Tandem reactions natural products synthesis

Tietze L. F. Domino-Reactions the Tandem-Knoevenagel-Hetero-Diels-Alder Reaction and Its Application in Natural Product Synthesis J. Heterocycl. Chem. 1990 27 47-69... 

Parsons, P.J., Penkett, C.S., Shell, A.J. (1996) Tandem Reactions in Organic Synthesis Novel Strategies for Natural Product Elaboration and the Development of New Synthetic Methodology. Chemical Reviews, 96, 195-206. 

The vast majority of the work described in this chapter was reported since 1995. Rho-dium( I)-catalyzed hydroformylation and silylformylation reactions have only very recently been adapted and developed for use in the efficient synthesis of stereochemi-cally complex natural products. In addition, the recent development of tandem reactions that take advantage of the direct production of aldehydes in these carbonylation reactions have only begun to demonstrate the versatility of this chemistry. Rhodium(I)-catalyzed hydroformylation and silylformylation, venerable reactions that have primarily been associated with organometaUic chemistry, must now be considered important tools for natural product synthesis. The continued development of these methodologies for that purpose may be expected. 

Tietze LF (1990) Domino-reactions - the tandem-Knoevenagel-hetero-Diels-Alder reaction and its application in natural product synthesis. J Heterocycl Chem 27 47-69... 

Are the above DreM tactics feasible in tandem A preliminary but affirmative answer is possible. Thus, the biaryl O-carbamate migration-amide cydization sequence 166 —> 167 —> 168 (Scheme 43), which conceptually constitutes a reaction of a biaryl 2,2 -dianion with a carbonyl dication equivalent (169), has found application in natural product synthesis [65, 72]. 

Enyne metathesis reactions in the context of natural product synthesis have been reviewed recently by Mori <2007ASC121>. Using the same ruthenium catalyst, a novel tandem diyne cycloisomerization-CM process has been devised to furnish 3,4-divinyl-2,5-dihydrofurans (Equation 57) <1999CC237>. 

Metal enolates have played a Umited role in the metal-catalyzed isomerization of al-kenes . As illustrated in a comprehensive review by Bouwman and coworkers, ruthenium complex Ru(acac)3 (51) has been used to isomerize a wide range of substituted double bonds, including aUylic alcohols (131), to the corresponding ketones (132) (equation 38) . The isomerization of aUylic alcohols affords products that have useful applications in natural product synthesis and in bulk chemical processes. An elegant review by Fogg and dos Santos shows how these complexes can be used in tandem catalysis, where an alkene is subjected to an initial isomerization followed by a hydroformylation reaction ... 

Alexis Perry conducted his undergraduate studies at the University of Glasgow, where he obtained his MSci in 2001. He joined the research group of Prof. Adam Nelson at the University of Leeds, where he developed methodology for the synthesis of C-linked azasaccharides and obtained his PhD in 2005. After a year of postdoctoral research into porphyrin-based molecular memory with Prof Maxwell Crossley (University of Sydney), he accepted a further postdoctoral position in the research group of Prof Richard Taylor at the University of York, where he is involved in the development of tandem reactions and their application in natural product synthesis. 

Tin-mediated tandem cyclization can be useful for the construction of heterocyclic rings as intermediates in natural product synthesis a series of enynes like 55 has been recently used and the reaction also represents a general route to allyl stannanes (equation 44). 

Parsons PJ, Penkett CS, Shell AJ (1996) Tandem reactions in organic synthesis novel strategies for natural product elaboration and the development of new synthetic methodology. Chem Rev 96 195-206... 

Similar processes have been designed and utilized extensively by Barriault and coworkers for efforts in natural product synthesis. An impressive example of this strategy was utilized for the synthesis of the neo-clerodane skeleton of teucrolivin A. Thermal rearrangement of 92 under microwave irradiation results in a tandem sequence featuring an oxy-Cope rearrangement, followed by the Claisen rearrangement and subsequent ene reaction to give 93. 

Hiroya K, Itoh S, Ozawa M, Kanamori Y, Sakamoto T (2002) EfiBcient construction of indole rings from 2-ethynylaniline derivatives catalyzed by coppeifll) salts and its apphcation to the tandem cyclization reactions. Tetrahedron Lett 43 1277-1280. doi 10.1016/S0040 039(01)02396-6 Hiroya K, Itoh S, Sakamoto T (2004) Development of an efficient procedure for indole ring synthesis from 2-ethynylaniline derivatives catalyzed by Cu(II) salts and its application to natural product synthesis. J Org Chem 69 1126-1136. doi 10.1021 o035528b Hiroya K, Itoh S, Sakamoto T (2005) Mild and efficient cyclization reaction of 2-ethynylaniline derivatives to indoles in aqueous medium. Tetrahedron 61 10958-10964. doi 10.1016/j.tet. 2005.08.098... 

Treatment of ketone (69) with excess amounts of t-BuMe2SiOTf and bis[(k)-l-phenylethyl]amine ((i )-BPEA) gives tricyclic silyl aldolate (70) with moderate enantioselectivity [104]. The formation of (70) can be explained by the enol silylation to (71) followed by a tandem Michael-aldol reaction. The asymmetric induction by the chiral amine occurs in the enol silylation (Scheme 9.40). The combined use of silyl triflates and amines has been applied to an intramolecular aldol reaction for natural product synthesis [105]. 

Since its original report, the StiU-Gennari modified HWE olefination has been widely used in natural product synthesis to access Z-alkenes [18]. One example from the Roush group is shown in Fig. 5, where the olefinatimi reaction was used to provide the conjugated polyene precursor for their key one-pot tandem intramolecular Diels-Alder reaction and vinylogous Baylis-Hilhnan cycUzation [19]. 

In the previous section we have shown that tandem ene-yne-ene RCM has been broadly used for the rapid and efficient construction of complex frameworks. In principle, selective alkene metathesis can be combined with other types of transformation to achieve a cascade reaction, which will provide a tremendous increase in molecular complexity [77]. Therefore, in this section, we highlight several recent examples of cascade reaction involving selective alkene metathesis for natural product synthesis. 

One of the most successful embodiments of this concept combined a metathetical step with the selective isomerisation of a terminal C=C double bond, and found applications in natural product synthesis. As discussed in Sections 7.3.2.2 and 7.3.2.3, it is indeed possible to convert the metathetically active benzylidene initiator 20 into hydrido complex 43, simply by adding trimethyl(vinyloxy)silane or methanol to the reaction mixture, thereby triggering a consecutive catalytic isomerisation process. Other methods for the decomposition of ruthenium metathesis catalysts for use in tandem with olefin isomerisation reactions include treatment with hydrogen, formic acid, sodium borohydride, or sodium hydroxide in isopropanol. ... 

The synthesis of (-l-)-arteanniun M by Barriault and Deon provides an excellent demonstration of memory of chirality in natural product synthesis.Synthesized from enantio- enriched limonene (98% ee), the 1,2-divinyl cyclo-hexenol 186 underwent tandem oxy-Cope/transannular ene reaction to give 187 (Scheme 20.45). The reaction was highly diastereoselective as only one diastereomeric... 

Dell C. P. Cycloaddition in Synthesis Contemporary Organic Synthesis 1997 4 87 Keywords natural products, metal catalyzed, asymmetric reactions, Ionic reactions, transannular reactions, tethered reactions, tandem reactions, benzo-qulnones, quinodimethanes, hefero-Dlels-Alder reactions... 

In a series of publications over the past few years, the group of Barriault has reported on microwave-assisted tandem oxy-Cope/Claisen/ene and closely related reactions [175-178], These pericyclic transformations typically proceed in a highly stereoselective fashion and can be exploited for the synthesis of complex natural products possessing decalin skeletons, such as the abietane diterpene wiedamannic... 

A systematic exploration of the intramolecular [4+2]/[3+2] cycloaddition cascade of 1,3,4-oxadiazoles was described. The studies permit the use of unsymmetrical dienophiles, dipolarophiles, and oxadiazoles as well as to control the cycloaddition regioselectivity and diastereoselectivity. The scope and utility of the reaction were defined <2006JA10589>. The tandem intramolecular [4+2]/[3+2] cycloaddition cascade reaction of 1,3,4-oxadiazole was applied to the syntheses of a series of natural products including a total synthesis of (-)- and ent-(+)-vindoline <2006JA10596>. 

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