N-Facial diastereoselectivity

A non-biomimetic synthesis of /J-(-)-horsfiline (57) has also been recently reported which was based on a thermal intermolecular 1,3-dipolar cycloaddition reaction as outlined in Scheme 7 [63J. The reaction of the optically active menthyl ester 67 acting as a dipolarophile, with the JV-methylazomethine ylide 68 (thermally generated in situ from sarcosine and formaldehyde) proceeded with n-facial diastereoselectivity to produce a chromatographically separable mixture of 69 and the unwanted diastereomer. Subsequent cleavage of the chiral auxiliary, followed by removal of the carboxylic acid group by the Barton radical method provided J7-(-)-horsfiline. 

Cieplak AS, Tail BD, Johnson CR (1989) Reversal of n-facial diastereoselection upon electronegative substitution of the substrate and the reagent. J Am Chem Soc 111 8447-8462... 

Frenking, G., Kdhler, K. R, Reetz, M. T. (1991). On the Origin of n-Facial Diastereoselectivity in Addition Reactions of Cyclohexane-Based Systems. Angewandte Chemie International Edition in English, 30(9), 1146-1149. 

Tetraene 141 has been converted into various complex polycondensed adducts by reacting with a variety of dienophiles such as maleic anhydride, N-phenylmaleimide, N-phenyltriazolinedione,p-benzoquinone and tetracyano-ethylene carried out under thermal conditions. All cycloadditions occurred facial-diastereoselectively from an outside attack and provided monocycloadducts which had an exceptionally close relationship between diene and dieno-phile and then underwent intramolecular cycloaddition [125]. The reaction between 141 and p-benzoquinone is illustrated in Scheme 2.53. 

A systematic study of methyl ketone aldol additions with a-alkoxy and o ,/5-bisalkoxy aldehydes has been undertaken, under non-chelating conditions.130 With a single a-alkoxy stereocentre, diastereoselectivity generally follows Cornforth/polar Felkin-Anh models. With an additional /5-alkoxy stereocentre, 7r-facial selectivity is dramatically dependent on the relative configuration at a- and /3-centres if they are anti, high de results, but not if they are syn. A model for such acyclic stereocontrol is proposed in which the /5-alkoxy substituent determines the position in space of the a-alkoxy relative to the carbonyl, thus determining the n-facial selectivity. 

Steric factors have been shown to be important in controlling the face sensitivities in 4 + 2-cycloadditions of diastereotopically non-equivalent n -facial 1,6-annulated-cyclohexa-1,3-dienes.102 The diastereoselectivity of the Diels-Alder reactions of l-(f-butyldimethylsiloxy)buta-1,3-diene with C(2) symmetric tartrate-derived dienophiles... 

In order to justify the stereochemistry of the major adducts 155, the authors proposed that they result from an exclusive endo approach toward the less hindered face of the diene (opposite to the p-tolyl group), with the sulfinyl group adopting the s-trans conformation with respect to the C(l)-C(2) double bond (B in Fig. 13). Nevertheless, this conformational preference is not rationalized in the paper. Aversa et al. [137c] have recently reported that uncatalyzed reactions of (Rs)-152 with maleimide and N-phenyl maleimide occurred with complete endo- and very high facial diastereoselectivities. In this sense, the results ob-... 

CONTENTS Facial Diastereoselection in Diels-Alder Cycloadditions and Related Reactions Understanding Planar Interactions and Establishing Synthetic Potential, A. G. Faille and Yee-Fung Lu. Substituent and Structural Effects in the Ozonolysis of Cyclic Vinylogous Esters. W. H. Bunnelle. N-Metalated Azomethine Ylides, S. Kanemasa and Otohiko Tsuge. Azomethine Ylide Cy-cloadditlons via 1,2- Prototropy and Metallo-Dipole Formation from Imines, R. Grigg and V. Sridharan. Index. 

Bach, T, Schroder, J., Brandi, T, Hecht, J., and Harms, K., Facial diastereoselectivity in the photocycloaddition of chiral N-acyl enamines to benzaldehyde. Tetrahedron, 54,4507,1998. 

Until now, only few efforts were undertaken to control the configurate of the new asymmetric centers and to obtain optical pure products from the [3 photocycloaddition. In one attempt, enantiomerically pure starting material was used for the photochemical reaction (Scheme 33) [86]. The chiral informal fixed in the y position of the olefinic side chain permits a high facial (exo/en< differentiation for the 1,3-attack (transition state N). The high diastereoselect ... 

Remote stereocentres have been shown to influence the facial preference for the diastereoselective protonation of enolates. Deprotonation of an equimolar diastereoisomeric mixture of 5-lactams (a-S, N-R)-143 and (a-R, N-R)-143 with -BuLi, followed by the... 

Mapp et al. have reported a versatile and efficient synthesis of substituted P-amino acids (P-AA) through diastereoselective nucleophilic addition to enantiopure isoxazolines 40. In the C=N reduction with LiAlILt in THF, the proximal hydroxymethyl substituent directed the hydride approach to the same side as the C-5 ring substituent, affording the amino diol 41 with high diastereoselectivity. In contrast, carbon nucleophiles were sterically driven and preferentially added on the opposite isoxazoline face. The facial selectivity was complete with... 

Nitrones have also been used as electrophiles toward 67, though the diastereo-selectivities of the reactions were less satisfactory than those with the corresponding imines [59,60]. Addition of one equivalent of the lithium salt of quini-dine (72) improves the diastereoselectivity dramatically for various 3,4-dihydr-oisoquinohne N-oxides 71 (Scheme 21) [60]. The formation of a facial discrimi-... 

Asymmetric aldol reactions. The chiral N-propionyloxazolidinone (1), prepared in several steps from (lR)-(—)-camphorquinone, undergoes highly diastereoselective aldol reactions with the additional advantage of high crystallinity for improving the optical purities of crude aldols. Either the lithium enolate or the titanium enolate, prepared by transmetalation with ClTi(0-(-Pr)3, reacts with aldehydes to form syn-adducts with diastereomeric purities of 98-99% after one crystallization. The observed facial selectivity is consistent with metal chelation of intermediate (Z)-enolates (supported by an X-ray crystal structure of the trapped silyl enol ether). The lithium enolate also exhibits... 

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