Nitrile oxides, alkenyl

The cycloaddition of nitrile oxides RCNO (R = alkyl, alkenyl, aryl), generated in situ from either RCH2NO2/PI1NCO or RCH=NOH/NaOCl to (R)-( + )-limonene, proceeds regioselectively at the extracyclic double bond, but not stereospecifically, to form (5R/S )-isoxazoles 78 in 64% to 81% isolated yield (241). 

TABLE 6.13. STEREOSELECTIVITY IN INTRAMOLECULAR CYCLOADDITIONS WITH a-CHIRAL NITRILE OXIDES AND C-, 0-, OR S-CONTAINING ALKENYL CHAIN... 

Intramolecular cycloadditions of alkenyl-substituted nitrile oxides produce bicyclic isoxazolines. When monocyclic olehns are used, tricyclic structures are obtained. This approach was pioneered by both Kozikowski s and Curran s groups. A typical case involves the cycloaddition of nitro compound 191 [mixture of diastereomers derived from pentenose pyranoside 190], which produced a diaster-eomeric mixture of isoxazolines that contain cis-fused rings (i.e., 192) in near quantitative yield (326) (Scheme 6.85). Further elaboration of this mixture led to epoxycyclopentano-isoxazoline 193, which was then converted to the aldol product in the usual manner. The hydrogenation proceeded well only when rhodium on alumina was used as the catalyst, giving the required p-hydroxyketone 194. This... 

The use of alkenyl nitrile oxides is an effective method for the construction of bland polycyclic isoxazolines (2,4,200,236,237). Due to the rigid linear structure of the nitrile oxide, the reaction of alkenyl nitrile oxides almost always proceeds to give bicyclo[X,3,0] derivatives for X = 3-5. Most frequently, the diastereoselec-tivities are controlled by a chiral center on the link between the alkene and the dipole groups. 

For alkenyl nitrile oxides having the alkene in a cyclic structure, such as compound 141, high diastereoselectivities can be obtained (Scheme 12.47). Compound 141 is formed in situ, and undergoes a spontaneous cyclization to furnish 142 as the sole diastereomer. Toyota et al. (239) used the tricyclic isoxazoline 143 in the synthesis of (+)-pumiliotoxin C. 

For intramolecular 1,3-dipolar cycloadditions, the application of nitrones and nitrile oxides is by far most common. However, in increasing frequency, cases intramolecular reactions of azomethine ylides (76,77,242-246) and azides (247-259) are being reported. The previously described intermolecular approach developed by Harwood and co-workers (76,77) has been extended to also include intramolecular reactions. The reaction of the chiral template 147 with the alkenyl aldehyde 148 led to the formation of the azomethine ylide 149, which underwent an intramolecular 1,3-dipolar cycloaddition to furnish 150 (Scheme 12.49). The reaction was found to proceed with high diastereoselectivity, as only one diaster-eomer of 150 was formed. By a reduction of 150, the proline derivative 151 was obtained. 

The entropically enhanced cycloaddition rate of an intramolecular cycloaddition permits alkenyl nitrile oxides to cyclize in the presence of free amino groups, in contrast to intermolecular reactions. Since nitrile oxides have a wide spectrum of possible intermolecular reactions, they also react well in macro-cyclic cyclizations. 

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. 

The reaction sequence of most interest in this route is the conversion of 4 into 3 (Scheme 15.4). Presumably, the NaOCl that is present in the reaction mixture chlorinates the deprotonated oxime nitrogen to create an iV-chloro-nitrone 9 which then eliminates HC1 to generate the alkenyl nitrile oxide 10. The latter then undergoes the anticipated 1,3-dipolar cycloaddition reaction to form 3. 

The same salt from acetylene afforded similarly adducts with furan and 1,3-diphenyl i sobenzofuran. A number of alkynyl iodonium salts underwent also [2 + 3] cycloaddition with dipolarophiles such as a-diazocarbonyl compounds, nitrile oxides, etc., allowing the preparation of iodonium salts with an alkenyl or a heterocyclic moiety [7],... 

Componds such as (25) have been prepared in high yield by linking c/o.ro-C2Bio-clusters with nitroimidazoles the precursors are m-alkenyl and (U-alkynyl-2-nitroimidazoles and carbaborane nitrile oxide. The lipophilic nature some of the new conqtlexes has been noted. Aminoalkyl-derivatives of C/050-C2B10H12 have been reported. The functional groups allow the carbaboranes to be incorporated into structures that are of potential use in BNCT. A range of other functionalised carbaborane clusters have been prepared for example, the attachment of... 

J641 9 CycloadditiorK and Other Additions to Alkenyl-, Alkynyl- and Dienyl Boronic Esters 9.3.S.2 Nitrile Oxides... 

Scheme 7.12 Proposed mechanism for ruthenium-catalyzed oxidative alkenylation and cyclization of aromatic nitriles.

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