Annulation stereoselective

Lee, H.B., Sung, M.J., Blackstock, S.C., and Cha, J.K. (2001) Radical cation-mediated annulation. stereoselective construction of bicyclo[5.3.0]decan-3-ones by aerobic oxidation of cyclopro-pylamines. Journal of the American Chemical Society, 123, 11322-11324. 

The resulting alkyllithium produced after cyclization has also been successfully trapped with several electrophiles in fair to excellent yield. This annulation stereoselectively gives the syn isomer in 10 1 to >50 1 hut is hmited to five-membered ring formation and has not heen applied to highly functionalized carhocycles. 

Ring closure of functionalized dienones occurs again in 1,4-fashion to give an annulated six-membered ring. Both Lewis acid (ethylaluminum dichloride) and fluoride ion can be employed, but the chemical yield of this particular cyclization is low and no stereoselection regarding the position of the vinyl side chain was achieved35. 

Stereoselective Ring Annulations by Intramolecular 1,6-Addition of an Allylsilane Function... 

Table 2. Stereoselective Annulation with 1,3-Asymmetric Induction Using Ethylaluminum Dichloride as Lewis Acid...

Stereoselective d.v-annulations of cyclopcntenones arc, however, possible using these procedures employing 1,3- or 1,4-bisMichael donors. 

Loh and coworkers used a combination of a carbonyl-ene and an oxenium-ene reaction for the synthesis of annulated tetrahydropyrans 1-61, using methylenecyclo-hexane 1-60 as substrates (Scheme 1.16) [15]. The most appropriate catalyst for this reaction with the aldehydes 1-59 turned out to be In(OTf)3, which furnished the desired products in good to excellent yields and high stereoselectivity [16]. 

The novel [6+2] annulation approach developed by the Takeda group has also been included in a threefold anionic/pericyclic process (Scheme 2.149) [340]. The reaction leads to functionalized eight-membered rings 2-659 in a highly stereoselective manner, starting from acylsilanes 2-656 and 3-(trimethylsilyl)vinyl-lithium (2-657). After 1,2-addition and 1,2-Brook rearrangement, the cyclobutane 2-... 

Substituted (5R,6A,)-6-(dimethyl(phenyl)silyl)-2-phenyldihydropyrazolo[l,2- ][l,2,4]triazole-l,3(2//,5//)-dione 716, synthesized via the [3+2] annulation of a-substituted allylic silanes 715 with PTAD, were oxidized to the corresponding hydroxy substituted urazoles 717. This work shows that allylsilanes with a single substituent at the allylic carbon undergo exclusive stereoselective [3+2] annulation (Scheme 114) <2007TL6671>. 

Watt and Drummond, were considered to be inert for C-C bond forming reactions. However, by the expedient of transmetallation to Cu, Ni, Zn, Li, and Al, methodologies for the stereoselective synthesis of olefins and dienes, as well as unusual heterocycles, aromatics and their ring-annulated products are now available which are beginning to make impact on material science, e. g. synthesis of pentacenes and polyphenylenes. Takahashi and Li provide evidence that, with further developments in transmetallation and handling the zirconacycles outside of the Schlenk tube techniques, synthetic utility will increase and new catalytic reactions will be developed. 

The azatriquinane 36a which may be regarded as an annulated bis-pyrrolizine readily undergoes stereoselective hydrogenation in presence of rhodium on alumina, leading to the fully saturated tricyclic compound with a trans relative orientation between the benzyl group and the two hydrogen atoms located on the two other junctions carbon atoms <2005JA1352>. 

Unlike with sodium borohydride (see Section 11.01.5.2), pyrrolizin-3-one 2 reacts with lithium aluminohydride mainly as an amide. No conjugate addition occurs, and only the reductive lactam cleavage takes place to give stereoselectively the (Z)-allylie alcohol 77. Similarly, benzo-annulated pyrrolizin-3-one 17 gives the corresponding benzylic alcohol 78. The same reactivity was observed with organometallics such as methyllithium which gives exclusively the tertiary (Z)-allylic alcohol 79 (Scheme 7). 

Wender et al. s [5 + 2] metal-catalyzed annulation strategy has also been applied to the total synthesis of (+)-aphanamol I (154) [34]. The scope of this method was expanded by using a tetrasubstituted allene that resulted in the stereoselective formation of an angular methyl group. The reaction of allene 149 with 0.5 mol% of rhodium biscarbonyl choride dimer afforded the fused bicyclic product 152 in 93% yield with complete exo/endo and diastereoselectivity (Scheme 19.28). The stereoselectivity of this process was attributed to a preference for formation of the cis-fused metallo-... 

While this example of the Robinson annulation is clearly not enantioselec-tive, the same antibody converts the mero-ketone [120] into the Wieland-Miescher (WM) decalenedione product kcM = 0.086 min-1 and Km = 2.34 mM at 25°C, parameters that give an impressive ER of 3.6 x 106. Good evidence suggests that the mechanism of the reaction involves the formation of a ketimine with the e-amino group of a buried lysine residue in the antibody, as shown in Fig. 39. Most significantly, the reaction delivers the ( )-(+)-WM product in 96% ee (by polarimetry) and in 95% ee by nmr and hplc analysis for a 100 mg scale reaction. A recent report tells that this antibody is to be made commercially available at a cost of 100 for 10 mg. The realization of that objective would mark the start of a new era of application of abzymes to organic stereoselective synthesis. 

Strategies based on two consecutive specific reactions or the so-called "tandem methodologies" very useful for the synthesis of polycyclic compounds. Classical examples of such a strategy are the "Robinson annulation" which involves the "tandem Michael/aldol condensation" [32] and the "tandem cyclobutene electrocyclic opening/Diels-Alder addition" [33] so useful in the synthesis of steroids. To cite a few new methodologies developed more recently we may refer to the stereoselective "tandem Mannich/Michael reaction" for the synthesis of piperidine alkaloids [34], the "tandem cycloaddition/radical cyclisation" [35] which allows a quick assembly of a variety of ring systems in a completely intramolecular manner or the "tandem anionic cyclisation approach" of polycarbocyclic compounds [36]. 

The reaction of (trialkylsilyl)vinylketenes with nucleophilic carbenoid reagents, such as sulfur ylides and diazo compounds, has been used for synthesis of substituted cyclopentenones by stereoselective 4 + 1-annulation (Scheme 12). The strategy relies on the remarkable ability of silyl substituents to stabilize ketenes and suppress their tendency to undergo dimerization and 2 - - 2-cycloaddition. 

The class of 3-silyl-substituted reagents provides, upon addition with aldehydes, allylic silanes that offer many options for further derivatization. Oxidative processes are described in previous sections (see the sections on Preparation of 1,2-Diols and 1,4-Diols). If the appropriate silicon substituents are chosen, formal [3+2] cycloadditions with aldehydes can be promoted under Lewis acid catalysis. For example, the mismatched addition of the Z-3-propyl-3-benzhydryldimethyl allylsilane 183 to an a-benzyloxy aldehyde proceeds with low diastereofacial selectivity in favor of product 184 however, after protection of the secondary alcohol, an efficient [3+2] annulation provides the polysubsubstituted furan 185 in good yield and acceptable stereoselectivity (Scheme 24). ° The latter is brought forward to a tricyclic unit found in the antitumor natural product angelmicin B. 

To carry out tethered [3-i-2]-cycloadditions Nakamura et al. developed the new annulating reagents 123 [109, 110]. The reagents carry, in one molecule, two cyclopropenone acetals that are connected with an n-carbon methylene tether. Upon thermolysis in the presence of Cjq, the reagent undergoes [3-i-2]-cycloaddition reaction twice in a regio- and stereoselective manner to give Q- and C2-symmetrical bisadducts with cis-l - and cis-3-addition patterns, respectively. The selectivity varies... 

The diacetate of 711 has also been produced in stereoselective fashion via a route beginning with dicyclopentadiene (Scheme LXXVI) Ketone 712 was transformed into dimethylated alcohol 713 whose ozonolysis provided 714. Following Jones oxidation, decarboxylation with concomitant introduction of a double bond was realized by application of Kochi s prowdure. A lengthy quence of steps to adjust functionality led up to annulation by a modified Wichterle sequence. The conversion of 715 to 716 was accomplish by standard reactions. 

The procedure described here serves to illustrate a general [3+2] annulation method for the synthesis of cyclopentane derivatives. A unique feature of this one-step annulation is its capacity to generate regio-specifically five-raembered rings substituted at each position, functionally equipped for further synthetic elaboration. As formulated in the following equation, the reaction proceeds with remarkably high stereoselectivity via the effective suprafacial addition of the three-carbon allene component to an electron-deficient olefin ("allenophile"). ... 

Some representative examples of the [3+2] annulatlon are listed in Table 1. Both cyclic and acyclic allenophiles participate in the reaction, a-Alkylidene ketones undergo annulation to provide access to spiro-fused systems, and acetylenic allenophiles react to form cyclopentadiene derivatives. The reactions of (E)- and (Z)-3-methy1-3-penten-2-one illustrate the stereochemical course of the annulation, which proceeds with a strong preference for the suprafacial addition of the allene to the two-carbon allenophile. The high stereoselectivity displayed by the reaction permits the stereocontrol led synthesis of a variety of mono- and polycyclic systems. 

A. A. Ghini, C. Bumouf, J. C. Lopez, A. Olesker, and G. Lukacs, Intramolecular Diels-Alder reactions on pyranose trienes. Stereoselective access to bis-annulated pyranosides. Tetrahedron Lett. 37 2301 (1990). 

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