Nitroso-Diels-Alder reactions

The 4 + 2-cycloaddition of 2-substituted 1,2-dihydropyridines with nitrosoben-zene produces [2.2.2]bicycloadducts, which are readily reduced by alane to trans-2-substituted 3-amino-l,2,3,6-tetrahydropyridines stereospeciflcally.123 The intramolec- (g) ular nitroso-Diels-Alder reaction of a-acetoxynitroso derivatives in aqueous medium produces 3,6-dihydro-l,2-oxazines in high yield.124 The nitroso-Diels-Alder reaction of acyclic OTIPS-dienes (115) and 6-methyl-2-nitrosopyridine (114) in the presence of (g) [Cu(MeCN)4(difluorosegphos)]PF6 yielded the dihydro 1,2-oxazine cycloadduct (116) with high yield and enantioselectivity (Scheme 33). 125 (Fe)... 

Alder reaction [524, 525]. Danishefsky et al. have used nitroso dienophiles for the synthesis of mitomycin K and antibiotics of the FR 900482 family, the latter ones are structurally unique aziridino-l,2-oxazine derivatives [526-529]. An approach directed to the cephalotaxus alkaloids has been worked out by Fuchs et al. [530], and several indolizidine alkaloids have been prepared by Keck s [531] and Kibayashi s groups [532,533]. Kibayashi et al. also synthesised Nuphar piperidine alkaloids in enantiomerically pure form by means of an asymmetric nitroso Diels-Alder reaction [534]. 

Kresze and cowoikers have used nitroso Diels-Alder reactions in synthesis of a variety of inosamines and related compounds. One example of this work is the synthesis of conduramine-Fl (92) as shown in equation (34). In this case, diene (91) reacted with a-chloro nitroso cyclohexane to afford adduct (91) as the only product. Just why this stereoisomer was formed is not obvious. Compound (91) could be converted to the conduramine in a few steps. 

In a series of interesting pqrers, Kresze has explored chiral nitroso Diels-Alder reactions. Several different chiral a-chloro nitroso substrates have bron examined and mannose derivative (93) proved to be one of the best auxiliaries. This dienophile is very reactive with both cyclic and acyclic dienes, affor-... 

Intramolecular acyl nitroso Diels-Alder reactions have been utilized as key steps in some elegant alkaloid total syntheses. Keck has prepared compound (104) (equation 40) which upon thermolysis gave an intermediate acyl nitroso species leading to adduct (105) as a mixture of epimers. This mixture was... 

Recently, Kibayashi s group (85JA5534) elegantly carried out the stereo-controlled total synthesis of gephyrotoxin (skin extracts of neopropical poison dart frog) based upon an intramolecular nitroso Diels-Alder reaction. The hydroxamic acid 365 was treated with tetrapropylammonium periodate... 

Kresze and co-workers have looked at the possibility of effecting nitroso Diels-Alder reactions enantioselectively. In a preliminary experiment, the optically active a-chloronitroso compound in Eq. (15)... 

Baldwin and co-workers have used a nitroso Diels-Alder reaction as a key step in total synthesis of tabtoxin (17), a metabolite causing leafspot disease in tobacco.41 This group has also prepared tabtoxinine /3-lactam (18), the active principle generated by in vivo enzymatic hydrolysis of 17. 

Recent advances in asymmetric nitroso Diels-Alder reactions leading, particularly, to natural products 06EJ02031. 

Total Synthesis of Nitrogen-Containing Natural Products via Nitroso Diels-Alder Reaction... 

As our first model we chose N-benzoylnortropane (12) to investigate construction of the tropane ring system based on [4 + 2] nitroso cycloaddition with a 1 3-cycloheptadiene. A search of the literature indicated that only one example of a Diels-Alder cycloaddition of a nitroso compound with a seven-membered ring diene has been reported (ref. 8). In view of this the present study of tropane synthesis was initiated by the examination of the nitroso Diels-Alder reaction of 1 3-cycloheptadiene (7) (Fig. 1). Thus reaction of 7 with the acylnitroso compound 8 generated in situ from benzohydroxamic acid by oxidation with tetrapropyl-ammonium metaperiodate (ref. 9) was carried out at room temperature, affording the [4 +2] cycloadduct 9 in 85% yield. Reduc-... 

The methodology based on nitroso DieIs-alder reaction that proved useful in the synthesis of tropane alkaloids also seemed to open an attractive route to some other alkaloids. Compared to the intramolecular imino Diels-Alder reaction (ref. Ic) the intramolecular variant of the nitroso Diels-Alder reaction has received far less attention (refs. 6b 12), despite the enormous potential it holds for alkaloid synthesis. With this in mind we proceeded to examine the application of the intramolecular nitroso Diels-Alder cycloaddition in the synthesis of alkaloids possessing saturated nitrogen heterocyclic ring systems. 

Yamamoto and co-workers developed a Class 111 process, whereby tetrazole catalyst 70 was utilized in an a-amino-hydroxylation. The resulting nitrogen anion then undergoes 1,4-addition to generate bicyclic species 197 (Scheme 1.44) [62], which although formally a [4+2] product gives the opposite regiochemistry to normal nitroso-Diels-Alder reaction (Fig. 1.10). 

Finally, Kibayashi used aqueous versions of the intramolecular acyl-nitroso Diels-Alder reaction to good effect in his stereocontrolled syntheses of (-)-swainsonine (6.28) [78] and (-)-pumiliotoxin C (6.34) [79] (Schemes 1.13 and 1.14). In each case, oxazinolactam cycloadducts (cf. 6.32 and 6.38) served as key functional chiral building blocks for the remaining synthetic operations. For example, retrosynthetic analysis of the trihydroxy-indohzidine system of swainsonine (6.28) reveals that the pyrrolidine ring of this target can be formed by amine alkylation (cf. 6.29) while the vicinal diol can be installed via substrate-controlled cw-hydroxylation of a (Z)-allyl... 

The route to ( )-porantheridine (wc-1188) adopted by Sancibrao et al. commenced with a nitroso-Diels—Alder reaction between cyclopenta-diene and the acylnitroso intermediate, made by in situ oxidation of the hydroxamic add 1219 with periodate, to produce the adduct ( )-1220... 

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 interest of the nitroso Diels-Alder reaction has been well recognized for the synthesis of natural products that contain a jyn-4-aminocyclohexanol skeleton. Yan and coworkers reported on the enantioselective synthesis of the... 

SCHEME 41.39. Intramolecular nitroso Diels-Alder reaction. 

Having completed the intramolecular nitroso-Diels-Alder reaction, the shape of the bicyclic oxazinolactam 188 allowed for a diastereoselective successive addition of two nucleophiles (Scheme 41.40). The addition of methylmag-nesium bromide into 188 at 0°C because the carbonyl is activated by the N O bond, followed by sodium boro-hydride in acetic acid, delivers the cis-2,6 disubstituted piperidine precursor 190. The diastereoselectivity could be explained by the fact that the presence of the oxazino ring would force the C4a substituent of the N-alkoxypiperidi-nium unit 189 into a pseudoequatorial position, and the stereoelectronically axial attack of the hydride led diaster-eoselectively to the desired compound 190, which was eventually transformed into (-)-lepadin B 191. 

Yamamoto Y, Yamamoto H. Catalytic, highly enantio, and diastereoselective nitroso Diels-Alder reaction. J. Am. Chem. Soc. 2004 126 4128 129. 

Yamamoto Y, Yamamoto H. Catalytic asymmetric nitroso Diels-Alder reaction with acyclic dienes. Angew. Chem. Int. Ed. 2005 44 7082-7085. 

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