Nitrone cycloaddition stereoselective cyclization

The convergence of the nitronate and nitrile oxide cycloadditions has allowed for the direct comparisons of yields and stereoselectivities of the two processes. For intramolecular reactions, the nitronate dipole typically required longer reaction times and/or elevated temperatures (22,98,135), however, the nitronate cycloaddition shows considerably higher diastereoselectivity (Table 2.42). Interestingly, the diastereoselectivity is dependent on the placement of a substituent on the tether. In the case of the silyl nitronate derived from 172, the diastereoselectivity is controlled by the substituent at C(l), while cyclization of the analogous nitrile oxide is governed by the substituent at C(l ) (Scheme 2.10) (124). 

Nitrile oxides are linear as opposed to nitrones which are planar with an approximately 120 C—N—O bond angle. Consequently, the cycloaddition transition states are rather different for these two dipoles. The nitrone usually, although not always, offers more promise of stereoselective cyclization the nitrile oxide can offer more promise of regiospecific cyclization, especially in forming 5,6-, 5,7- and larger fused bicyclic systems. 

N-donor ligand. The reaction appears to proceed via an acyclic iminoplatinum(II) intermediate that undergoes a subsequent intramolecular cyclization. Some mechanistic aspects of this versatile reaction have been elucidated.225,226 A4-l,2,4-oxadiazolines have been prepared by the [2+3] cycloaddition of various nitrones to coordinated benzonitrile in m-[PtCl2( D M SO)(PhCN)] precursors.227,228 Racemic and chiral [PtCl2(PhMeSO)(PhCN)] complexes have also been used in order to introduce a degree of stereoselectivity into the reaction, resulting in the first enantioselective synthesis of A4-l,2,4-oxadiazolines, which can be liberated from the complexes by the addition of excess ethane-1,2-diamine. 

Intramolecular cyclizations of silyl nitronates were also used in the preparation of aminosugars. In 2003 Kudoh et al. reported the stereoselective conversion of 2-nitroalkanols by silyl nitronate generation followed by an intramolecular nitronate-olefin [3 + 2] cycloaddition reaction (Scheme 51).88... 

Cyclization of nitrile oxides with a four-atom intervening chain to the alkene always leads to 5,6-fused bicylic isoxazolines possessing a bridgehead C—N double bond. This is in contrast to nitrone cycliza-tions where competition to form bridged bicyclic isoxazolidines is observed. The alkenyl oximes (73) and (74) cyclize in typical fashion via nitrile oxide intermediates (Scheme 21).33a>36 The stereochemistry of cyclization here was studied both experimentally and by calculation. The higher stereoselectivity observed with the (Z)-alkene is typical. (Z)-Alkenes cycloadd much slower than ( >alkenes in intermole-cular reactions this is attributed to greater crowding in the transition state. Thus, intramolecular cycloaddition of (Z)-alkenes depends on a transition state that is heavily controlled by steric factors. 

Denmark and co-workers also reported that the [4 -i- 2] cycloaddition of nitroalk-ene 172 with enol ether 173, as dienophile, in the presence of MAD proceeded at low temperatures to give the nitronate with two substituents on the C6 carbon (174) in 62 % yield on isolation. Because the cycloadduct 174 undergoes clean intramolecular [3 -I- 2] cycloaddition in xylene under reflux, in the presence of solid NaHCOs. This tandem cyclization strategy is a unique approach to the stereoselective synthesis of polyfunctionalized aminocyclohexane derivatives, as shown in Sch. 135 [174]. 

The Wittig-Horner olefination of the aldehyde 28 provided alkenes 29 which were subjected to radical cyclization leading to benzofused tricyclic j6-lactams 30, obtained as single diastereomers (Scheme 8) [36]. A convenient, direct regio- and stereoselective route to optically pure unusually fused or bridged tricyclic /3-lactams has been developed by the use of intramolecular nitrone-alkene cycloaddition reactions. For example, the aldehyde 21 can be transformed into nitrone 31 which subsequently was used for a variety... 

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