Pseudoaxial position

Propenyl)-1,3-dithiane, after lithiation and addition of zinc chloride, reacts with ethyl 2-oxopropanoate to give preferentially the. vvn-adduct37, which is an intermediate in the synthesis of racemic /ra .s-tetrahydro-2,3-dimethyl-5-oxo-2-furancarboxylic acid. It is assumed, that the ethoxycarbonyl group is brought to a pseudoaxial position in the cyclic transition state by the chelating zinc cation. 

C-Alkylations of l,4-dihydro-27/-pyrazino[2,l-A]quinazoline-3,6-diones at positions C-l and CM were studied in detail. Compounds of type 57 could be alkylated diastereoselectively at C-l, owing to the geometry of the piperazine ring, which is locked in a flat boat conformation with the R4 or R1 substituent in a pseudoaxial position to avoid steric interaction with the nearly coplanar C(6)-carbonyl group. Alkylation of 57 (R2 = Me, Bn, R4 = Me) in the presence of lithium hexamethyldisilazide (LHMDS) with benzyl and allyl halides resulted, under kinetic control, in the 1,4-trans-diastereomer 59 as the major product, with retention of the stereocenter at CM (Scheme 5). 

The cyclobutanone 105, on thermolysis at 190°C, undergoes a retro-ene reaction yielding the crystalline 0,y-unsaturated ketone 115. This product in the solid regenerates 105 photochemically, in almost quantitative yield, whereas in solution the diketone 116 is the exclusive photoproduct. The ketone 115 is found in the solid to have the conformation 115a, a conformation that results, presumably, from the requirement for the bulky methyl at C-7 to adopt the pseudo-equatorial rather than the pseudoaxial position. This molecule in fact has a shape... 

The formation of the products could be explained by hemiacetal formation followed by Prins cyclization and subsequent Ritter amidation. A tentative reaction mechanism to realize the cis selectivity is given in Fig. 20 and could be explained by assuming the formation of an (L )-oxocarbenium ion via a chair-like transition state, which has an increased stability relative to the open oxocarbenium ion owing to electron delocalization. The optimal geometry for this delocalization places the hydrogen atom at C4 in a pseudoaxial position, which favors equatorial attack of the nucleophiles. 

Two possibilities can be distinguished with compound 10 for an exo-E-anti transition state the methyl group might occupy either a pseudoequatorial or a pseudoaxial position. Product 11a arises from the energetically more favorable state 20a, whereas lib is derived from transition state 20b. It is in this way that the methyl group of citronellal (9) determines the ratio of 20a to 20b. 

Conformational analysis of some 9-chloro- and 9-bromo-6,7,8,9-tetrahy-dro-4//-pyrido[ 1,2-a]pyrimidin-4-ones 31 and their 9,9-dichloro and 9,9-dibromo derivatives was also carried out by I3C NMR spectroscopy (83JHC619). The halogen atoms in the 9-chloro and 9-bromo derivatives 31 (R = H) in the predominantly half-chair conformation occupy the pseudoaxial position. This conformer is probably stabilized by a favorable orbital interaction, while the other one, with a presudoequatorial halogen atom, is destabilized by the unfavorable dipole-dipole interaction between the 9-halogen and C(9a)=N(l) bonds. The methyl group in the 6-methyl derivatives in predominantly half-chair conformations is in the pseudoaxial position (83JHC619). 

For 9-phenylamino-6,7,8,9-tetrahydro-4//-pyrido[l,2-a]pyrimidin-4-ones 32 (R = NHPh R1 = H R2 = H, COOH) the half-chair conformation with a pseudoaxial 9-phenylamino group was the predominant one. But with the 6-methyl-9-phenylamino derivatives 32 (R = NHPh, R1 = Me) the cis-trans ratio was near 1 1 in the imine form. The presence of a methyl group on the nitrogen atom of the 9-anilino group 32 (R = NMePh) increased the amount of the cis form which contained the 9-substituent in a pseudoequatorial position [85JCS(P1)1015]. The 6-methyl group was in a pseudoaxial position in all tautomers. 

Another significant deviation from known rules has been observed in the rather low affinity of K+ with the 1,10-diaza crown 18-C-6 with only AG=10 kJ/mol (in methanol). It has been shown that the free energy of binding AG in crown ether and ciyptand complexes usually is an additive function of number and electron donicity of the host donor atoms which are in contact with the metal ion.[17] Molecular mechanics calculations suggest the reduced affinity with the diazacrown to be due to the N-lone pairs in pseudoaxial position, pointing away from the metal ion (Figure 4). This has led to experiments with the N-methyl substituted crown here the N-alkyl substituents would clash which each other inside the macrocycle, therefore a pseudoequatorial lone pair orientation towards the cation is enforced, and the stability of the complex indeed returns to the normal scale with an increase to 29.5 kJ/mol.[ 18]... 

Single crystal X-ray diffraction data for disubstituted 1,3,2-dioxathiolane V-oxides 12 (R = c-C6Hn) <1995AXC129>, 12 (R = Ph), 13, and 14 <1996AXC739> revealed half-chair (envelope) conformations of the five-membered cycles with the S=0 group in a pseudoaxial position and other substituents in pseudoequatorial positions. 

Tetronates derived from l,3-divinyl-2-cyclopentanol were employed to study the possibility of a differentiation of enantiotopic or diastereotopic double bonds in their [2 + 2]-photocydoaddition [140]. It was found that tetronate 148 underwent a selective [2 + 2]-photocydoaddition (r.r. = 75/25) at one of the two possible double bonds to deliver product 149 in 67% yield (Scheme 6.52). The reaction was analyzed regarding the preferred conformations of the cyclopentanol, with the notion that the tetronate resides in a pseudoequatorial position, and the vinyl group in a pseudoaxial position of the envelope conformation. Intermediate 149 served as starting material for the first total synthesis of the tetracydic sesquiterpene (T)-punctaporonin C (150) [141]. 

The ring was built up from a cetyl a ted (S)-lactic acid, and a cy clization step introduced the second chiral centre—the methyl group goes pseudoequatorial while the pseudoaxial position is preferred by the methoxy group because of the anomeric effect (Chapter 42). 

Fig.1 The molecular geometry of DHP analogues. This geometry was adopted by Gaudio et al. to calculate some quantum mechanical parameters, which they used in their QSAR study [16]. The 1,4-dihydropyridine ring is shown to have a boat-like conformation and the phenyl ring to be bound to it at a pseudoaxial position and approximately bisecting the pyridine ring. From [16]. 1994 John Wiley Sons, Inc., reprinted by permission...

This is readily explained by torsional interactions, which force the encfo-substituent into a pseudoaxial position trans to the partially formed C-0 bond. The steric interaction of the substituent with the second pseudoaxial substituent, even with hydrogen, is then stronger than that of a pseudoequatorial substituent with the transferred oxygen. 

Surprisingly, neoalloocimene (18) is more reactive than alloocimene (16) toward phthalazine-1,4-dionc and benzo[g]phthalazine-l,4-dione, generated in situ by oxidation of the corresponding cyclic hydrazides with lead tetraacetate or tm-butyl hypochlorite, the civ-adducts 21 and 22 are predominantly obtained from either of the isomeric trienes37. The II-NMR spectra of the predominant isomers shows the C-l and C-4 substituents occupying pseudoaxial positions. 

From examination of the HNMR spectra of 5-alkoxy- and 5-hydroxy-A -l,2,3-triazo-lines, an envelope conformation of the molecule was deduced with the 5-substituent being in a pseudoaxi position at the flap and the 1-substituent being pseudoequatorial. This preferred conformation can originate a type of anomeric effect (74ACS(B)425). 5-Amino-l-(p-nitrophenyl)-A -l,2,3-triazolines have also been found to prefer the envelope conformation (74ACS(B)425>. 

The preferred orientation of the alkyl substituent in 9-alkyl-9,10-dihydroanthracenes is the pseudoaxial position (Me and Ph substituents occupy a pseudoequatorial position to some extent) (50), and the alkyl groups occupy the diaxial positions in m-9,10-dihydroanthracene derivatives (292). The favored conformation of the 10-substituted 10,H-dihydrodibenz[i,/]oxepins is that in which the 10-substituent is quasi-equatorial with respect to the seven-membered ring (187). In a study of the cis- and trawr-thioxanthenes, the lone pair was found to prefer the axial position (324) ... 

The solvent exerts a strong influence on the product distribution. Starting from the same tetrahydrobenzylisoquinoline in MeCN, 82% XXXV are fonned. In MeCN-MeOH the intermediate can be effectively trapped by methanolysis and 58% XXXVI are obtained [159]. A major mechanistic study seeking common denominators in the oxidations leading to XXIV, XXVI, and XXVIII has been published [152b]. A stereochemical study indicated that the yield in the cyclization is independent on the pseudoequatorial or pseudoaxial position of the benzyl substituent in the benzyltetrahy-droisoquinoline [160]. 

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