cis-1,3-Dimethylcyclobutane has two planes of symmetry.

Atorvastatin is sold under the trade name Lipitor and is used for lowering cholesterol. Annual global sales of this compound exceed $13 billion. Assign a configuration to each chirality center in atorvastatin: N N O H OH OH OH O F

Atropine, extracted from the plant Atropa belladonna, has been used in the treatment of bradycardia (low heart rate) and cardiac arrest. Draw the enantiomer of atropine:NCH3OHOOH

Paclitaxel (marketed under the trade name Taxol) is found in the bark of the Pacific yew tree, Taxus brevifolia, and is used in the treatment of cancer: O N O O O O O OH O OH H O O O O OH H

Classify each of the following compounds below as cis, trans, or not stereoisomeric: OH HO HO

For each of the following pairs of compounds, determine the relationship between the two compounds: (a) (b) O O N CH3 O H O OH (c) Br Br (d) (e) (f) (g) (h) (i) OH OH (j) OH OH (k) Cl Cl Cl Cl (l)

Identify the number of stereoisomers expected for each of the following: (a) OH OH Cl (b) OH OH (c) Me Me Cl (d) (e) HO OH (f)

Draw the enantiomer for each of the following compounds: (a) Cl OH (b) (c) (d) Et OH (e) Cl Me F OH (f) Cl F (g) H OH H OH CH3 HO H O H (h) HO H H CH2OH O OH OH HO H (i) OH OH Cl Me Cl Me OH O (j) OH (k) OH Cl (l) OH

Identify the configuration of each chirality center in the following compounds: (a) Me O Et OH (b) NH2 (c) Cl (d) HO Et Cl (e) O H F (f) Cl Br O H (g) HO (h) H Me OH Me HO H (i) Cl O

You are given a solution containing a pair of enantiomers (A and B). Careful measurements show that the solution contains 98% A and 2% B. What is the ee of this solution?

For each of the following pairs of compounds, determine the relationship between the two compounds: (a) H CH2OH CH2OH OH HO H HO H HO H O H O H (b) H CH2OH CH2OH OH OH O OH O OH H H OH HO H (c) Cl Cl Cl Cl (d) (e)

For each of the following pairs of compounds, determine the relationship between the two compounds: (a) Cl Cl Cl Cl (b) (c) (d) OH Cl Cl OH (e) (f) O Cl Cl O Cl Cl (g)

Determine whether each statement is true or false: (a) A racemic mixture of enantiomers is optically inactive. (b) A meso compound will have exactly one nonsuperimposable mirror image. (c) Rotating the Fischer projection of a molecule with a single chirality center by 90 will generate the enantiomer of the original Fischer projection: C A D B A C D B

When 0.075 g of penicillamine is dissolved in 10.0 mL of pyridine and placed in a sample cell 10.0 cm in length, the observed rotation at 20C (using the D line of sodium) is -0.47. Calculate the specific rotation of penicillamine.

(R)-Limonene is found in many citrus fruits, including oranges and lemons: For each of the following compounds identify whether it is (R)-limonene or its enantiomer, (S)-limonene: (a) (b) (c) (d)

Each of the following compounds possesses a plane of symmetry. Find the plane of symmetry in each compound. In some cases, you will need to rotate a single bond to place the molecule into a conformation where you can more readily see the plane of symmetry. (a) (b) HO OH (c) CH3 H3C H Br Br H (d) Cl H Me Cl Me H

cis-1,3-Dimethylcyclobutane has two planes of symmetry. Draw the compound and identify both planes of symmetry.

Consider the following two compounds. These compounds are stereoisomers of 1,2,3- trimethylcyclohexane. One of these compounds has three chirality centers, while the other compound has only two chirality centers. Identify which compound has only two chirality centers and explain why

For each of the following pairs of compounds, determine the relationship between the two compounds: (a) (b) H Me Cl Me HO H Cl Me H Me HO H (c) OH OH (d) (e) (f) (g) Cl Cl (h) (i) (j) (k) CH3 HO H CH3 CH3 HO H H OH H OH H OH CH3 HO H (l) Et HO H Me Et HO H H OH H OH H OH Me HO H

The specific rotation of (S)-carvone (at 20C) is +61. A chemist prepared a mixture of (R)-carvone and its enantiomer, and this mixture had an observed rotation of -55. (a) What is the specific rotation of (R)-carvone at 20C? (b) Calculate the % ee of this mixture. (c) What percentage of the mixture is (S)- carvone?

Identify whether each of the following compounds is chiral or achiral: (a) (b) Cl (c) (d) OH OH (e) OH OH (f) OH OH (g) Cl Cl (h) Cl Cl (i) (j) OH (k) (l) OH (m) OH (n) (o) (p

The specific rotation of vitamin C (using the D line of sodium, at 20C) is +24. Predict what the observed rotation would be for a solution containing 0.100 g of vitamin C dissolved in 10.0 mL of ethanol and placed in a sample cell with a length of 1.00 dm.

Determine whether each of the following compounds is optically active or optically inactive: (a) OH H Me OH Me H (b) H Me Cl Et H Me (c) CH3 HO OH H CH3 H (d) (e) H CH2OH OH HO H O H (f) CH2CH3 H CH3 CH3 H H (g) (h)

Draw bond-line structures using wedges and dashes for the following compounds: (a) CH3 HO H CH3 H OH H OH (b) Et HO H Me H OH H OH (c) Et HO H H OH Me HO H (d) H Me Cl Me HO H (e) Cl Me H Me HO H

The following questions apply to the five compounds in Problem 5.54. (a) Which compound is meso? (b) Would an equal mixture of compounds b and c be optically active? (c) Would an equal mixture of compounds d and e be optically active?

Draw a Fischer projection for each of the following compounds, placing the !CO2H group at the top: (a) OH O HO OH OH (b) OH OH O OH HO OH (c) OH OH O OH HO OH

For each of the following pairs of compounds, determine the relationship between the two compounds: (a) Et H Me H H Me (b)

It is possible for a compound to be chiral even though it lacks a carbon atom with four different groups. For example, consider the structure of the following compound which belongs to a class of compounds called allenes. This allene is chiral. Draw its enantiomer and explain why this compound is chiral. C C C Me H H M

Based on your analysis in the previous problem, determine whether the following allene is expected to be chiral: C C C Me Me H Me

As mentioned in Problem 5.58, some molecules are chiral even though they lack a chirality center. For example, consider the following two compounds and explain the source of chirality in each case: (a) PPh2 PPh2 (S)-BINAP (b)

The following compound is known to be chiral. Draw its enantiomer and explain the source of chirality. CH3 H H3C

The following compound is optically inactive. Explain why. O O H3C CH3

The following compound, whose central ring is referred to as a 1,2,4-trioxane, is an anticancer agent that demonstrates activity against canine osteosarcoma (J. Am. Chem. Soc. 2012, 134, 1355413557). Assign the configuration of each chirality center and then draw all possible stereoisomers of this compound, showing the specific stereochemical relationship between each of your drawings. O O O O H N H O

Coibacin B is a natural product that exhibits potent anti-inflammatory activity and potential activity in the treatment of leishmaniasis, a disease caused by certain parasites (Org. Lett. 2012, 14, 38783881): O O H H H (a) Assign the configuration of each chirality center in coibacin B. (b) Identify the number of possible stereoisomers for this compound, assuming that the geometry of the alkenes are fixed.

Chiral catalysts can be designed to favor the formation of a single enantiomer in reactions where a new chirality center is formed. Recently, a novel type of chiral copper catalyst was developed that is redox reconfigurable in that the S enantiomer of the product predominates when the CuI form of the catalyst is used, and the R enantiomer is the main product when the CuII form is used (see below). This is not a general phenomenon, and only works for a limited number of reactions (J. Am. Chem. Soc. 2012, 134, 80548057). O EtO EtO OEt OEt O NO2 Catalyst (CuI or CuII form) Base solvent NO2 O O + (a) Draw the major products that form when the CuI or the CuII catalyst is used, specifying the stereochemistry and the catalyst required to make each product. (b) Consider the chart below, which summarizes the results of the reaction using different solvents. For each solvent, calculate the %S and %R. Which solvent produces the optimal results? Solvent % ee of (S)-product % yield of product Toluene 24 55 Tetrahydrofuran 48 33 CH3CN 72 55 CHCl3 30 40 CH2Cl2 46 44 Hexane 51 30

In 2010 the structure of the compound (+)-trigonoliimine A (isolated from the leaves of a plant in the Yunnan province of China) was reported as shown below. In 2011, a synthesis of the reported structure was accomplished, and the configuration of a chirality center in the compound was found to have been incorrectly assigned in 2010 (J. Am. Chem. Soc. 2011, 133, 1076810771): N N N N OMe Reported structure of (+)-trigonoliimine A H (a) Draw the correct structure of (+)-trigonoliimine A and provide its absolute stereochemical configuration. (b) The 2011 synthesis enabled the investigators to determine that the original assignment of configuration (of the natural product) was incorrect. Explain how this determination could have been made.

Consider the reaction below, which involves both a dehydrogenation (removal of two neighboring hydrogen atoms) and a Diels-Alder reaction (which we will learn about in Chapter 17). Utilizing a specially designed catalyst, the achiral starting materials are converted to a total of four stereoisomeric productstwo major and two minor (J. Am. Chem. Soc. 2011, 133, 1489214895). One of the major products is shown: N O O O O N O O H H Catalyst O O + Stereoisomers +(a) Draw the other major product, which is the enantiomer of the product shown. (b) The two minor products retain the cis connectivity at the bridgehead carbons but differ from the major products in terms of the relative stereochemistry of the third chirality center. Draw the two minor products. (c) What is the relationship between the two minor products? (d) What is the relationship between the major products and the minor products? 5.68 When a toluene solution of the sugar-derived compound below is cooled, the molecules self-assemble into fibrous aggregates which work in concert with the surface tension of the solvent to form a stable gel (Langmuir, 2012, 28, 1403914044). Redraw the structure showing both nonaromatic rings in chair conformations with the bridgehead hydrogen atoms in axial positions. Be sure to conserve the correct absolute stereochemistry in your answer. O O O H H OH OH OCH3 H2N

When a toluene solution of the sugar-derived compound below is cooled, the molecules self- assemble into fibrous aggregates which work in concert with the surface tension of the solvent to form a stable gel (Langmuir, 2012, 28, 1403914044). Redraw the structure showing both nonaromatic rings in chair conformations with the bridgehead hydrogen atoms in axial positions. Be sure to conserve the correct absolute stereochemistry in your answer. O O O H H OH OH OCH3 H2N

A key step of the Wittig reaction (Chapter 20) involves the decomposition of an oxaphosphetane, such as A, into two products (J. Org. Chem. 1986, 51, 33023308). If both chirality centers in A have the R configuration, determine whether the CRC p bond in B will have a cis or trans configuration. A B PO Ph Ph Ph CH CH PO Ph Ph Ph +

Consider the structure of the following ketone (J. Org. Chem. 2001, 66, 20722077): O (a) Does this compound exhibit rotational symmetry? (b) Does this compound exhibit reflectional symmetry? (c) Is the compound chiral? If so, draw its enantiomer.

The natural product meloscine can be prepared via a 19-step synthesis, featuring the following allene (see Problems 5.58 and 5.59) as a key intermediate (Org. Lett. 2012, 14, 934937): C C C OSi(iPr)3 N N N Br O O O @ ! (a) Draw a Newman projection of the allene when viewed from the left side of the CRCRC unit. Note that in this case the front and back carbons of the Newman projection are not directly attached to each other but instead are separated by an intervening sp-hybridized carbon atom. (b) Draw the enantiomer of this compound in bond-line format (using wedges/dashes to show stereochemistry where appropriate) and as a Newman projection. (c) Draw two diastereomers of this compound in bond-line and Newman formats.

Each of 10 stereoisomeric sugar derivatives can be prepared via a multiple-step synthesis starting from either glucuronolactone 1D or its enantiomer 1L. Depending on the specific series of reactions used, the configuration at carbons 2, 3, and 5 can be selectively retained or inverted over the course of the synthesis. This protocol does not allow for inversion at C4, but selection of 1D or 1L allows access to products with either configuration at this chirality center (J. Org. Chem. 2012, 77, 77777792). O O O OH O O 1D (or enantiomer) N OH HO OH HO (10 possible stereoisomers) 1 2 3 4 5 6 6 5 43 2 1 H (a) Draw the structure of 1L. (b) How many stereoisomers of 1D are possible? (c) Draw the structures of the eight chiral products (as pairs of enantiomers) and the two achiral products. (d) Only four of the products (including the two achiral ones) can theoretically be prepared from either reactant, 1D or 1L. Identify these four compounds and explain your answer.