Steric-approach control

More bulky nucleophiles usually approach the cyclohexanone carbonyl from the equatorial direction. This is called steric approach control and is the result of van der Waals type repulsions. Larger nucleophiles encounter the 3,5-axial hydrogens on the axial approach trajectory. 

Dibenzylamino)-3-phenylpropanal adds benzyllithium reagents with virtually complete steric approach controlled selectivity again the simple diastereoselectivity is poor (approx. 1 11 2)5. 

Substrate control by a chiral aldehyde addition with steric approach control ... 

The diastereofacial selectivity of addition of achiral allylchromium to chiral aldehydes is mainly determined by steric approach control even a- and /5-alkoxy-subsliluents apparently do not give rise to a rate-determining chelation9. 

Scheme 2.2 illustrates several examples of the Mukaiyama aldol reaction. Entries 1 to 3 are cases of addition reactions with silyl enol ethers as the nucleophile and TiCl4 as the Lewis acid. Entry 2 demonstrates steric approach control with respect to the silyl enol ether, but in this case the relative configuration of the hydroxyl group was not assigned. Entry 4 shows a fully substituted silyl enol ether. The favored product places the larger C(2) substituent syn to the hydroxy group. Entry 5 uses a silyl ketene thioacetal. This reaction proceeds through an open TS and favors the anti product. 

Scheme 4.1 includes examples of oxymercuration reactions. Entries 1 and 2 illustrate the Markovnikov orientation under typical reaction conditions. The high exo selectivity in Entry 3 is consistent with steric approach control on a weakly bridged (or open) mercurinium ion. There is no rearrangement, indicating that the intermediate is a localized cation. 

For reduction of monofunctional ketones, the most effective catalysts include diamine ligands. The diamine catalysts exhibit strong selectivity for carbonyl groups over carbon-carbon double and triple bonds. These catalysts have a preference for equatorial approach in the reduction of cyclohexanones and for steric approach control in the reduction of acyclic ketones.51... 

When a ketone is relatively hindered, as, for example, in the bicyclo[2.2. l]heptan-2-one system, steric approach control governs stereoselectivity even for small hydride donors. 

Entry 5 is an example of the use of fra-(trimethylsilyl)silane as the chain carrier. Entries 6 to 11 show additions of radicals from organomercury reagents to substituted alkenes. In general, the stereochemistry of these reactions is determined by reactant conformation and steric approach control. In Entry 9, for example, addition is from the exo face of the norbornyl ring. Entry 12 is an example of addition of an acyl radical from a selenide. These reactions are subject to competition from decarbonylation, but the relatively slow decarbonylation of aroyl radicals (see Part A, Table 11.3) favors addition in this case. 

The anti stereospecificity of epoxidation by the peracid is interpreted as due to association of the reagent with the allylic hydroxyl group which directs the entering oxygen atom to the same face of the molecule. The stereospecificity of bromohydrin formation is explicable in terms of steric approach control involving initial attack of the bulky bromine atom on the face opposite to the benzylic hydroxyl group (7). 

Hydrides and complex hydrides tend to approach the molecule of a compound to be reduced from the less hindered side steric approach control). If a relatively uninhibited function is reduced the final stereochemistry is determined by the stability of the product (product development control). In addition, torsional strain in the transition state affects the steric outcomes of the reduction. 

DIASTEREOMERS STEREOSELECTIVITY STEREOSPECIFICITY STERIC-APPROACH CONTROL STERIC HINDRANCE Steric hindrance effect on ligand binding, SCATCHARD RLOT Stern layer,... 

A large amount of data has been accumulated on the stereoselectivity of reduction of cyclic ketones.81 Table 5.4 compares the stereochemistry of reduction of several ketones by hydride donors of increasing seric bulk. The trends in the table illustrate the increasing importance of steric approach control as both the hydride reagent and the ketone become more highly substituted. The alkyl-substituted borohydrides have especially high selectivity for the least hindered direction of approach. 

Obgleich der Literatur keine klare stereo-chemische Deutung dieser Prozesse zu entnehmen ist, scheint ein einfaches Modell mit steric approach control" eine einheit-liche Interpretation zu erlauben. Akzep-tiert man II als die stabilste Konformation der Azomethine , so wird deutlich, daB... 

Bei anderen acyclischen, mono- und bicyclischen cis-Olefinen lag p zwi-schen 48 und 91 %. Klassifiziert man in VII die Substituenten der am Bor haftenden asymmetrischen C-Atome als L, M und S, so ergeben sich fiir den spezifitatsbestimmenden Schritt unter der Annahme einer steric approach control" die cyclischen Qbergangszustande VIII und IX, von denen VIII in Ubereinstimmung mit den Expcrimenten begunstigt ist. 

This unusual cis addition, which violates the steric approach control rule , seems to be solely related to the benzyl group31 as inducer of the configuration of the newly formed stereogenic center. 

Steric approach control, 67 Steric strains, 71 Steric strain control, 69 Steroid hydrogenation, 111 5/3-Stigmast-22-en-3-one, 130 Stigmasterol, 266 Sulfur dichloride, 459 Sulfur tetrafluoride, 459, 472 Sulfur tetrafluoride fluorination, 471 Surface catalysts, 157... 

Elaboration of 2-isoxazolines via their 4-endo-anions has been studied as a method to synthesize y-amino alcohols (78TL3129,3133,81AG(E)601,603). When the 5-methyl-3-phenyl-2-isoxazoline (527) was deprotonated with LDA/HMPA and methylated with methyl iodide, the tra 5-4,5-substituted isoxazoline (528) was formed predominantly (trans-.cis = 12 1). Reduction of this isoxazoline with lithium aluminum hydride proceeded with steric approach control to provide a diastereomeric mixture of y-amino alcohols (529, 530 Scheme 116). The 5-substituent was found to exhibit a greater steric influence on this reaction than the 4-substituent. 

The course of the reaction of furan and DMAD is temperature dependent (73CJC4125). The initially formed monoadduct (118) acts as a dienophile and further addition of furan can occur at the di- or tetra-substituted double bonds. In such additions to norbornene-type dienophiles the diene is subject to steric approach control and approach to the exo face is preferred. At 25 °C the tetrasubstituted double bond acts as a dienophile and the endo,exo... 

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