Stereochemistry formation

All of the photochemical cycloaddition reactions of the stilbenes are presumed to occur via excited state ir-ir type complexes (excimers, exciplexes, or excited charge-transfer complexes). Both the ground state and excited state complexes of t-1 are more stable than expected on the basis of redox potentials and singlet energy. Exciplex formation helps overcome the entropic problems associated with a bimolecular cycloaddition process and predetermines the adduct stereochemistry. Formation of an excited state complex is a necessary, but not a sufficient condition for cycloaddition. In fact, increased exciplex stability can result in decreased quantum yields for cycloaddition, due to an increased barrier for covalent bond formation (Fig. 2). The cycloaddition reactions of t-1 proceed with complete retention of stilbene and alkene photochemistry, indicative of either a concerted or short-lived singlet biradical mechanism. The observation of acyclic adduct formation in the reactions of It with nonconjugated dienes supports the biradical mechanism. 

Inversion of configuration requires that the nucleophile adds electrons to die a orbital of die carbon-tridate bond from die side opposite diat bond. As required by die stereochemistry, formation of die bond from azide to carbon is concurrent widi cleavage of the carbon leaving group bond. 

The product is racemic because the two intermediates have planes of symmetry and are achiral. The retention of relative stereochemistry (formation of trans product from trans starting material) could result from stereoselective recombination (the two faces of the allylic cation are not the same) or from the two ions sticking together as an ion pair so that the acetate anion slides across the cation... 

Aldol Product Stereochemistry Depends on Enolate Stereochemistry FORMATION OF ( ) AND (Z) ENOLATES... 

Turro N J, Buchachenko A L and Tarasov V F 1995 How spin stereochemistry severely complicates the formation of a carbon-carbon bond between two reactive radicals in a supercage Acc. Chem. Res. 28 69-80... 

Tabic 2-6 gives an overview on the most common file formats for chemical structure information and their respective possibilities of representing or coding the constitution, the configuration, i.c., the stereochemistry, and the 3D structure or conformation (see also Sections 2..3 and 2.4). Except for the Z-matrix, all the other file formats in Table 2-6 which are able to code 3D structure information arc using Cartesian coordinates to represent a compound in 3D space. 

Stereochemistry can be represented graphically in 2D structures, but also by (permutations) descriptors. It is included in all line notations and exchange formats. 

Cyclopentene derivatives with carboxylic acid side-chains can be stereoselectively hydroxy-lated by the iodolactonization procedure (E.J. Corey, 1969, 1970). To the trisubstituted cyclopentene described on p. 210 a large iodine cation is added stereoselectively to the less hindered -side of the 9,10 double bond. Lactone formation occurs on the intermediate iod-onium ion specifically at C-9ot. Later the iodine is reductively removed with tri-n-butyltin hydride. The cyclopentane ring now bears all oxygen and carbon substituents in the right stereochemistry, and the carbon chains can be built starting from the C-8 and C-12 substit""" ... 

In his cephalosporin synthesis methyl levulinate was condensed with cysteine in acidic medium to give a bicyclic thiazolidine. One may rationalize the regioselective formation of this bicycle with the assumption that in the acidic reaction mixture the tMoI group is the only nucleophile present, which can add to the ketone. Intramolecular amide formation from the methyl ester and acid-catalyzed dehydration would then lead to the thiazolidine and y-lactam rings. The stereochemistry at the carboxylic acid a-... 

Formation of a Tr-allylpalladium complex 29 takes place by the oxidative addition of allylic compounds, typically allylic esters, to Pd(0). The rr-allylpal-ladium complex is a resonance form of ir-allylpalladium and a coordinated tt-bond. TT-Allylpalladium complex formation involves inversion of stereochemistry, and the attack of the soft carbon nucleophile on the 7r-allylpalladium complex is also inversion, resulting in overall retention of the stereochemistry. On the other hand, the attack of hard carbon nucleophiles is retention, and hence Overall inversion takes place by the reaction of the hard carbon nucleophiles. 

The stereochemistry of the Pd-catalyzed allylation of nucleophiles has been studied extensively[5,l8-20]. In the first step, 7r-allylpalladium complex formation by the attack of Pd(0) on an allylic part proceeds by inversion (anti attack). Then subsequent reaction of soft carbon nucleophiles, N- and 0-nucleophiles proceeds by inversion to give 1. Thus overall retention is observed. On the other hand, the reaction of hard carbon nucleophiles of organometallic compounds proceeds via transmetallation, which affords 2 by retention, and reductive elimination affords the final product 3. Thus the overall inversion is observed in this case[21,22]. 

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). 

The reaction of vinyloxiranes with malonate proceeds regio- and stereose-lectively. The reaction has been utilized for the introduction of a 15-hydroxy group in a steroid related to oogoniol (265)(156]. The oxirane 264 is the J-form and the attack of Pd(0) takes place from the o-side by inversion. Then the nucleophile comes from the /i-side. Thus overall reaction is sT -StM2 type, in the intramolecular reaction, the stereochemical information is transmitted to the newly formed stereogenic center. Thus the formation of the six-membered ring lactone 267 from 266 proceeded with overall retention of the stereochemistry, and was employed to control the stereochemistry of C-15 in the prostaglandin 268[157]. The method has also been employed to create the butenolide... 

The Pd-catalyzed hydrogenolysis of vinyloxiranes with formate affords homoallyl alcohols, rather than allylic alcohols regioselectively. The reaction is stereospecific and proceeds by inversion of the stereochemistry of the C—O bond[394,395]. The stereochemistry of the products is controlled by the geometry of the alkene group in vinyloxiranes. The stereoselective formation of stereoisomers of the syn hydroxy group in 630 and the ami in 632 from the ( )-epoxide 629 and the (Z)-epoxide 631 respectively is an example. 

Aldoses exist almost exclusively as their cyclic hemiacetals very little of the open chain form is present at equilibrium To understand their structures and chemical reac tions we need to be able to translate Fischer projections of carbohydrates into their cyclic hemiacetal forms Consider first cyclic hemiacetal formation m d erythrose To visualize furanose nng formation more clearly redraw the Fischer projection m a form more suited to cyclization being careful to maintain the stereochemistry at each chirality center... 

Generating Haworth formulas to show stereochemistry m furanose forms of higher aldoses is slightly more complicated and requires an additional operation Furanose forms of D ribose are frequently encountered building blocks m biologically important organic molecules They result from hemiacetal formation between the aldehyde group and the C 4 hydroxyl... 

X-Ray Diffraction. Because of the rapid advancement of computer technology (qv), this technique has become almost routine and the stmctures of moderately complex molecules can be estabUshed sometimes in as Htde as 24 hours. An example illustrating the method is offered by Reference 24. The reaction of the acrylate (20) with phenyldiazo derivatives results in the formation of pyrazoline (21). The stereochemistry of the substituents and the conformation of the ring can only be estabUshed by single crystal x-ray diffraction. 

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 course of the photochemically mediated isomerization of vinylazirines is dependent on the stereochemistry of the vinyl group, as is illustrated in Scheme 94a (75JA4682). Under thermal conditions the isomerization proceeds through formation of the butadienylnitrene and subsequent pyrrole formation. Analogous conversions of azirines to indoles have also been effected (Scheme 94b). It is possible that some of the vinyl azide cyclizations discussed in Section 3.03.2.1 proceed via the azirine indeed, such an intermediate has been observed... 

Nitrile ylides derived from the photolysis of 1-azirines have also been found to undergo a novel intramolecular 1,1-cycloaddition reaction (75JA3862). Irradiation of (65) gave a 1 1 mixture of azabicyclohexenes (67) and (68). On further irradiation (67) was quantitatively isomerized to (68). Photolysis of (65) in the presence of excess dimethyl acetylenedicar-boxylate resulted in the 1,3-dipolar trapping of the normal nitrile ylide. Under these conditions, the formation of azabicyclohexenes (67) and (68) was entirely suppressed. The photoreaction of the closely related methyl-substituted azirine (65b) gave azabicyclohexene (68b) as the primary photoproduct. The formation of the thermodynamically less favored endo isomer, i.e. (68b), corresponds to a complete inversion of stereochemistry about the TT-system in the cycloaddition process. 

The formation of g-alkyl-a,g-unsaturated esters by reaction of lithium dialkylcuprates or Grignard reagents in the presence of copper(I) iodide, with g-phenylthio-, > g-acetoxy-g-chloro-, and g-phosphoryloxy-a,g-unsaturated esters has been reported. The principal advantage of the enol phosphate method is the ease and efficiency with which these compounds may be prepared from g-keto esters. A wide variety of cyclic and acyclic g-alkyl-a,g-unsaturated esters has been synthesized from the corresponding g-keto esters. However, the method is limited to primary dialkylcuprates. Acyclic g-keto esters afford (Zl-enol phosphates which undergo stereoselective substitution with lithium dialkylcuprates with predominant retention of stereochemistry (usually > 85-98i )). It is essential that the cuprate coupling reaction of the acyclic enol phosphates be carried out at lower temperatures (-47 to -9a°C) to achieve high stereoselectivity. When combined with they-... 

Up to this point, we have emphasized the stereochemical properties of molecules as objects, without concern for processes which affect the molecular shape. The term dynamic stereochemistry applies to die topology of processes which effect a structural change. The cases that are most important in organic chemistry are chemical reactions, conformational changes, and noncovalent complex formation. In order to understand the stereochemical aspects of a dynamic process, it is essential not only that the stereochemical relationship between starting and product states be established, but also that the spatial features of proposed intermediates and transition states must account for the observed stereochemical transformations. 

The addition of methylmagnesium iodide to 2-phenylpropanal is stereoselective in producing twice as much syn-3-phenyl-2-butanol as the anti isomer (entry 5). The stereoselective formation of a particular configuration at a new stereogenic center in a reaction of a chiral reactant is called asymmetric induction. This particular case is one in which the stereochemistry can be predicted on the basis of an empirical correlation called Cram s rule. The structural and mechanistic basis of Cramls rule will be discussed in Chapter 3. 

A significant modification in the stereochemistry is observed when the double bond is conjugated with a group that can stabilize a carbocation intermediate. Most of the specific cases involve an aryl substituent. Examples of alkenes that give primarily syn addition are Z- and -l-phenylpropene, Z- and - -<-butylstyrene, l-phenyl-4-/-butylcyclohex-ene, and indene. The mechanism proposed for these additions features an ion pair as the key intermediate. Because of the greater stability of the carbocations in these molecules, concerted attack by halide ion is not required for complete carbon-hydrogen bond formation. If the ion pair formed by alkene protonation collapses to product faster than reorientation takes place, the result will be syn addition, since the proton and halide ion are initially on the same side of the molecule. 

There are several general classes of pericyclic reactions for which orbital symmetry factors determine both the stereochemistry and relative reactivity. The first class that we will consider are electrocyclic reactions. An electrocyclic reaction is defined as the formation of a single bond between the ends of a linear conjugated system of n electrons and the reverse process. An example is the thermal ring opening of cyclobutenes to butadienes ... 

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