Stereocontrolled synthesis

The synthesis of the tricyclic intermediate A was further improved by the development of a short and stereocontrolled synthesis of compound B (Ref. 9) ... 

This reaction has received especial attention for the stereocontrolled synthesis of polyfluorinated artrfieial pyrethroids [65, 66] (equation 52). 

Stereocontrolled synthesis of spirocyclic compounds with heterocyclic fragments 99T9007. 

Stereocontrolled synthesis of polycyclic ethers and related heterocycles via intramolecular reactions of allylstannanes 97YGK619. 

Successive nucleophilic addition/ring closure (NARC) in stereocontrolled synthesis of heterocycles 97MI38. 

Stereocontrolled synthesis and recyclizations of C-acetylenylglycosides in the presence of dicobalt hexacarbonyl with formation of fused saturated 0-heterocyclic systems 98CC2665. 

Stereocontrolled synthesis of oxabicyclic (3-lactam antibiotics via [2- -2] cycloaddition of isocyanates to sugar vinyl ethers 96CC2689. 

Stereocontrolled synthesis of multifunctional bioactive 7-10-member 0-hetero-cycles 97YGK44. 

Stereocontrolled synthesis of thiosugars from acyclic precursors and preparation of pseudonucleosides with thiosugar moiety 97YGK186. 

The intramolecular cycloaddition of a nitrile oxide (a 1,3-dipole) to an alkene is ideally suited for the regio- and stereocontrolled synthesis of fused polycyclic isoxazolines.16 The simultaneous creation of two new rings and the synthetic versatility of the isoxa-zoline substructure contribute significantly to the popularity of this cycloaddition process in organic synthesis. In spite of its high degree of functionalization, aldoxime 32 was regarded as a viable substrate for an intramolecular 1,3-dipolar cycloaddition reaction. Indeed, treatment of 32 (see Scheme 17) with sodium hypochlorite... 

The intramolecular Heck reaction presented in Scheme 8 is also interesting and worthy of comment. Rawal s potentially general strategy for the stereocontrolled synthesis of the Strychnos alkaloids is predicated on the palladium-mediated intramolecular Heck reaction. In a concise synthesis of ( )-dehydrotubifoline [( )-40],22 Rawal et al. accomplished the conversion of compound 36 to the natural product under the conditions of Jeffery.23 In this ring-forming reaction, the a-alkenylpalladium(n) complex formed in the initial oxidative addition step engages the proximate cyclohexene double bond in a Heck cyclization, affording enamine 39 after syn /2-hydride elimination. The latter substance is a participant in a tautomeric equilibrium with imine ( )-40, which happens to be shifted substantially in favor of ( )-40. 

More functionalized 5,6-dihydro-2H-pyran-derivatives 71 and 72 have been prepared [26] by cycloaddition of 1 -methoxy-3-trialkylsilyloxy-1,3-butadienes 69 with t-butylglyoxylate (70) (Scheme 5.6). Whereas thermal reactions did not occur in good yields because of the decomposition of the cycloadducts, application of pressure (10 kbar) allowed milder conditions to be used, which markedly improved the reaction yields. The use of high pressure also gives preferentially en Jo-adduct allowing a stereocontrolled synthesis of a variety of substituted 5,6-dihydro-2H-pyran-derivatives, which are difficult to prepare by other procedures. 

Posner G. H. Stereocontrolled Synthesis of Functionalized Cyclohexenes Via Diels-Alder Cycloadditions of 2-Pyrones and 2-Pyridones-Applications to Synthesis of Physiologically Active Compounds in Stereocontrolled Org. Synth. 1994 177, Ed. Trost B. M., Pb. Blackwell Oxford... 

Guga P, Okruszek A, Stec WJ (2002) Recent Advances in Stereocontrolled Synthesis of P-Chiral Analogues of Biophosphates. 220 169-200... 

A highly stereocontrolled synthesis of (+) testosterone 49 was accomplished wherein the A/B ring system was constructed via INOC reaction of 47 to isox-azoline 48 (Scheme 6) [24]. The cycloaddition was assumed to be taking place via a chair-like TS 47 providing isomerically pure isoxazoline 48 in 87 % yield. 

CM has, in most cases, a good to excellent ii-selectivity. This is primarily due to steric reasons in the metallacycle intermediate of the metathesis. The high ii-selectivity of the CM makes it an ideal method for the stereocontrolled synthesis of stilbenes [152], while there is still no highly Z-selective Ru-based catalyst known [153]. 

In considering the retrosynthetic analysis of juvabione, two factors draw special attention to the bond between C(4) and C(7). First, this bond establishes the stereochemistry of the molecule. The C(4) and C(7) carbons are stereogenic centers and their relative configuration determines the diastereomeric structure. In a stereocontrolled synthesis, it is necessary to establish the desired stereochemistry at C(4) and C(7). The C(4)-C(7) bond also connects the side chain to the cyclohexene ring. As a cyclohexane derivative is a logical candidate for one key intermediate, the C(4)-C(7) bond is a potential bond disconnection. 

Recently, a new multicomponent condensation strategy for the stereocontrolled synthesis of polysubstituted tetrahydropyran derivatives was re-published by the Marko group, employing an ene reaction combined with an intramolecular Sakurai cyclization (IMSC) (Scheme 1.14) [14]. The initial step is an Et2AlCl-promoted ene reaction between allylsilane 1-50 and an aldehyde to afford the (Z)-homoallylic alcohol 1-51, with good control of the geometry of the double bond. Subsequent Lewis acid-media ted condensation of 1-51 with another equivalent of an aldehyde provided the polysubstituted exo-methylene tetrahydropyran 1-53 stereoselectively and... 

The use of silylketals derived from allylic alcohols and 1-substituted nitroethanols for the stereocontrolled synthesis of 3,4,5-trisubstituted 2-isoxazolines via intramolecular 1,3-dipolar cycloaddition has been demonstrated. Here again, the use of silyl nitronates (ISOC) increases the level of selectivity compared to INOC (Eq. 8.92).145... 

Dipolar addition to nitroalkenes provides a useful strategy for synthesis of various heterocycles. The [3+2] reaction of azomethine ylides and alkenes is one of the most useful methods for the preparation of pyrolines. Stereocontrolled synthesis of highly substituted proline esters via [3+2] cycloaddition between IV-methylated azomethine ylides and nitroalkenes has been reported.147 The stereochemistry of 1,3-dipolar cycloaddition of azomethine ylides derived from aromatic aldehydes and L-proline alkyl esters with various nitroalkenes has been reported. Cyclic and acyclic nitroalkenes add to the anti form of the ylide in a highly regioselective manner to give pyrrolizidine derivatives.148... 

M. Bols, Stereocontrolled synthesis of a glucosides by intramolecular glycosi-dation, J. Chem. Soc., Chem. Commun., 12 (1992) 913-914. 

An expedient and fully stereocontrolled synthesis of epothilones A (435, R = H) and B (435, R = Me) has been realized (473, 474). The routes described, involve an extensive study of nitrile oxide cycloadditions, as substitutes for aldol addition reactions, leading to the realization of a highly convergent synthesis, based on the Kanemasa hydroxyl-directed nitrile oxide cycloaddition. 

The opening of cyclopropylcarbinols to homoallylic bromides constituted the first use of cyclopropyl compounds for the stereocontrolled synthesis of natural products. The cyclopropyl conjunctive reagents enhance the richness of this notion. The stereocontrolled opening of vinylcyclopropanes by a homopentadienyl proton shift provides an approach to trisubstituted olefins and thereby a new strategy. The fungal prohormone methyl trisporate B (224) as summarized in Scheme 15 illustrates this conceptual development97). 

Indolizidine alkaloids. The key step in a new stereocontrolled synthesis of these alkaloids, such as castanospermine (5), depends upon the diastereoselective reaction of an azagluco aldehyde with allylmetal reagents catalyzed by Lewis acids (12, 21-22). Thus reaction of allyltrimethylsilane with the aldehyde 1 and TiCL, (excess) in CH2C12 at - 85° results in the product 2, formed by selective chelation of the ot-amino aldehydo group with TiCl4. The product can be converted into 5... 

The rearrangement provides a stereocontrolled synthesis of the C-pyranoside 2, present in pseudomonic acids.2... 

In the furanoside field, the introduction of the last two P-arabino units of a hexasaccharide motif from a bacterial cell wall arabinogalactan was achieved by the sulfoxide method with stereocontrol achieved because of the presence of the 2,3-anhydro group (Scheme 4.62) [368], More recently, the direct stereocontrolled synthesis of arabinofuranosides has been achieved by the sulfoxide method with the aid of a 3,5-0-(di-tert-butylsilylene)-protected donor [369]. 

This transformation opens a new access to enantiomerically pure l,3-oxazolidin-2-ones, a class of compounds which has been extensively studied either in medicinal chemistry85 87 or in stereocontrolled synthesis.11,12... 

The stereocontrolled synthesis of a chiral, polyhydroxy 1,7-dioxa-spiro[5.5]undecene from 2,3,4,6-tetra-O-benzyl-D-glucono-1,5-lactone... 

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