.-C., Krische, M. J. (2003). Intramolecular organocatalytic [3-1-2] dipolar cycloaddition stereospecific cycloaddition and the total synthesis of ( )-hirsutene. Angewandte Chemie International Edition, 42, 5855-5857. 

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