Diastereoselectivity compounds

Addition of A-mesityl benzimidazolyl carbene 720 to an a,/3-unsaturated aldehyde generates a homoenolate intermediate that undergoes an addition/acylation sequence with azomethine imine 719 to afford (3R, 5S, 6S )-177-pyrazolo[l,2- ]pyridazine-l,8(5//)-diones 721 with excellent diastereoselectivity. Compound 721 (Ar = R = Ph) treated with sodium hydoxide in methanol or benzylamine provided nearly quantitatively, ring-opened products 722a and 722b, respectively (Scheme 116) <2007JA5334>. 

In another failed approach, addition of 1-pyrrolidinocyclohexene 32 to ( )-( l-melhyl-2-oxoindolin-3-ylidene)acetophenone 31, followed by acid hydrolysis, could be controlled simply by changes in the reaction temperature, and was found to give diastereoselectively compounds 33 or 34. The latter compound was shown by NMR and X-ray diffraction data to have the suitable geometry to allow the creation of the crucial bond between the position adjacent to the cyclohexanone carbonyl and the oxindole C-4 position. 

The photolysis of nonchiral acyl azides such as compounds 45 [22] (Sch. 13), 27, 41, and 43 [22,45] (Sch. 12) in the presence of the substituted dihydropyranes (compound 104, used as a racemate) yields two diastereo-mers that can be characterized as 44exo- and 44endocompounds (105) according to the position of the five-membered ring in relation to the alkoxy substituent (see Sch. 30). The d.e. values are about 30% and are not affected by the size of the alkoxy group of the dihydropyran. In contrast, substituents present in benzoyl azides do influence the diastereoselectivity (compounds 41 15% 43 10%) [46]. 

The 1,3-anti-selective reduction was utilized in the total synthesis of the structurally unique compound (+)-clavosolide A (23)6 (Scheme 4.2g). The 1,5-anti -aldol reaction of a dibutylboron enolate of 24 with the aldehyde 25 proceeded smoothly to afford the (3-hydroxy ketone 26 in 93% yield and >96 4 diastereoselectivity. Compound 26 was subsequently treated with... 

The remarkable stereospecificity of TBHP-transition metal epoxidations of allylic alcohols has been exploited by Sharpless group for the synthesis of chiral oxiranes from prochiral allylic alcohols (Scheme 76) (81JA464) and for diastereoselective oxirane synthesis from chiral allylic alcohols (Scheme 77) (81JA6237). It has been suggested that this latter reaction may enable the preparation of chiral compounds of complete enantiomeric purity cf. Scheme 78) ... 

There has been recent interest in naphtho-fused dithiepines as chiral acyl anion equivalents, particularly since the starting dithiol 128 can be obtained in enan-tiomerically pure form (89TL2575). This is transformed using standard methods into the dithiepine 129, but showed only moderate diastereoselectivity in its addition to carbonyl compounds. On the other hand, as we have seen previously for other systems, formation of the 2-acyl compound 130 and reduction or addition of a Grignard reagent gave the products 131 with much better stereoselectivity (91JOC4467). 

The validity of the model was demonstrated by reacting 35 under the same reaction conditions as expected, only one diastereoisomer 41 was formed, the structure of which was confirmed by X-ray analysis. When the vinylation was carried out on the isothiazolinone 42 followed by oxidation to 40, the dimeric compound 43 was obtained, showing that the endo-anti transition state is the preferred one. To confirm the result, the vinyl derivative 42 was oxidized and the intermediate 40 trapped in situ with N-phenylmaleimide. The reaction appeared to be completely diastereoselective and a single diastereomer endo-anti 44 was obtained. In addition, calculations modelling the reactivity of the dienes indicated that the stereochemistry of the cycloaddition may be altered by variation of the reaction solvent. 

Danishefsky s diene 154 DBFOX 232 dendrimers 229 DPT calculations 308 diacetone glucose derived-titanium(IV) 178 diastereoselectivity 216 diazo compounds 242 diazoalkane cycloadditions 278 diazoalkanes 213, 231 (R,R)-4,6-dibenzofurandiyl-2,2 -bis(4-phenylox-azoline) 250... 

The stereochemical outcome of the Michael addition reaction with substituted starting materials depends on the geometry of the a ,/3-unsaturated carbonyl compound as well as the enolate geometry a stereoselective synthesis is possible. " Diastereoselectivity can be achieved if both reactants contain a stereogenic center. The relations are similar to the aldol reaction, and for... 

The diastereoselectivity is observed in the Henry reaction using optical active niti o compounds or a-heteroatom substituted aldehydes. Lor example, the reaction of O-benzyl-D-lactal-dehyde with methyl 3-niti opropionate in the presence of neubal alumina leads to a mixture of three niti o-aldol products from which D-ribo isomer is isolated by direct crystallization. D-Ribo... 

The synthetic problem is now reduced to cyclopentanone 16. This substance possesses two stereocenters, one of which is quaternary, and its constitution permits a productive retrosynthetic maneuver. Retrosynthetic disassembly of 16 by cleavage of the indicated bond furnishes compounds 17 and 18 as potential precursors. In the synthetic direction, a diastereoselective alkylation of the thermodynamic (more substituted) enolate derived from 18 with alkyl iodide 17 could afford intermediate 16. While trimethylsilyl enol ether 18 could arise through silylation of the enolate oxygen produced by a Michael addition of a divinyl cuprate reagent to 2-methylcyclopentenone (19), iodide 17 can be traced to the simple and readily available building blocks 7 and 20. The application of this basic plan to a synthesis of racemic estrone [( >1] is described below. 

Our journey begins with the photo-induced union of 3,4-dimethylfuran (19) and / -(benzyloxy)-propanal (18) (see Scheme 5). Irradiation of a solution of these two simple, achiral compounds in benzene with a 450 W Hanovia lamp equipped with a vycor filter results in the exclusive formation of head-to-head, exo photoadduct 17 in 63% yield. As a cw-fused dioxabicyclo[3.2.0]heptene system, intermediate 17 possesses a folded molecular framework to which access is obstructed on the concave face. In the presence of mCPBA, the less hindered convex face of the enol ether double bond is oxidized in a completely diastereoselective fashion, affording intermediate 16 in 80% yield after regioselective opening of... 

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