Equatorial alkyl halides

The equatorial orientation of the newly introduced alkyl group may be controlled in both (3) and (6) by stereoelectronic and steric factors. The attack of the enolate anions (2) and (5) by the alkyl halide proceeds in a plane that is perpendicular to the plane of the enolate system. Products result from attack at the less hindered a- or -face, respectively... 

Addition of Bu3SnLi or McsSnI.i to 4-t-butylcyclohexanone affords mixtures of trans and cis adducts in ratios that depend on reaction conditions (Table ll)68. In THF, a 93 7 mixture is obtained with both reagents. This ratio is thought to represent the thermodynamic distribution—the axial stannane being favored. In ether, the cis isomer predominates, suggesting a kinetic preference for equatorial addition. Each of the two isomers can be lithiated with BuLi. Subsequent treatment with alkyl halides or carbonyl compounds affords the substituted alkoxy cyclohexanes with retention of stereochemistry. 

Alcohols, conversion to alkyl halides with triphcnylphosphine-halogen adducts, 48, 53 synthesis of equatorial, 47, 19 Aldehydes, aromatic, synthesis of, 47, 1... 

Even though we define the atropisomerism as above for present purposes, there remain some ambiguities. sym-Tetrabromoethane was obtained in different modifications according to the method of crystallization at low temperature (13). These were found by spectroscopy to correspond to retainers. Similar situations occur in other alkyl halides and acetates (14,15). Such cases will not be included in the discussion, mainly because crystalline atropisomers are isolated at far lower temperatures than die ambient, and their barriers to rotation have not been determined by equilibration. Also excluded is the isolation of chlorocyclohexane (16). The isolation of the equatorial and axial conformational isomers was possible only by crystallization of the former at - 150°C, although it was possible to observe equilibration between the equatorial and the axial forms at higher temperatures. 

The alkyl halide is tertiary and so undergoes hydrolysis by an SN1 mechanism. The carbocation can be captured by water at either face. A mixture of the axial and the equatorial alcohols is formed. 

C-(w-propyl)-N-phenylnitrone to N-phenylmaleimide, 46, 96 semicarbazide hydrochloride to ami-noacetone hydrochloride, 45,1 tetraphenylcyclopentadienone to diphenyl acetylene, 46, 44 Alcohols, synthesis of equatorial, 47, 19 Aldehydes, aromatic, synthesis of, 47,1 /8-chloro-og3-unsaturated, from ketones and dimethylformamide-phosphorus oxychloride, 46, 20 from alkyl halides, 47, 97 from oxidation of alcohols with dimethyl sulfoxide, dicyclohexyl carbodiimide, and pyridinium trifluoroacetate, 47, 27 Alkylation, of 2-carbomethoxycyclo-pentanone with benzyl chloride, 45, 7... 

Beckett and coworkers [5-7] found that quatemization of 4 with alkyl halides reversed the conformational equilibrium even further and, for a system like 6, the conformer 6a with the C5-substituent occupying the equatorial position predominated. Obviously, the A(1 2) strain present in 6a is less than the steric strain arising from 1,3-diaxial interaction between the ethyl and methyl substituents in the conformer 6b. 

One of the earliest examples of a carcerand was prepared by joining two hemispherical bowl-shaped components together (cavitands, such as calix[4]arenes or the closely related [4]resorcarenes (Section 2.7.2). This was achieved by reacting a thiol-appended resorcarene with an analogous alkyl halide to form a thioether-bridged equatorial seam (2.123). This led to a challenging analysis as carcerand... 

In tertiary compounds in which rotation can occur about two or three axes, up to ten rotamers are theoretically possible but usually steric factors limit the numbers to two or three. The frequency of the THHH form is at 560 cm" and that of the TCHH at 620 cm". In cyclic structures, such as cyc/ohexanes, chlorine substitution can be either axial or equatorial, and the two configurations show different frequencies as before. The connection between these cases and the simple alkyl halides has been discussed by Sheppard [17, 28]. In cyc/ohexane the C—Cl absorptions are at 742 cm" (equatorial) and 688 cm" (axial) [15], and similar results are shown by halogenated steroids. In the latter case, however, there are also some differences which are characteristic of... 

TMSLi adds to cyclohexenone in THF-HMPA to give exclusively the 1,4-addition product (eq 3). The intermediate enolate may be stereoselectively alkylated at carbon with alkyl halides, or 0-silylated with chlorotrimethylsilane to provide the enol ether. Nucleophilic 1,4-addition to cyclohexenones is quite stereoselective. Reaction of 5-methylcyclohex-2-enone with TMSLi occurs predominantly by axial attack, resulting in a 92 8 ratio of axial to equatorial products. TMSLi also undergoes diastereoselec-tive nucleophilic addition to 1-naphthyloxazolines (eq 4) however, the addition of the silyl nucleophile is not as selective as the... 

The reaction of dibutyltin oxide with pyranoid m-l,2-diols has attracted interest, since the resulting cyclic dibutylstannylene derivatives are substituted regioselectively at the equatorial oxygen-atom when treated with an acyl chloride or an active alkyl halide. Thus the cyclic dibutylstannylene derivative (332 ... 

The j -BuLi-(—)-sparteine combination is widely used in enan-tioinductive organic reactions. 4.H7-i22 Benzylic asymmetric alkylation may thus be achieved by subsequent treatment with alkyl halides, alkyl tosylates, and allyl tosylates 1,3-Oxathiane derivatives shown in eq 50 may be lithiated and quenched with electrophiles. An interesting aspect of this reaction is the equatorial stereoselectivity, which is independent of the size of the electrophile introduced. ... 

Five-membered cyclic dibutylstannylene acetals formed on vicinal cw-axial-equatorial pairs of hydroxyl groups selectively enhance the nucleophilicity of the equatorial oxygen in 0-alkylation reactions [179, 180], On the basis of this rule Schuerch surmised that alkylation of the tin complex 103, having the anomeric oxygen locked in the equatorial position, should lead to P-mannosides [181]. This assumption was proved by treating the mannose diol 102 with Bu2SnO (—> 103) followed by in situ exposure to alkyl halides whereby P-mannopyranosides 104 were formed stereospecifically (Scheme 30) [181],... 

Schrauzer and co-workers have studied the kinetics of alkylation of Co(I) complexes by organic halides (RX) and have examined the effect of changing R, X, the equatorial, and axial ligands 148, 147). Some of their rate constants are given in Table II. They show that the rates vary with X in the order Cl < Br < I and with R in the order methyl > other primary alkyls > secondary alkyls. Moreover, the rate can be enhanced by substituents such as Ph, CN, and OMe. tert-Butyl chloride will also react slowly with [Co (DMG)2py] to give isobutylene and the Co(II) complex, presumably via the intermediate formation of the unstable (ert-butyl complex. In the case of Co(I) cobalamin, the Co(II) complex is formed in the reaction with isopropyl iodide as well as tert-butyl chloride. Solvent has only a slight effect on the rate, e.g., the rate of reaction of Co(I) cobalamin... 

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