Nitroso dienophiles, cycloaddition

Streith J., Defoin A. Aza Sugar Syntheses and Multi-Step Cascade Rearrangements Via Hetero Diels-Alder Cycloadditions With Nitroso Dienophiles Synlett 1996 189-200... 

The precursor to (5) was made diastereoselectively by Fessner and coworkers [44]. When the intermediate ketose 1-phosphate was immediately submitted to hydrogenation conditions, l,5,6-trideoxy-l,5-imino-D-galactitol (1,6-dideoxygalactonojirimycin, 10) was obtained in fair yield [42]. The latter derivative was also obtained by a hetero Diels-Alder cycloaddition of a benzyloxycarbonyl nitroso dienophile to ( , )-sorbaldehyde dimethylacetal [45]. 

Lewis acid catalysis, apparently dispensible due to the very high reactivity of nitroso dienophiles, has not yet been investigated although such a study has been suggested by Streith and Defoin [8]. Thus, examples of asymmetric catalysis lack completely in this area of hetero Diels-Alder chemistry. Nevertheless, cycloadditions involving nitroso dienophiles have reached an advanced level concerning stereoselectivity and therefore much attention has been paid towards the preparation and application of chiral, enantiopure dienophiles and dienes for these reactions. 

An asymmetric Diels-Alder reaction of a chiral nitroso dienophile has been employed by Ganem et al. in order to open an elegant access to enantiomerical-ly pure (-t-)-mannostatin A 7-57 and several derivatives thereof [519], The cycloaddition of the heterodienophile 7-54 derived from mandelic acid to 1-me-thylthiocyclopentadiene 7-55 proceeded only in moderate diastereoselectivity, however, the desired product 7-56 was easily separated from its diastereomer. 

Carbamoyl nitroso dienophiles, derived from chiral pyrrolidines, have been generated and their reactivity with cyclohexa-diene investigated. Using (—)-fra/w-2,5-dimethylpyirolidine as the auxiliary, the [4 + 2] cycloadduct is isolated in 82% yield and with 98% diastereomeric excess (eq 10). Similarly, chiral ynamine dienophiles have been utilized in asymmetric [4 + 2] cycloadditions with a,p-unsaturated nitroalkenes to afford cyclic nitronic esters. The resulting esters subsequently undergo a rapid [1,31-rearrangement to afford chiral cyclic nitrones in moderate yield and high diastereoselectivity (eq 11)-... 

A unified picture of the mechanism of this cycloaddition for various structural types of nitroso dienophiles is not available. Depending upon the electronic and steric nature of the particular nitroso compound, the reaction apparently may vary from a concerted pericyclic process to one involving discrete dipolar intermediates. The net result of this mechanistic diversity is a few anomalous regiochemi-cal results in the cycloaddition. 

Brief reports of cycloadditions with chiral acyl nitroso dienophiles have recently appeared. - In one study, acyl nitroso compound (101) derived from the corresponding hydroxamic acid was added to cy-clohexadiene to afford a 3.5 1 mixture of diastereomeric adducts (102) and (103). It was proposed that dienophile (101) reacts in the cyclic chelated form shown, since the related methyl ether which cannot internally hydrogen bond shows much lower diastereoselectivity. ... 

Entry 3, Scheme 10.26) [52]. However, the use of an enantiopure mthenium salen complex (19) did not generate asymmetric induction, which suggests that the acyl nitroso dienophile intermediate readily dissociates from the chiral mthenium complex involved in the oxidation step prior to Diels-Alder cycloaddition. 

Enders, D., Meyer, O. Diastereo- and enantioselective Diels-Alder reaction of 2-amino-1,3-dienes. Liebigs Annalen 1996, 1023-1035. Streith, J., Defoin, A. Aza sugar syntheses and multi-step cascade rearrangements via hetero Diels-Alder cycloadditions with nitroso dienophiles. Synlett 996, 189-200. 

A novel pyrrole synthesis has been developed from 1,2-oxazines <05S3346>. The cycloaddition between nitroso dienophile 45 and 2,3-dimethylbutadiene gave 1,2-oxazine 46. Cleavage of the N-0 bond followed by an oxidative cyclization gave pyrrole 48. 

W-Acylsultams of glyoxylic acid 1.134 (R = CHO) and nitroso compound 1.134 (R = NO) are valuable dienophiles. Cycloadditions of 1.134 (R = CHO) with 1-methoxybutadiene mediated by Eu(fod)3 are highly selective [466] (Figure 9.36), and take place via a chelated complex. The reactions of the nitroso compound 1.134 (R = NO) with cyclopentadiene and cydohexadiene give useful results [467], though heterodienes 9.65 do not. The observed results ware interpreted in a fashion similar to that shown in Figure 9.32. 

Arylnitroso compounds of various types react with both electron-rich and electron-deficient dienes under mild conditions (usually 0-l(X)°C) to produce dihydrooxazines. As mentioned in the preceding section, Kresze s group has looked in considerable detail at orientational preferences and kinetics of [4 + 2] cycloadditions with various phenylnitroso compounds and substituted 1,3-dienes. Table 3-1 contains some of the results of cycloadditions of aromatic nitroso dienophiles with representative unsymmetrical 1- and 2-substituted dienes." Scheme 3-1 shows the subtle regiochemical trends that can be observed in a series of these reactions. These results were rationalized based on consideration of putative dipolar and nonpolar transition states and their relative stabilization by aromatic electron-donating and -withdrawing substituent groups. 

Work has recently appeared on the synthesis and cycloaddition reactions of vinylnitroso compounds. - Although these compounds are capable of acting either as heterodienes or as nitroso dienophiles, their reactivity is critically dependent on their structure. In general, if the vinylnitroso system contains any )8 substituents, the compounds will react as dienophiles if there is no /3 substituent, the system prefers to act as the 4tt component of a Diels-Alder reaction and will react with dienophiles. 

In general, most types of C-nitroso compounds appear to be reactive heterodienophiles. On the other hand, JV-nitroso compounds and nitrosyl chloride do not usually undergo [4 + 2] cycloadditions.1 Much of the early work in this area can be found in the Hamer and Kresze reviews, which cover the literature through 1967.,a b This chapter will emphasize newer aspects of [4 + 2] cycloadditions involving nitroso dienophiles. 

Intramolecular cycloaddition reactions with nitroso dienophiles have been used in a number of syntheses of alkaloids. For example, cycloaddition of the acyl nitroso compound formed from the hydroxamic acid 31 gave the dihydro-oxazine 32, which was converted to the alkaloid gephyrotoxin 223AB (3.31). ... 

Recently, Sherburn and coworkers reported interesting results on the HDA cycloaddition of parent [3]-[8]dendralenes with nitroso dienophiles and its application to a synthesis of branched aminosugars [32]. Scheme 2.21 depicts selected results of the full sequential DTHDA cycloadditions of parent [3]dendra-lene, 127 and [4]dendralene, 125, with nitroso dienophiles. [4]Dendralene 125... 

The normal demand hetero Diels-Alder cycloaddition between nitroso reagents 171 and dienes 172 leads to the formation of 3,6-dihydro-1,2-oxazines 173 via the concomitant stereoselective formations of a C—N and a C O bonds (Scheme 41.36). Several nitroso dienophiles like the a-chloronitroso, arylnitroso, or acylnitroso compounds are known to react efficiently in cycloadditions. Chiral nonracemic chloronitroso and acylnitroso compounds have been developed to achieve diastereoselective nitroso Diels-Alder reactions, and recently Yamamoto and co-workers reported on the first enantioselective-catalyzed cycloaddition with a pyridylnitroso dienophile. ° ... 

The synthetic potential of the tandem [4+2]/[3+2] cycloaddition process is greatly enhanced by the employment of vinyl ether dienophiles. For example, the use of vinyl butyl ether as a dienophile leads to a tricyclic nitroso acetal, which gives a tricyclic lactam, as shown in Eq. 8.113. 

The third member of the tandem inter [4+2]/intra [3+2] cycloaddition family is classified as the bridge mode, in which the dipolarophile is attached to the dienophile. Simple, 1,4-pentadi-enes as well as 2-alkoxy-l,4-pentadienes can function effectively as dienophiles and dipolarophile combinations with excellent chemical selectivity and regio- and diastereoselectivity. Hydrogenation of the bridged nitroso acetals produces hydroxymethylated derivatives in high diastereo- and enantioselectivity (Eq. 8.116).185... 

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