Acetals stereochemistry

These characteristic resonances were used by the authors <1997SPL241> to assign the acetal stereochemistry in a number of other 1,2,4-trioxanes. 

Diacetoxylation of various conjugated dienes including cyclic dienes has been extensively studied. 1,3-Cyclohexadiene was converted into a mixture of isomeric l,4-diacetoxy-2-cyclohexenes of unknown stereochemistry[303]. The stereoselective Pd-catalyzed 1,4-diacetoxylation of dienes is carried out in AcOH in the presence of LiOAc and /or LiCI and beiizoquinone[304.305]. In the presence of acetate ion and in the absence of chloride ion, /rau.v-diacetox-ylation occurs, whereas addition of a catalytic amount of LiCl changes the stereochemistry to cis addition. The coordination of a chloride ion to Pd makes the cis migration of the acetate from Pd impossible. From 1,3-cyclohexadiene, trans- and ci j-l,4-diacetoxy-2-cyclohexenes (346 and 347) can be prepared stereoselectively. For the 6-substituted 1,3-cycloheptadiene 348, a high diaster-eoselectivity is observed. The stereoselective cij-diacetoxylation of 5-carbo-methoxy-1,3-cyclohexadiene (349) has been applied to the synthesis of dl-shikimic acid (350). 

It is possible to prepare 1-acetoxy-4-chloro-2-alkenes from conjugated dienes with high selectivity. In the presence of stoichiometric amounts of LiOAc and LiCl, l-acetoxy-4-chloro-2-hutene (358) is obtained from butadiene[307], and cw-l-acetoxy-4-chloro-2-cyclohexene (360) is obtained from 1.3-cyclohexa-diene with 99% selectivity[308]. Neither the 1.4-dichloride nor 1.4-diacetate is formed. Good stereocontrol is also observed with acyclic diene.s[309]. The chloride and acetoxy groups have different reactivities. The Pd-catalyzed selective displacement of the chloride in 358 with diethylamine gives 359 without attacking allylic acetate, and the chloride in 360 is displaced with malonate with retention of the stereochemistry to give 361, while the uncatalyzed reaction affords the inversion product 362. 

The wM-diacetate 363 can be transformed into either enantiomer of the 4-substituted 2-cyclohexen-l-ol 364 via the enzymatic hydrolysis. By changing the relative reactivity of the allylic leaving groups (acetate and the more reactive carbonate), either enantiomer of 4-substituted cyclohexenyl acetate is accessible by choice. Then the enantioselective synthesis of (7 )- and (S)-5-substituted 1,3-cyclohexadienes 365 and 367 can be achieved. The Pd(II)-cat-alyzed acetoxylactonization of the diene acids affords the lactones 366 and 368 of different stereochemistry[310]. The tropane alkaloid skeletons 370 and 371 have been constructed based on this chemoselective Pd-catalyzed reactions of 6-benzyloxy-l,3-cycloheptadiene (369)[311]. 

The reaction of phenylzinc reagent proceeds with opposite stereochemistry, namely by retention of configuration at the final step via transmetallation. Both the (S)-( )- and (i )-(Z)-allylic acetates 4 and 9 afford the (/ )-( )-phe-nylated product II by overall inversion[23]. 

Based on the above-mentioned stereochemistry of the allylation reactions, nucleophiles have been classified into Nu (overall retention group) and Nu (overall inversion group) by the following experiments with the cyclic exo- and ent/n-acetales 12 and 13[25], No Pd-catalyzed reaction takes place with the exo-allylic acetate 12, because attack of Pd(0) from the rear side to form Tr-allyl-palladium is sterically difficult. On the other hand, smooth 7r-allylpalladium complex formation should take place with the endo-sWyWc acetate 13. The Nu -type nucleophiles must attack the 7r-allylic ligand from the endo side 14, namely tram to the exo-oriented Pd, but this is difficult. On the other hand, the attack of the Nu -type nucleophiles is directed to the Pd. and subsequent reductive elimination affords the exo products 15. Thus the allylation reaction of 13 takes place with the Nu nucleophiles (PhZnCl, formate, indenide anion) and no reaction with Nu nucleophiles (malonate. secondary amines, LiP(S)Ph2, cyclopentadienide anion). 

It was claimed that the Z-form of the allylic acetate 430 was retained in homoallylic ketone 431 obtained by reaction with the potassium enolate of 3-vinylcyclopentanone (429), after treatment with triethylborane[282]. Usually this is not possible. The reaction of a (Z)-allylic chloride with an alkenylaluminum reagent to give 1,4-dienes proceeds with retention of the stereochemistry to a considerable extent when it is carried out at -70 C[283]. 

The reaction of the allylic acetate with a diene system 784 affords the poly-fused ring system 785 by three repeated alkene insertions[487]. An even more strained molecule of the [5.5.5.5] fenestrane 788 has been constructed by a one-pot reaction in a satisfactory yield by the Pd-catalyzed carbonylation-cycliza-tion of 786 without undergoing elimination of /3-hydrogen in the cr-alkylpalla-dium intermediate 787 owing to unfavorable stereochemistry for syn elimination[488]. 

This chapter is divided into two parts The first and major portion is devoted to carbohydrate structure You will see how the principles of stereochemistry and confer matronal analysis combine to aid our understanding of this complex subject The remain der of the chapter describes chemical reactions of carbohydrates Most of these reactions are simply extensions of what you have already learned concerning alcohols aldehydes ketones and acetals... 

Several electrophiles, such as acetic anhydride, nitric acid or alternative nitrating agents, such as ammonium nitrate in trifluoroacetic anhydride (41), or sodium hypochlorite, react at N-1, which is followed by reaction at N-3 under suitable conditions. In the case of acetic anhydride, the reaction can take place exclusively at N-3 if N-1 is hindered this fact has served as a criterion for studying the stereochemistry of 5-spirohydantoin derivatives (42,43). 

Reaction of acetic acid and a catalytic amount of sulfuric acid at reflux temperatures for 6—8 hours with dihydromyrcene can cause rearrangement of the dihydromyrcenyl acetate to give a mixture of the cycHc acetates analogous to the cycHc formate esters (108). The stereochemistry has also been explained for this rearrangement, depending on whether (+)- or (—)-dihydromyrcene is used (109). The cycHc acetates are also commercially avaUable products known as Rosamusk and CyclocitroneUene Acetate. 

The poly(vinyl alcohol) made for commercial acetalization processes is atactic and a mixture of cis- and /n j -l,3-dioxane stereoisomers is formed during acetalization. The precise cis/trans ratio depends strongly on process kinetics (16,17) and small quantities of other system components (23). During formylation of poly(vinyl alcohol), for example, i j -acetalization is more rapid than /ra/ j -acetalization (24). In addition, the rate of hydrolysis of the trans-2iQ. -A is faster than for the <7 -acetal (25). Because hydrolysis competes with acetalization during acetal synthesis, a high cis/trans ratio is favored. The stereochemistry of PVF and PVB resins has been studied by proton and carbon nmr spectroscopy (26—29). 

A wide variety of /3-lactams are available by these routes because of the range of substituents possible in either the ketene or its equivalent substituted acetic acid derivative. Considerable diversity in imine structure is also possible. In addition to simple Schiff bases, imino esters and thioethers, amidines, cyclic imines and conjugated imines such as cinnamy-lidineaniline have found wide application in the synthesis of functionalized /3-lactams. A-Acylhydrazones can be used, but phenylhydrazones and O-alkyloximes do not give /3-lactams. These /3-lactam forming reactions give both cis and /raMS-azetidin-2-ones some control over stereochemistry can, however, be exercised by choice of reactants and conditions. 

Although ethereal solutions of methyl lithium may be prepared by the reaction of lithium wire with either methyl iodide or methyl bromide in ether solution, the molar equivalent of lithium iodide or lithium bromide formed in these reactions remains in solution and forms, in part, a complex with the methyllithium. Certain of the ethereal solutions of methyl 1ithium currently marketed by several suppliers including Alfa Products, Morton/Thiokol, Inc., Aldrich Chemical Company, and Lithium Corporation of America, Inc., have been prepared from methyl bromide and contain a full molar equivalent of lithium bromide. In several applications such as the use of methyllithium to prepare lithium dimethyl cuprate or the use of methyllithium in 1,2-dimethyoxyethane to prepare lithium enolates from enol acetates or triraethyl silyl enol ethers, the presence of this lithium salt interferes with the titration and use of methyllithium. There is also evidence which indicates that the stereochemistry observed during addition of methyllithium to carbonyl compounds may be influenced significantly by the presence of a lithium salt in the reaction solution. For these reasons it is often desirable to have ethereal solutions... 

Nucleophilic substitution in cyclohexyl systems is quite slow and is often accompanied by extensive elimination. The stereochemistry of substitution has been determined with the use of a deuterium-labeled substrate (entry 6). In the example shown, the substitution process occurs with complete inversion of configuration. By NMR amdysis, it can be determined that there is about 15% of rearrangement by hydride shift accon any-ing solvolysis in acetic acid. This increases to 35% in formic acid and 75% in trifiuoroacetic acid. The extent of rearrangement increases with decreasing solvent... 

Evidently, since there is no appreciable rate acceleration, this participatimi is not very strong at the transition state. Nevertheless, the participation is strong enough to control stereochemistry. When mote nucleophilic solvents are used (e.g., acetic acid), participation is not observed, and the product is 100% of inverted configuration. 

Furthermore, the stereochemistry of the product 1 changes as the solvent is changed. In aqueous dioxane, the reaction proceeds with complete inversion, but in 1,1,1,3,3,3 hexafluoro-2-propanol with 100% retention. In acetic acid, the reaction occurs mainly with inversion (83%), but in formic acid the amount of retention (40%) is comparable to the amount of inversion (60%). Discuss these results, particularly with respect to the change of product composition and stereochemistry as a function of solvent. 

Alkynes react with mercuric acetate in acetic acid to give addition products. In the case of 3-hexyne, the product has -stereochemistry, but the Z-isomer is isolated from diphenylacetylene. The kinetics of the addition reaction are first-order in both alkyne and... 

Benzene-sensitized photolysis of methyl 3-cyclohexene-1-carboxylate in acetic acid leads to addition of acetic acid to the double bond. Only the trans adducts are formed. What factor(s) is (are) responsible for the reaction stereochemistry Which of the two possible addition products, A or B, do you expect to be the major product ... 

Partial Synthesis of a-Amyrin Acetate Proof of the Structure and Stereochemistry... 

Protonation of the a-carbanion (50), which is formed both in the reduction of enones and ketol acetates, probably first affords the neutral enol and is followed by its ketonization. Zimmerman has discussed the stereochemistry of the ketonization of enols and has shown that in eertain cases steric factors may lead to kinetically controlled formation of the thermodynamically less stable ketone isomer. Steroidal unsaturated ketones and ketol acetates that could form epimeric products at the a-carbon atom appear to yield the thermodynamically stable isomers. In most of the cases reported, however, equilibration might have occurred during isolation of the products so that definitive conclusions are not possible. 

In a study of the stereochemistry of the B-homosteroid ring system, Kohout, Fajkos and Sorm prepared 3 -hydroxy-B-homo-5a-cholestan-7-one acetate... 

The results observed in the oxidation of alkaloids which indicated something of the stereochemistry required for oxidation and prompted studies on model systems can now be interpreted more confidently. However, care must be used when basing steric differentiation on mercuric acetate oxidation studies since conditions must be employed which avoid epimerization at carbons alpha to the nitrogen. 

The most general method for synthesis of cyclic enamines is the oxidation of tertiary amines with mercuric acetate, which has been investigated primarily by Leonard 111-116) and applied in numerous examples of structural investigation and in syntheses of alkaloids 102,117-121). The requirement of a tram-coplanar arrangement of an a proton and mercury complexed on nitrogen, in the optimum transition state, confers valuable selectivity to the reaction. It may thus be used as a kinetic probe for stereochemistry as well as for the formation of specific enamine isomers. 

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