Stereochemical integrity

Enolization of an aldose or a ketose gives an enediol Enediols can revert to aldoses or ketoses with loss of stereochemical integrity at the a carbon atom... 

Original Synthesis. The first attempted synthesis of i7-biotin in 1945 afforded racemic biotin (Fig. I). In this synthetic pathway, L-cysteine [52-90-4] (2) was converted to the methyl ester [5472-74-2] (3). An intramolecular Dieckmaim condensation, during which stereochemical integrity was lost, was followed by decarboxylation to afford the thiophanone [57752-72-4] (4). Aldol condensation of the thiophanone with the aldehyde ester [6026-86-4]... 

If the a-carbon atom of an aldehyde or a ketone is a chuality center, its stereochemical integrity is lost on enolization. Enolization of optically active sec-butyl phenyl ketone leads to its racemization by way of the achiral enol fonn. 

Zincke-type salts derived from other aromatic nitrogen heterocycles also undergo Zincke reactions. The isoquinolinium salt 6 (Scheme 8.4.16) permitted incorporation of a phenyl ethylamine chiral auxiliary, providing salt 48. In this context and others (vide infra), Marazano and co-workers found that refluxing -butanol was a superior solvent system for the Zincke process. Additionally, the stereochemical integrity of the or-chiral amino fragment was reliably maintained. 

Methods of assessing the stereochemical integrity of enantiomeric drug substances and drug products should be included in the stability protocols for both, but stereoselective tests may not be required once it has been shown that racemization does not occur. 

Most radicals located on saturated bonds are jt-radicals with a planar configuration and may be depicted with the free spin located in a p-orbital (1). Because such radical centers are achiral, stereochemical integrity is lost during radical formation, A new configuration will be assumed (or a previous configuration resumed) only upon reaction. Stereoselectivity in radical reactions is therefore dependent on the environment and on remote substituents. 

Photochemical reactions of carbonyl compounds with alkenes give the oxetanes (Scheme 30). The stereochanical course depends on the substituents of the alkenes [16]. The reactions proceed with the retention of the configuration of the alkenes for the electron accepting substituent, e.g., CN. The stereochemical integrity is lost for the donating group, e.g., OCH. ... 

Thermal dimerization of ethylene to cyclobutane is forbidden by orbital symmetry (Sect 3.5 in Chapter Elements of a Chemical Orbital Theory by Inagaki in this volume). The activation barrier is high E =44 kcal mof ) [9]. Cyclobutane cannot be prepared on a preparative scale by the dimerization of ethylenes despite a favorable reaction enthalpy (AH = -19 kcal mol" ). Thermal reactions between alkenes usually proceed via diradical intermediates [10-12]. The process of the diradical formation is the most favored by the HOMO-LUMO interaction (Scheme 25b in chapter Elements of a Chemical Orbital Theory ). The intervention of the diradical intermediates impfies loss of stereochemical integrity. This is a characteric feature of the thermal reactions between alkenes in the delocalization band of the mechanistic spectrum. 

A stronger donor, the butadiene with the amino groups in place of the methoxy group in the 1,4-positions, was calculated to react with TCNE via a zwitterion (pseudoexcitation band in Scheme 7) [34], The loss of the stereochemical integrity was observed inthe[4+2]cycloadditionreactionsbetweensomestrongdonors,l,4-bis(dimethylamino) butadienes, and acceptors, fumaric and maleic dinitriles [36],... 

The boron enolates derived from (5)-4-silylated 2,2-dimethyl-l,3-dioxan-5-one undergo anti diastereoselective aldol reactions which provide access to protected oxopolyols of high stereochemical integrity <96SYN1095>. 

We discovered a complementary procedure for conversion of OMen to other functional groups. The ester P-OMen bond was shown to be cleaved in a stereoselective manner reductively [85,86]. The cleavage takes place with almost complete preservation of stereochemical integrity at phosphorus. The reducing agents are usually sodium or Hthium naphthalenide, lithium biphenyUde, and Hthium 4,4 -di-fert-butylbiphenyl (LDBB). The species produced is then quenched with an alkyl hahde or methanol to afford tertiary or secondary phosphines, respectively (Scheme 5b). Overall, the displacement reaction proceeds with retention of configuration. 

In a variation of these reactions, Grieco and Masaki used p-toluenesulfonyl groups to direct alkylation reactions in the formation of carbon chains and then cleaved the sulphones with lithium in ethylamine. This type of synthetic construction involving the use of sulphur-containing molecules has become a typical sequence in organic syntheses. In this case, the reactions formed part of successful syntheses of squalene and sesquifenchene and were carried out without any migration or loss of stereochemical integrity of the double bonds. Similar sequences have been reported by Trost (prenylation reactions) and Marshall (synthesis of a cembranoid precursor). 

Trifluoromethanesulfonates of alkyl and allylic alcohols can be prepared by reaction with trifluoromethanesulfonic anhydride in halogenated solvents in the presence of pyridine.3 Since the preparation of sulfonate esters does not disturb the C—O bond, problems of rearrangement or racemization do not arise in the ester formation step. However, sensitive sulfonate esters, such as allylic systems, may be subject to reversible ionization reactions, so appropriate precautions must be taken to ensure structural and stereochemical integrity. Tertiary alkyl sulfonates are neither as easily prepared nor as stable as those from primary and secondary alcohols. Under the standard preparative conditions, tertiary alcohols are likely to be converted to the corresponding alkene. 

As with organomagnesium reagents, there is usually loss of stereochemical integrity at the site of reaction during the preparation of alkyllithium compounds.25 Alkenyllithium reagents can usually be prepared with retention of configuration of the double bond.26,27... 

In the preparation of the oxocarboxylic acid imidazolides in ref. [49] and [53], as well as in their aminolysis, the stereochemical integrity was maintained. 

Conlin and co-workers have also studied the fragmentation of a siletane (silacyclobutane). In this case, both the E- and Z-isomers of 1,1,2,3-tetra-methylsilane 45 were prepared and thermolyzed (Scheme 8).144 Both E-and Z-isomers of 45 led to the same products in slightly different ratios the major products were propene with silene 46, and E- and Z-2-butenes with silene 47. Silene formation was inferred from detection of the disila-cyclobutane products. During these processes, the stereochemical integrity of the compounds was largely preserved. 

Several studies of the electrochemical reduction of cyclopropyl halides have been reported in the literature 20,26,27,55) t it appears that reduction occurs without complete loss of stereochemical integrity. The predominent stereochemical pattern involves reduction with overall (partial) retention of configuration. The following examples are representative ... 

The large isotope effect suggested that carbon-hydrogen bond cleavage occurs via a linear and symmetrical transition state, while the loss of stereochemical integrity via epimerization suggested the involvement of an intermediate. A mechanism that is consistent... 

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