Stereochemistry of products

Enantiomerically pure 3-tolyl-2-sulfinyl-2-cyclopentenone 37 undergoes smooth, mild and diastereoselective conjugate hydride addition with lithium tri(sec-butyl)borohydride to afford ultimately 3-tolylcyclopentanone 38 in 93% enantiomeric purity (equation 35)78. The absolute stereochemistry of product 38 is consistent with a chelated intermediate directing hydride addition from that diastereoface containing the sulfoxide lone pair. 

The mechanism for the reaction catalyzed by cationic palladium complexes (Scheme 24) differs from that proposed for early transition metal complexes, as well as from that suggested for the reaction shown in Eq. 17. For this catalyst system, the alkene substrate inserts into a Pd - Si bond a rather than a Pd-H bond [63]. Hydrosilylation of methylpalladium complex 100 then provides methane and palladium silyl species 112 (Scheme 24). Complex 112 coordinates to and inserts into the least substituted olefin regioselectively and irreversibly to provide 113 after coordination of the second alkene. Insertion into the second alkene through a boat-like transition state leads to trans cyclopentane 114, and o-bond metathesis (or oxidative addition/reductive elimination) leads to the observed trans stereochemistry of product 101a with regeneration of 112 [69]. 

The stereochemistry of products 27 (Table 6, entries 2, 3, and 4) can be explained distinctly on the same basis that alkyl substituents R1, R2 are positioned in quasi equatorial positions in the transition structure. Exclusive formation of the all-cis isomer in the reaction of cyclohexyl acetate (entry 5) is further evidence to support the oxido-carbene interaction in a double-chaired bicyclic structure 28, as depicted in Scheme 13, Eq. 1. 

SCHEME 4. Possible stereochemistries of products from reactions proceeding via substituted aUyl Grignard intermediates... 

The mechanism of epoxidation has been studied in detail both with P450 enzymes [68] and synthetic metal porphyrins [69], The problem finding a conclusive answer on how the enzymatic reaction proceeds is due to the fact that intermediates have not been detected but inferred by investigating the stereochemistry of product formation. By and large it is safe to say that the reaction depends on the steric hindrance imposed by the olefin s substitutents, the electron donating character of the olefin, and the electron demand of the oxo-iron(IV) porphyrin used. In particular the last aspect makes it difficult to draw conclusions from reactions with model compounds, since these metal porphyrins behave quite differently from native P450 due to the distinct electronic nature of both the metal and the porphyrin. 

An interesting example of the apparent dependence of stereoselectivity on the rate of breakdown of the initial cyclization intermediate has been observed in cyclizations with isoxazolines as the nucleophilic functionality (equation 48 and Table 14).141 The stereochemistry of products from cyclizations to form tetrahydrofuran products varies significantly upon changing the 3-substituent of the isoxazoline ring (Table 14, entries 1-3). The exact factors controlling these variations have not been determined, but the stereoselectivity may be synthetically useful. Particularly noteworthy is the high selectivity for the less... 

Here again, comparison of the stereochemistries of product and starling material provides insight into the course of the reaction. 

Reaction of the carbohydrate-based cyclic sulfites with NaSCN was used for the synthesis of f -l, 2-liised oxazolidine-2-thiones (Table 4) <1995TL5347>. Seleno and oxo derivatives were obtained with KSeCN or NaOCN, respectively <2000MI397>. The stereochemistry of products can be explained by the intermediate isomerization of /3-thiocyanates into cr-isothiocyanates (Scheme 10) <1995TL5347, 2000MI397>. 

Methyl radicals are essentially planar but ESR measurements [116], supported by theoretical calculations [114], show that fluoromethyl radicals deviate from planarity to increasingly pyramidal structures upon further fluorination, with CF3 measured to be 49.1° from planarity. The barriers to inversion of fluoromethyl radicals increase in the order CFH2 < CF2H < CF, while fluorocyclopropyl radicals (Figure 4.46) adopt a fixed pyramidal conformation at the radical centre [117], as determined by ESR at — 108°C. The tendency for fluorine to induce pyrimidalisation of radical centres has also been used to account for the stereochemistry of products [118]. 

Problem 9.26 Draw the organic products formed in each reaction, and indicate the stereochemistry of products that contain stereogenic centers. 

In this case, nucleophilic attack of OCH3 occurs from the back side at either C-O bond, because both ends are equally substituted. Because attack at either side occurs with equal probability, an equal amount of the two enantiomers is formed—a racemic mixture. This is a specific example of a general rule concerning the stereochemistry of products obtained from an achiral reactant. 

It is important in a mechanistic discussion of stereochemical results to know whether the stereochemistry of products is kinetically or thermodynamically controlled. However, in many reports this point is ignored moreover, only a few reports have mentioned the thermodynamic equilibrium ratio of stereoisomeric products. The former point can be examined not only by experiment but also by computational molecular calculation, but it may not always be easy to determine the ratio. For the latter, much more attention to the stereochemical hterature must be paid by electrochemists engaging in stereochemical studies. 

Baizer and coworkers established the most brilliant industrial electroorganic synthesis of the hydrodimerization of acrylonitrile to adiponitrile. They extended this hydrodimerization to a variety of activated olefins and in some cases [41 3] paid attention to the stereochemistry of products. However, their stereochemical data were not enough to discuss the stereochemical course of the reaction. Afterward, an attempt was made to provide a working hypothesis in the hydrodimerization of cinnamates by considering an orientated adsorption of radical anion intermediates on a cathode surface, but this was not persuasive because of a lack of experimental data on the stereochemistry of both the starting olefins and products. Recently Utley and coworkers [44-46] have reported stereochemical data of hydrodimers derived from a variety of cinnamic acid esters with chiral alcohol components. 

Iverson and Madsen [193] reported a synthetically interesting electroreductive ringopening reaction of cyclic quaternary ammonium salts. The stereochemistry of products is greatly affected by pH ... 

Insertion stereochemistries for the alkyne insertion process were found to be variable. Sometimes cis addition of the Ni-CHs bond occurred (e.g., for PhCsCCHs), sometimes trans addition occurred (e.g., for PhC=CPh), and sometimes a mixture of isomers was obtained. Allowing the complexes to stand led to a thermodynamically controlled mixture of cis and trans insertion products. Equilibration of cis and trans vinylaluminum compounds is known. Initial cis insertion of the alkyne yields a coor-dinately unsaturated vinylnickel intermediate that accounts for the different stereochemistry of products formed under kinetic control. Isomerization of the double bond occurs for this intermediate in competition with product formation. Thus the stereochemistry of the kinetic product does not necessarily give the stereochemistry of a preceding insertion step. 

The stereochemistry of product formation is consistent with an intermediate trisho-mocyclopropenium ion (563). Whereas a p-anisyl group in the 7-position of (395) is capable of swamping the tt-participation by the double bond, it does not entirely eliminate 7r a-participation (557b) hydrolyzes 4000 times faster than the 7-norbom-yl analog to give (5646)242. ... 

The stereochemistry of products relative to starting materials can give important clues to the structure of the transition state. The stereochemistry of molecules gives rise to two types of isomerism optical isomerism (cnantiomcrismjand geometrical isomerism. 

Table II. Yield (Percent) and Stereochemistry of Products of Solvolyses of Cyclohexen-4-yl Tosylate (III) in Solvents of Various Nucleophilicity and Ionizing Power...

Porter N.A., WeberB.A., Weenen FI. and Khan J. A. (1980) Autoxidation of polyunsaturated lipids factors controlling the stereochemistry of product hydroperoxides. J. Am. Chem. Soc., 102, 5597-5601. 

The presence of a chiral auxiliary can influence the stereochemistry of products formed in a Mukaiyama reaction. A stereogenic center derived from a chiral amino alcohol was incorporated in the enol ether moiety (see 445). When this reacted with benzaldehyde and TiCU. the alcoholate products were 446 and 447 (R = the chiral auxiliary) The diastereoselectivity in this reaction was quite good (95 5 favoring 446) and each product was formed with high enantioselectivity.246 It is also possible to incorporate the stereogenic center into the starting material (a chiral template, as discussed in sec. 10.9).247... 

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