Intramolecular Diels-Alder approach

Keywords enantiospecific synthesis, intramolecular Diels-Alder approaches... 

In our efforts toward strychnine, we have integrated an intramolecular Diels-Alder approach to its tetracyclic core with an organometallic D-ring closure. Both of these key reactions were certainly inspired by the previous accomplishments of others as described above. 

The same author used this strategy to synthesize tricydic taxoid skeletons 55, an intramolecular Diels-Alder approach that proceeds in the direction from left to right (ring A to BC) (Scheme 9.14) [56], Once again, microwave irradiation was necessary to perform the required cycloaddition in good yield. 

Lu, Y.-F. and Fallis, A.G., An intramolecular Diels-Alder approach to tricyclic taxoid skeletons, Tetrahedron... 

TOTAL SYNTHESIS OF BIOLOGICALLY INTRIGUING DRIMANE-TYPE SESQUITERPENOIDS VIA INTRAMOLECULAR DIELS-ALDER APPROACHES... 

Scheme 5. Intramolecular Diels-Alder approaches to the decalin core...

Trace amounts of complexes 3 and 20 promote the synthesis of optically pure, multiply functionalized, versatile intermediates such as pyrones or lactones from activated, acid-labile siloxydienes with aldehydes. The reagents typically work under mild conditions and therefore promote the survival of valuable functionality in the dienophile, the diene, and cycloadduct [105-107]. As a consequence this procedure is applied in the total synthesis of various natural products, often requiring an intramolecular Diels-Alder approach [106]. Specific interactivity of the chiral precatalyst Eu(hfc)3 (hfc = 3-(heptafluorpropylhydroxymethylene)-D-camphorate with Danishefsky s diene bearing a chiral auxiliary resulted in cycloaddition products of high diastereofacial excess (95 % eq. (8)) [105]. 

Total Synthesis of Biologically Intriguing Drimane-Type Sesquiterpenoids Via Intramolecular Diels-Alder Approaches... 

Scheme 7-45 An intramolecular Diels-Alder approach to the esperamicin enediyne core (Schreiber and co-workers).

Schreiber et al. have been able to apply their enediyne intramolecular Diels-Alder approach to the synthesis of dynemicin model systems [268-270], culminating in the total synthesis of di- and tri-O-methyl dynemicin A methyl esters 388 and 389 (Scheme 7-78) [271], derivatives of the natural product itself. Highlights of this synthetic approach include (a) intramolecular lactonization and concomitant Diels-Alder cyclization (380- 381) (b) allylic hydroxylation followed by an allylic diazene rearrangement in order to regiospecifically isomerize a double bond (381 - 382) (c) a-hydroxylation of the lactone 381 and subsequent conversion to the P-ketoester 383 (d) annelation of the anthraquinone unit (383- 384- 385- 386) (e) mild base-induced P-elimination of the N-protecting group of 386 to give the free amine 387 and (f) a final oxidation to complete the anthraquinone (387 - 388). 

A Sulfolene-based Intramolecular Diels-Alder Approach to the Synthesis of Manzamine A. Leonard, J. Fearnley, S. P. Finlay, M. R. Knight, J. A. and Wong, G. J. Chem. Soc., Perkin Trans. 71994, 2359. 

Tadano K-i (2009) Natural product synthesis featuring intramolecular Diels-Alder approaches - Total Syntheses of tubelactomicins and spiculoic acid A. Eur J Oig Chem 4381 394... 

Finally, a conceptually similar reaction involves the addition of (1) to an acyl imminiiim salt to give an intermediate (38) (eq 18) which was then used in an intramolecular Diels-Alder approach to the heteroyohimboid alkaloids. A Michael adduct is formed when (1) is allowed to react with 2,2-bis(phenylsulfonyl)styrene, probably as the result of a Diels-Alder reaction in which the adduct reverses to a zwitterion and internally deprotonates. Also the lithium enolate derived from (1) has been added in a Michael fashion to o , -unsaturated ketones to give, after silylation, the same adducts as the direct Diels-Alder reaction but at much lower temperatures. ... 

VoYLE, M., K. S. Kyler, S. Arseniyadis, N. D. Dunlap, and D. S. Watt Quassinoids. 1. Attempted Intramolecular Diels-Alder Approach for Assembling the ABCD Rings. J. Org. Chem. 48, 470 (1983). 

A stereoselective total synthesis of ( )-A -capnellene via the intramolecular Diels-Alder approach. /. Chem. Soc. Chem. Commun., 646-647. 

Grimmins, M.T, Brown, B.H., and Plake, H.R. (2006) An intramolecular Diels-Alder approach to the eimicellins enantioselective total synthesis of ophirin B and astrogorgin. /. Am. Chem. Soc., 128,1371-1378. 

---