Configurations stable

Isomeric alkenes may be either constitutional isomers or stereoisomers There is a sizable barrier to rotation about a carbon-carbon double bond which corresponds to the energy required to break the rr component of the double bond Stereoisomeric alkenes are configurationally stable under normal conditions The configurations of stereoisomeric alkenes are described according to two notational systems One system adds the prefix CIS to the name of the alkene when similar substituents are on the same side of the double bond and the prefix trans when they are on opposite sides The other ranks substituents according to a system of rules based on atomic number The prefix Z is used for alkenes that have higher ranked substituents on the same side of the double bond the prefix E is used when higher ranked substituents are on opposite sides... 

The configuration of the amine was retained, except in the case of amino acid derivatives, which racemized at the stage of the pyridinium salt product. Control experiments showed that, while the starting amino acid was configurationally stable under the reaction conditions, the pyridinium salt readily underwent deuterium exchange at the rz-position in D2O. In another early example, optically active amino alcohol 73 and amino acetate 74 provided chiral 1,4-dihydronicotinamide precursors 75 and 76, respectively, upon reaction with Zincke salt 8 (Scheme 8.4.24). The 1,4-dihydro forms of 75 and 76 were used in studies on the asymmetric reduction of rz,>S-unsaturated iminium salts. 

At low tempetatures, a-aLkoxyalkyllitliium reagents ate configurationally stable and tlie resultant aikylcopper or aikylcuprate reagents can transfer tlie ligand witli... 

A similar situation occurs in trivalent phosphorus compounds, or phosphines. It turns out, though, that inversion at phosphorus is substantially slower than Inversion at nitrogen, so stable chiral phosphines can be isolated. (R)- and (5)-metbylpropylphenylphosphine, for example, are configurationally stable for several hours at 100 °C. We ll see the Importance of phosphine chirality in Section 26.7 in connection with the synthesis of chiral amino adds. 

Divalent sulfur compounds are achiral, but trivalent sulfur compounds called sulfonium stilts (R3S+) can be chiral. Like phosphines, sulfonium salts undergo relatively slow inversion, so chiral sulfonium salts are configurationally stable and can be isolated. The best known example is the coenzyme 5-adenosylmethionine, the so-called biological methyl donor, which is involved in many metabolic pathways as a source of CH3 groups. (The S" in the name S-adenosylmethionine stands for sulfur and means that the adeno-syl group is attached to the sulfur atom of methionine.) The molecule has S stereochemistry at sulfur ana is configurationally stable for several days at room temperature. Jts R enantiomer is also known but has no biological activity. 

Molander and Mautner demonstrated that deprotonation of cis-a, 3-epoxysilane 150 with s-BuLi/TMEDA was complete in 10 minutes, whereas the corresponding trows-isomer 150 required 4 hours [56]. Similarly, treatment with butyraldehyde was more efficient with cis-151 (Scheme 5.35), which could also be trapped with a wide variety of other carbonyl-containing electrophiles. The results demonstrated that lithiated epoxides cis- and trons-151 were configurationally stable at -116 °C for periods of up to 4 hours. Only in the case of cis-151 (t-butyl = n-octyl) was the lithiated epoxysilane found to be configurationally unstable. 

Florio et al. demonstrated that the lithiation/electrophile trapping of enantio-pure styrene oxide, as well as the (3-substituted styrene oxides 180 and 182, is totally stereoselective (Scheme 5.42) [66]. These results demonstrate that the intermediate benzylic anions are configurationally stable within the timescale of depro-tonation/electrophile trapping. 

D Chiral or achiral. v/H-carbanions with an additional, configurationally stable stereo-genic center. Very often the additional stereogenic center is in close vicinity (a- or -position) to the anionic center. 

D Achiral non-.s/C-carbanions with a configurationally stable stereogenic center somewhere in the reagent. 

A comparison of the configuration of the substrates and reaction products shows that the oxiranyl anions arc configurationally stable under the reaction conditions. Only one example is known in which isomerization was observed. When the ci.v-tm-butyl-substituted epoxysilane27 was metalated and quenched with 2-cyclohexenone, addition product 27 was obtained under inversion of the anionic center. Presumably the strain created in forcing the ter/-butyl and the trimethylsilyl group cis on the oxirane ring facilitates the isomerization process13. 

Another class of configurationally stable a-mctallo amines is derived from the N-tert-butoxy-carbonyl-protected piperidines 32 and 3516, l7. Addition of the lithiated piperidines to aldehydes leads to mixtures of the anti- and. yin-diastereoiners. Although the diastereoselectivity is low, the diastereomers can be readily separated by chromatography since the. vyn-isomer is often in a cyclized form 34. The stereochemistry of the products obtained from piperidines 32 are consistent with an equatorial a-lithiation followed by addition to the aldehyde with retention of configuration. However, with piperidine 35 selective axial lithiation is observed. 

These results indicate that the a-lithio sulfides are not configurationally stable at —78 C and thus, the high diastereoselectivity reflects the thermodynamic preference of 35 A over 35B3). 

Primary 1-lithio-2-alkenyl diisopropylcarbamates are not configurationally stable in solution. However, under properly selected conditions, the ( )-sparteine complex of the 5-enantiomer crystallizes, leading to a second-order asymmetric transformation6 77-78 132. The suspension is converted to the tri(isopropoxy)titanium derivative with inversion of the configuration, which is shown to have enantiomeric purities up to 94% (Section D.l.3.3.3.8.2.3.). 

Moreover, a-titanated 2-alkenyl carbamates were found to be configurationally stable both with respect to the stereogenic center15 and the double bond16. 

Enantiomerically and diastereomerically enriched lithium-(-)-sparteine complexes of primary 2-alkenylcarbamates, which are configurationally stable as solids (Section 1.3.3.3.1.2.), are transmetalated stereospecifcally by tetraisopropoxytitanium. The resulting titanates are stable in solution and give rise to homoaldol adducts with enantiomeric purities up to 94 % ee107,107a. 

The obtained adducts are not configurationally stable within 24 hours the solid crude product isomerizes to a 31 69 (syn/ami) mixture of diastereomers. 

The stereogenic sulfur atom in sulfoxides is usually configurationally stable at room temperature thus, sulfoxides may be chiral based on this property alone1. In fact, there are many examples of optically active sulfoxides of both synthetic and natural origin. This chapter reviews the important methods for obtaining optically active sulfoxides, and discusses some reactions at sulfur which either leave the coordination number at three or increase it to four, generally with preservation of optical activity. It also describes briefly some recent studies on the conformational analysis and chiroptical properties of sulfoxides. 

The use of a stereogenic carbon centre allowed an efficient asymmetric induction in the benzannulation reaction towards axial-chiral intermediates in the synthesis of configurationally stable ring-C-functionalised derivatives of al-locolchicinoids [51]. The benzannulation of carbene complex 52 with 1-pen-tyne followed by oxidative demetalation afforded a single diastereomer 53 (Scheme 33). 

Chiral compounds are sometimes configurationally stable as solids and configurationally labile in solution. When optically active samples of these deriv-... 

The anomeric configuration is set in the reductive lithiation step, which proceeds via a radical intermediate. Hyperconjugative stabilization favors axial disposition of the intermediate radical, which after another single electron reduction leads to a configurationally stable a-alkoxylithium intermediate. Protonation thus provides the j9-anomer. The authors were unable to determine the stereoselectivity of the alkylation step, due to difficulty with isolation. However, deuterium labeling studies pointed to the intervention of an equatorially disposed a-alkoxylithium 7 (thermodynamically favored due to the reverse anomeric effect) which undergoes alkylation with retention of configuration (Eq. 2). 

Alternative conditions for reductive decyanations can be used. The allylic ether in compound 26, an intermediate in a total synthesis of (-)-roxaticin, was prone to reduction when treated with lithium in liquid ammonia. Addition of the substrate to an excess of lithium di-ferf-butylbiphenylide in THF at -78°C, and protonation of the alkyllithium intermediate provided the reduced product 27 in 63% yield, as a single diastereomer (Eq. 7). a-Alkoxylithium intermediates generated in this manner are configurationally stable at low temperature, and can serve as versatile synthons for carbon-carbon bond forming processes (see Sect. 4). 

This route has been widely exploited because of the availability of a-amino azomethine compoimds from natural (S)-a-amino acids, through the corresponding a-amino aldehydes, which are configurationally stable provided that the amino function is suitably protected. Moreover, some a-amino acids are available with the R configuration and a number of enzymatic and chemical transformations have been described for the preparation of optically active unnatural a-amino acids. Overall, the route suffers from the additional steps required for protection/deprotection of the amino function and, in the case of hydrazones and nitrones, cleavage of the N - N or N - O bond. 

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