Acylnitroso Diels-Alder

A type 2 intramolecular /V-acylnitroso Diels-Alder reaction of hydroxamic acid 177 followed by catalytic hydrogenation of the double bond was employed for the synthesis of substituted bridged bicyclic derivative 178, as a single diastereomer (Scheme 75 <2002OL2637>). Cleavage of the N-O bond was performed by reduction with Na(Hg) amalgam and provided m-3,7-disubstituted azocane 9, as a single isomer in 80% yield. 

Diastereoselective acylnitroso Diels-Alder reactions were performed using enantiopure hydroxamic acids derived from camphor and a-amino acids as chiral auxiliaries (Equation 90) <1997JOC3806, 1998T10537, 2003TL4571>. 

W. Lee, K.-H. Kim, M. D. Surman, and M. J. Miller, Stereo- and regioselectivity of Pd/In mediated allylic additions to aldehydes and ketones. In situ generation of allylindium(III) intermediates from /V-acylnitroso Diels-Alder cycloadducts, and 1 -amino-4-acetoxycyclopentanes, J. Org Chem., 68 (2003) 139-149. 

During the past few years, acylnitroso Diels-Alder cycloadditions have been used as the key step in several natural product total syntheses. Retey et al.40 have used the adduct from cyclopentadiene and the acylnitroso compound derived from 3,5-dinitrobenzoic acid35 to synthesize the antitumor compound neplanocin A (16) (Scheme 3-XI). 

The hetero Diels-Alder reaction <01H1591, 01TL5693> and dipolar cycloadditions continue to constitute important approaches to piperidines. Kibayashi and co-workers used an intramolecular acylnitroso Diels-Alder reaction to synthesize (-)-lepadins A,B, and C from an acyclic precursor <01JOC3338>. An intramolecular nitrone cycloaddition was used by Machetti and co-workers to produce both enantiomers of 4-oxopipecolic acid <01T4995>. Their synthesis proceeds from a nitrone bearing an a-methylbenzylamine chiral auxiliary. Noteworthy in this report is the presence of large-scale experimental procedures the nitrone formation and cycloaddition reactions were performed on 285 mmol and 226 mmol scales, respectively. 

The hetero-Diels-Alder reaction of steroidal dienes (156) with nitroso-aromatics are regioselective with two stereoisomers (157) and (158) produced in a 2 1 ratio (Scheme 60) The regio-, stereo-, and enantio-selectivity of 4 -I- 2-cycloadditions of nitrosoalkenes to alkenes have been extensively reviewed.The intramolecular acylnitroso Diels-Alder cycloaddition of (159) produced the bicyclic adducts (160) in high yields (Scheme 61). ... 

Naruse, M. Aoyagi, S. Kibayashi, C., Total synthesis of (-)-pumiliotoxin C by aqueous intramolecular acylnitroso Diels-Alder approach. Tetrahedron Lett., 1994,35,9213-16. 

Pericycttc Reactions Although a wide variety of ring-expansion processes through pericyclic cyclizations have been described, only a few cycloaddition methods were depicted for the direct generation of medium-ring heterocycles. The most attractive approaches were the [4-1-3] cycloaddition, the 1,3-dipolar cycloaddition of nitrone, and the type-2 intramolecular N-acylnitroso Diels-Alder reaction. 

Cycloadditions The intramolecular A -acylnitroso Diels-Alder (D-A) reaction of a substrate, in which the dienophile is attached to the position 2 of the diene (type 2 D-A reaction), provided an interesting solution to the highly regioselective synthesis of bridged bicyclic oxazinolactams containing a bridgehead... 

Scheme 4.22 Synthesis of the tricychc BCD core of stenine by intramolecular Af-acylnitroso Diels-Alder reaction.

Sparks, S. M., Chow, C. P., Zhu, L., Shea, K. J. (2004). Type 2 intramoleculariV-acylnitroso Diels-Alder reaction scope and application to the synthesis of medium ring lactams. Journal of Organic Chemistry, 69, 3025-3035. 

The Keck group described an approach to the pyrrolizidine alkaloids that revolved around acylnitroso Diels-Alder chemistry. The plan, outlined within the context of an approach to heliotridine (38), was to once again use an intramolecular N-alkylation to construct the N4-C3 bond. N-Alkylation substrate 39 was to be prepared by reduction of the N-O bond of 40, which was to result from an intramolecular cycloaddition of 41. It was hoped that the C7 substituent might induce relative stereochemistry at 07 by occupying a site on the convex face of the incipient azaoxabicyclo[4.3.0]nonane ring system in the cycloaddition transition state. Note that the cycloaddition of 41 establishes the olefin geometry needed to support the intramolecular N-alkylation. 

Kibayashi, C. Aoyagi, S. Nitrogenous Natural Products via N-Acylnitroso Diels-Alder Methodology Synlett 1995, 873-879. Corrie, J. E. T. Kirby, G. W. Sharma, R. P. Formation of Aryl Isocyanates by Deoxygenation of Nitroso-carbonylarenes J. Chem. Soc., Chem. Commun. 1975, 915-916. Kirby G. W. Sweeny, J. G. Nitrosocarbonyl Compounds as Intermediates in the Oxidative Cleavage of Hydroxamic Acids /. Chem. Soc., Chem. Commun. 1973, 704-705. 

Ozawa T, Aoyagi S, Kibayashi C. Total synthesis of the marine alkaloids (—)-lepadins A, B, and C based on stereo-controlled intramolecular acylnitroso-Diels-Alder reaction. J. Org. Chem. 2001 66(10) 3338-3347. 

Abe, H., Aoyagi, S., and Kibayashi, C. (2000) First total synthesis of the marine alkaloids ( )-fascicularin and ( )-lepadiformine based on stereocontrolled intramolecular acylnitroso-Diels-Alder reaction. J. Am. Chem. Soc., 122, 4583-4-592. 

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