Tandem stereospecific

Thomas, N.F. Lee, K.C. Weber, J.-F.F. Wahab, LA. Awang, K. Hadi, A.H.A. Richomme, P., Tandem Stereospecific Radical Cation-Mediated Syntheses of Oligostilbenoid Dimers. In Frontiers in Natural Product Chemistry, Atta-ur-Rahman/Choudhary/Khan, Ed. Bentham Science Publishers Ltd. 2005 Vol. 1, pp 19-30. 

Aluminum oxide catalyzed addition of ethyl nitroacetate to racemic 2,3-cpoxy aldehydes 7 affords substituted 4,5-dihydroisoxazole 2-oxides through a regio- and stereospecific tandem nitroaldol cyclization process. High diastereoselectivities are observed in the reaction of cis-epoxyaldehydes to yield the ethyl, vi7 -4.5-dihydro-4-hydroxy-5-( I -hydroxyalkyl)-3-isoxazole-carboxylate 2-oxides, with tram configuration at the ring positions, whereas reactions of trans-and 3,3-disubstituted 2,3-epoxyaldehydes proceed with lower selectivities28. 

This tandem intramolecular silylformylation/Sakurai reaction has successfully been applied in a formal total synthesis of mycoticin A [75]. The scope and utility of these reactions was expanded to (Z)- and (E)-crotyl groups leading to the stereospecific incorporation of both anti and syn propionate units into the growing polyol chain (Scheme 21) [76]. 

McDonald and coworkers studied a series of tandem endo-selective and stereospecific oxacyclization of polyepoxides by reaction with Lewis acid [92-95]. Polyepoxides, such as 50, can be obtained from the epoxidation of triene 49 with ketone 26 (Scheme 8). This cascade cyclization of polyepoxides provides an efficient method to synthesize substituted polycyclic ether structures, which are present in a number of biologically active marine natural products. 

The reactions of 1,2,3-triazolium 1-imide (277) with a range of alkene and alkyne dipolarophiles give rise to a variety of new ring systems (Scheme 54). Compounds (276) and (278) are obtained from (277) by reaction with acrylonitrile and DMAD, respectively. These reactions are tandem 1,3-dipolar (endo) cycloadditions and sigmatropic rearrangements which are regio- and stereospecific <90JCS(Pl)2537>. Kinetic and mechanistic studies show that these reactions are dipole-HOMO controlled. The second-order rate constants are insensitive to solvent polarity, the reaction indicates... 

Regio- and diastereoselective rhodium-catalyzed tandem allylic alkylation of 71 with stabilized carbon and heteroatom nucleophiles 72 followed by the PK annulation by the same catalyst was described by Evans and co-workers. Alkylation of an optically active allylic alcohol carbonate 71 proceeds in a regio- and stereospecific manner successfully at 30 °C by 7r-acidic Rh(i) catalysts (Equation (41)). The resultant product then undergoes the PKR with the aid of the pre-existing catalyst under GO pressure at elevated temperature. ... 

Carbocyclization of m-alkcnyl-z-methoxybcnzy I lithiums to form five- or six-membered rings has been studied 101 the five-membered ring is formed with a cis-stereochemical relationship between the methoxy substituent and the adjacent methyl group. Intramolecular carbolithiation of vinyl sulfides at — 105°C in THF has been found to occur non-stereospecifically with regard to the newly formed C—Li centre.102. The stereochemistry of selective tandem Michael addition alkylation reactions of vinylphosphonates has been explored.103... 

A review of intramolecular 4 + 3-cycloadditions of allyl cations has been presented.277 The 4 + 3-cycloaddition reaction of C(2)-substituted furans with 1,3-dimethyloxyallyl cations show high endo diastereoselectivity and a cis dia-stereospecificity.278 The tandem Peterson olefination/[4 + 3]-cycloaddition of tertiary alcohols (149) in the presence of filran and Lewis acids (TiCLt) furnishes cycloheptanes (150) in modest yields (Scheme 57).279 (Trimethylsilyl)methyl allylic sulfones (151) were used to investigate the scope and limitations of intramolecular 4 + 3-cycloadditions of allylic sulfones (Scheme 58).280 Lewis acid-catalysed 4 + 3-... 

Nature found a direct path to perform this tandem fragmentation cyclization reaction in a stereospecific manner and under neutral conditions. Human creativity and luck aimed to uncover synthetic variants, which can compete efficiently with it. With the advent of mild, metal mediated cyclization reactions, the early idea of Grosheinz and Fisher [19a], who converted 6-deoxy-6-nitrohexoses to nitroinositols in a single step, matured to a general strategy of broad interest. 

A tandem aldol condensation-radical cyclization sequence has been developed for the preparation of functionalized bicyclo[3.3.0]octane systems [116]. Conjugate addition of Me2AlSePh to dimethylcyclopentanone (118) followed by trapping of the resulting enolate with aldehyde gave predominantly the trans, erythro aldol 119 this then underwent radical cyclization with BusSnH and catalytic AIBN yielding the bicyclic ketol 120 stereospecifically (Sch. 80). 

A semipinacol rearrangement in tandem with a cyclization has been shown to be a powerful method for the construction of carbocyclic rings. Here the cyclization is initiated by an acetal function and terminated by a semipinacol rearrangement (Scheme 25). In some cases, the cyclization has been found to be stereospecific at the acetal center (equation 48), and up to four chiral centers can be generated in a single step (equation 49). Highly substituted tetrahydrofurans are obtained from cyclic acetals (Scheme 26), and stereoselective tetrahydrofuran annelations are possible using bicyclic acetals (Scheme 27). ... 

Also, dianions derived from y-substituted /f-ketoesters engage in condensations with oxiranes, to afford 2-carbomethoxyethylidene-tetrahydrofurans in a stereospecific manner <92SL529>. In certain cases these types of reactions can be effected on an alumina surface without solvent. In a base-catalyzed tandem nitroaldol cyclization process <90JOC78l>, 2-isoxazoline-2-oxides are formed in... 

Mechanistic studies have discounted the possibility that cycloadduct 70 arises from a tandem Michael-aldolization pathway [ 140]. Stereospecificity is observed using fumaronitrile trans double bond) or maleonitrile cis double bond) as di-enophiles, indicating either a concerted reaction or a rapid second step (aldol) relative to internal bond rotation. Upon treatment with triethylamine in methanol, ring opening to the formal Michael adduct, a thermodynamic sink, is observed this Michael adduct was not formed in the enantioselective catalytic reaction. Further, the Michael adduct was not converted to cycloadduct 70 upon treatment with quinidine in chloroform in fact, access to 70 from the Michael product could be achieved only under fairly special conditions. 

Figure 10 (a) Epoxidation reactions on des-epoxy cryptophycin anaiogues cataiyzed by CrpE, Recombinant CrpE cataiyzes regio- and stereospecific instaiiation of the /3-epoxide toward cyciic substrates to generate both naturai and unnaturai cryptophycin anaiogues. No seco-substrate is utiiized by CrpE, (b) In vitro tandem reactions toward seco-cryptophycin 4 cataiyzed by enzymes TE and CrpE to yieid cryptophycin 2 (23),... 

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