Nitronate structures stereoselectivity

Structures 81 (R - Me, Bn) were made from a 3 -ketonucleoside by formation of the nitrone and stereoselective reduction. The esr spectra of some of the free radicals spontaneously formed from the hydroxylatnines were also studied. ... 

Cycloadditions of nitrones, nitrile oxides or diazo compounds to thiete dioxides do not show the high stereoselectivity observed with acyclic vinyl sulfones, and mixtures of the two possible adducts are formed . The charge-transfer stabilization energy calculated according to the Klopman-Salem perturbational approach is able to account for the experimental trends of the isomer ratio in terms of the major stereochemical structural differences between the acyclic vinyl sulfones and the four-membered ring sulfones (see Section IV.B.3). 

High stereoselective addition of vinylmagnesium bromide to L-tartaric acid-derived nitrone was used as a key step in the synthesis of (+ )-lentiginosine and its structural analogs (653). 

The wide variety of methods for the preparation of alkyl nitronates, gives rise to a broader diversity of structures compared to silyl nitronates. Alkyl nitronates can be grouped into two subclasses, acyclic and cyclic. Both subclasses participate in dipolar cycloadditions with similar reactivity, however, minor differences are manifest in their stability and stereoselectivity. Additionally, the ability to prepare cyclic nitronates allows access to a wide variety of novel, multicyclic ring stractures. 

Intramolecular cycloaddition of fV-benzyl-substituted 3-O-allylhexose nitrones furnishes chiral oxepane derivatives. The regioselectivity of the cycloaddition depends on several factors such as (1) the structural nature of the nitrone, (2) substitution and stereochemistry at 3-C of the carbohydrate backbone, and (3) substitution at the terminus of the O-allyl moiety. A mixture of an oxepane and a pyran is formed in the intramolecular oxime olefin cycloaddition of a 3-O-allyl carbohydrate-derived oxime <2003T4623>. The highly stereoselective synthesis of oxepanes proceeds by intramolecular nitrone cycloaddition reactions on sugar-derived methallyl ethers <2003TA3899>. 

Yield, regioselectivity and stereoselectivity depend on the structure of the nitrone. 

Yield, regioselectivity and stereoselectivity depend on the structure of the nitrone.74-76-77 For example, although 3,3,3-trifluoro-l-(phenylsulfonyl)propene provides high yields of cyclo-... 

Tandem pericyclic reactions are a powerful strategy for construction of complex, polycyclic compounds. In recent years tandem [4 + 2]/[3 + 2] chemistry of nitro-alkenes and nitronates has been developed by Denmark et al. as a general approach to functionalized pyrrolidine-containing structures [118]. Within the subclass of inter [4 -I- 2]/intra [3 + 2] cycloadditions, they have documented the fused mode (/3-tether, Eq. 77), spiro mode (a-tether, Eq. 78), and bridged mode (a-tether, Eq. 79 or /3-tether, Eq. 80) constructions. These are highly stereoselective processes in the presence of Lewis acid such as SnCU and are amenable to asymmetric modification by use of chiral vinyl ethers. Finally, the nitroso acetals are readily transformed, by hydroge-nolysis, into polycyclic, a-hydroxypyrrolidinones, 4-aminocyclohexanones, and cyclo-pentylamines. 

Werner, K. M., De los Santos, J. M., Weinreb, S. M., Shang, M. A Convergent Stereoselective Synthesis of the Putative Structure of the Marine Alkaloid Lepadiformine via an Intramolecular Nitrone/1,3-Diene Dipolar Cycloaddition. J. Org. Chem. 1999, 64, 686-687. 

Intramolecular cycloadditions via nitrones as intermediates are generally highly stereoselective processes that are used to generate a number of stereocenters in a complex molecule3-5-6-8- 8. The intrinsic rigidity of the transition structures enhances the stereocontrol exerted by steric and stereoelectronic factors (see Section A.2.3.5.). Tor more recent examples of intramolecular cycloadditions via nitrones, see references 337-354. 

These intramolecular C-4-alkenyl nitrone cycloaddition reactions afford m-fused products with complete endo stereoselection. The induced stereoselection is also high and may be rationalized by the assumption that the transition structures with the bulkier substituent(s) at the stereocentcr(s) in a pseudo-equatorial position are favored over those with these groups in the pseudo-axial position. In conformationally mobile acyclic systems this generally results in a trans arrangement between the preexisting stereocenter and the newly formed stereocenter. This tendency seems compelling for x-substituted nitrones. In cyclic systems steric factors dictate the stereochemical outcome of the reaction. 

The cycloaddition of nitrones lOj or 10k with various cyclic olefins is also stereoselective, and the ratio of exo (Vc)- and endo (Vt)-adducts depends on the structure of olefins, and to some extent on the nature of the ring-substituent, althouth generalization is difficult.69 The reaction of nitrone 10j with dimethyl tricyclo[4.2.2.02, ]deca-3,7,9-triene-7,8-di-carboxylate is also stereoselective. The endo-(12c)/e.vo(12d) adduct ratio is 0.5.53 The cycloaddition of nitrone lOj with some complex aji-unsaturated ketones is reported.70 The reaction with lumisantonin is regioselective to give a mixture of Vic (24%) and Vc (8%)71 (the carbonyl side chain is taken as X). The reaction with dihydrofuran is regio- and stereospecific. 6... 

Schreiber s early efforts in this area were focused on libraries of compounds having structural features reminiscent of rigid, complex, stereochemically rich natural products. In a key early example, solid-phase split-pool synthesis was used to generate a combinatorial library of over two million complex, polycyclic compounds derived from shikimic acid [17]. A stereoselective tandem acylation-nitrone cycloaddition was used to generate 18 tetracyclic scaffolds, to which 30 alkynes were coupled using a Sonogashira reaction, 62 amines were coupled via y -lactone aminolysis, and 62 carboxylic acids were coupled by alcohol esterification (Fig. 9.1-3(c)). In addition, a portion of the solid supports were left unreacted at each of the last three steps to generate a skip codon that further increased the diversity of the library. 

It should be mentioned that the stereoselectivity of cycloaddition of chiral sugar-derived nitrone to an alkene is difficult to predict, and would appear to be dependent on minor structural changes in either component. Three structural features can influence the stereochemical outcome of nitrone/alkene cycloadditions /Z nitrone isomerization about the C = Nbond, alkene or/and nitrone facial selectivity, and endolexo preferences [6j. 

Stereoselectivity of l S-Dipolar Cydoaddition. The stereoselectivity of the intermolecular cycloaddition of an acyclic nitrone to an alkene is difficult to predict, and wotdd appear to be susceptible to minor structural changes in either component (13). The chiral 2,2-dimethyl-l,3-dioxolan-4-yl nitrone showed only modest astereoface selectivity in its addition to methyl crotonate (14). However, the more hindered tetramethyl-l,3-dioxolan-4-yl nitrone was more selective. 

Thus the cycloaddition of the C-glycosylnitrones to V-arylmaleimides would appear to proceed with useful stereoselectivity, but the nature of the stereoselectivity is dependent upon the precise functionality present in the nitrone. We have demonstrated that small structural change in the nitrone result in significant changes in the steroselectivity of cycloaddition. 

On the basis of ESl-MS observation as well as positive nmilinear effects of this system, we assumed that p-oxo-p-aiyloxy-trimer complex is the most enantiose-lective active species (Fig. 3). Therefore, Sm50(0-/Pr)i3 with a well-ordered structure would have beneficial effects for the formation of desired trimer species. Postulated catalytic cycle of the reaction based on the initial rate kinetic studies and kinetic isotope effect studies is shown in Fig. 4. In this catalyst system, both Cu and Sm are essential. We assume that the cooperative dual activation of nitroalkanes and imines with Cu and Sm is important to realize the syn-selective catalytic asymmetric nitro-Mannich-type reaction. The Sm-aryloxide moiety in the catalyst would act as a Brpnsted base to generate Sm-nitronate. On the other hand, Cu(ll) would act as a Lewis acid to control the position of iV-Boc-imine. Among possible transition states, the sterically less hindered TS-1 would be more favorable. Thus, the stereoselective C-C bond formation via TS-1 followed by protonation with phenolic proton affords syn product and regenerates the catalyst. 

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