Problems Stereochemistry

Strategy Problem 7 Synthesis of a single enantiomer. Many compounds such as pharmaceuticals, flavourings, and insect control chemicals must not only have the right relative stereochemistry but must be optically active too if tliey are to be of any use. Consider the strategy of synthesising one enantiomer ... 

General problems with synthetic organic reactions are discussed together with some practical solutions for specific examples. These problems include 9 regio- and stereoselectivity by exploitation of the substrates stereochemistry (e.g., p. 20ff.) and differentiated nucleophilicity (p. 24f, 44f, 56ff.)... 

As you work with Fischer projections you may notice that some routine structural changes lead to predictable outcomes—outcomes that may reduce the number of manip ulations you need to do to solve stereochemistry problems Instead of listing these short cuts Problem 7 10 invites you to discover some of them for yourself... 

Expand your answer to Problem 27 10 by showing the struc tural formula for each dipeptide m a manner that reveals the stereochemistry at the a carbon atom... 

Among the modem procedures utilized to estabUsh the chemical stmcture of a molecule, nuclear magnetic resonance (nmr) is the most widely used technique. Mass spectrometry is distinguished by its abiUty to determine molecular formulas on minute amounts, but provides no information on stereochemistry. The third most important technique is x-ray diffraction crystallography, used to estabUsh the relative and absolute configuration of any molecule that forms suitable crystals. Other physical techniques, although useful, provide less information on stmctural problems. 

When topological strategies are used concurrently with other types of strategic guidance several benefits may result including (1) reduction of the time required to find excellent solutions (2) discovery of especially short or convergent synthetic routes (3) effective control of stereochemistry (4) orientational (regiochemical) selectivity (5) minimization of reactivity problems and (6) facilitation of crucial chemical steps. 

The data available on the stereochemistry of reduction of steroidal ketones have been obtained largely in the course of synthetic work, rather than in studies devoted specifically to stereochemical problems. As discussed in an earlier section, the proportion of epimers depends on the steric environment of the ketone, the reagent, the solvent and the temperature. These factors will be discussed below. 

Polypropylene made by free-radical polymerization is generally atactic , that is to say, there is no pattern to the stereochemistry. On the other hand, both isotactic polypropylene (in which all the stereocenters are the same) and syndiotactic polypropylene (in which the stereocenters alternate) may be made via the Ziegler-Natta process (see Chapter 18, Problem 4). Experimentally, both isotactic and syndiotactic polypropylene generally have higher melting points than atactic polypropylene. 

In one of their solutions to the problem, Corey and his coworkers solved the first problem by starting with a preconstructed cyclopentane the stereochemistry was steered by deriving the oxygen atoms from a rigid bicyclic molecule. Alkylation of... 

Aromatic rings can be reduced without difficulty. Major problems connected with these reductions concern maintenence of other functions, control of regioselectivity in polycyclic aromatics, and control of stereochemistry. 

Other methods of identification include the customary preparation of derivatives, comparisons with authentic substances whenever possible, and periodate oxidation. Lately, the application of nuclear magnetic resonance spectroscopy has provided an elegant approach to the elucidation of structures and stereochemistry of various deoxy sugars (18). Microcell techniques can provide a spectrum on 5-6 mg. of sample. The practicing chemist is frequently confronted with the problem of having on hand a few milligrams of a product whose structure is unknown. It is especially in such instances that a full appreciation of the functions of mass spectrometry can be developed. 

Problem 7.3 What product would you expect to obtain from addition of Cl2 to 1,2-dimethyl-cyclohexene Show the stereochemistry of the product. 

Problem 7.4 Addition of 11C1 to 1,2-dimethylcycJohexene yields a mixture of two products. Show the stereochemistry of each, and explain why a mixture is formed. 

Problem 7.5 What product would you expect from the reaction of cyclopentene with NBS and water Show the stereochemistry. 

Problem 9.25 Lactic acid buildup in tired muscles results from reduction of pyruvate. If the reaction occurs from the Re face, what is the stereochemistry of the product ... 

Problem 9.26 The aconitase-catalyzed addition of water to ds-aconitate in the citric acid cycle occurs with the following stereochemistry. Does the addition of the OH group occur on the Re or the Si face of the substrate What about the addition of the H Does the reaction have syn or anti stereochemistry ... 

Problem 11.8 What product(s) would you expect from reaction of (S)-3-chloro-3-methyloctanc with acetic acid Show the stereochemistry of both reactant and product. 

Show the stereochemistry of the epoxide (see Problem 11.42) you would obtain by formation of a bromohydrin from frnm-2-butene, followed by treatment with base. 

Dimethyl butynedioate also undergoes a Diels-Alder reaction with (2 ,4Z)-hexadiene, but the stereochemistry of the product is different from that of the (2 ,4 ) isomer (Problem 14.55). Explain. 

What is the stereochemistry of the product from acid-catalyzed hydrolysis of t/wrs-S,6-epoxydecane How does the product differ from that formed in Problem 18.33 ... 

Problem 19.19 What is the stereochemistry of the pyruvate reduction shown in Figure 19.15 Does NADH lose its pro-R or pro-S hydrogen Does addition occur to the Si face or Re face 1 of pyruvate ... 

Problem 25.2 Convert the following Fischer projections into tetrahedral representations, and, assign R or S stereochemistry to each ... 

Draw the three-dimensional furanose form of ascorbic acid (Problem 25.32), and assign R or S stereochemistry to each chirality center. 

Problem 30.7 i Classify the following sigmatropic reaction by order Ja J J, and tell whether it will proceed with suprafacial or antarafacial stereochemistry ... 

Photolysis of the c/.wcyclobufene isomer in Problem 30.25 yields c/s-cyclo-dodecaen-7-yne, but photolysis of the trans isomer yields frm/s-cyclododecaen-7-yne. Explain these results, and identify the type and stereochemistry of the pericyclic reaction. 

In 1952, it was reported that a constituent of excretions from female American cockroaches of the species Periplaneta ameri-cana is an extraordinarily potent sex pheromone.1 Early attempts to isolate and characterize the active compounds were hampered because individual cockroaches store only minute amounts of the pheromone ( 1 pg), and a full 25 years elapsed before Persoons et al. reported the isolation of two extremely active compounds, periplanones A and B.2 The latter substance is present in larger relative measure and its germacranoid structure (1, without stereochemistry) was tentatively assigned on the basis of spectroscopic data. Thus, in 1976, the constitution of periplanone B was known but there remained a stereochemical problem of a rather serious nature. Roughly three years intervened between the report of the gross structure of periplanone B and the first total synthesis of this substance by W. C. Still at Columbia.3... 

It is worth pointing out that the stereochemistry of intermediate 147 at C-9 and C-10 is inconsequential since both positions will eventually bear trigonal carbonyl groups in the final product. The synthetic problem is thus significantly simplified by virtue of the fact that any or all C9-C10 diol stereoisomers could be utilized. A particularly attractive means for the construction of the C9-C10 bond and the requisite C8-C10 functionality in 147 is revealed by the disconnection shown in Scheme 41. It was anticipated that the venerable intermolecular aldol reaction could be relied upon to accomplish the union of aldehyde 150 and methyl glycolate (151) through a bond between carbons 9 and 10. 

A valuable feature of the Nin/Crn-mediated Nozaki-Takai-Hiyama-Kishi coupling of vinyl iodides and aldehydes is that the stereochemistry of the vinyl iodide partner is reflected in the allylic alcohol coupling product, at least when disubstituted or trans tri-substituted vinyl iodides are employed.68 It is, therefore, imperative that the trans vinyl iodide stereochemistry in 159 be rigorously defined. Of the various ways in which this objective could be achieved, a regioselective syn addition of the Zr-H bond of Schwartz s reagent (Cp2ZrHCl) to the alkyne function in 165, followed by exposure of the resulting vinylzirconium species to iodine, seemed to constitute a distinctly direct solution to this important problem. Alkyne 165 could conceivably be derived in short order from compound 166, the projected product of an asymmetric crotylboration of achiral aldehyde 168. 

A detailed discussion of the different acidities of the diastereotopic a-methylene protons in sulphoxides, as well as of the stereochemistry of reactions of sulphoxide a-carbanions with electrophilic reagents is beyond the scope of this chapter. A recent review by Wolfe pertinent to these problems is available392. 

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