Roberts, Caserio - Basic Principles of Organic Chemistry (2nd edition, 1977)
.pdf13-7 Building the Carbon Skeleton |
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First, we can see that the carbon skeleton of the desired product can be divided to give the following combinations of fragments:
Next, we have to decide what reaction or reactions would be useful to put these fragments together to reform the C, chain. If we look at the list of available reactions in Table 13-44for C-C bond formation, we can rule out 1, 2, 4, 8, and 9: 1 and 4 because the reactions are unsuitable for making unbranched chains; 8 and 9 because they make rings, not chains; and 2 because it does not work well in the absence of activating groups. Reaction 3 could be used to combine C, and C7 units to give C,, as by the radical addition of CBrCl, to 1-heptene:
Reactions 6 and 7 could also be used to make C,, 6 by linking C, to C, and 7 by putting together two C, units.5
,You may wish to review the sections cited for each reaction to be sure you understand the judgments we make here as to the suitability of particular reactions for the purpose at hand.
5Reaction 7 could also be used to make C, by other combinations, such as of C, and
C3,but these would give undesirable mixtures of products. Thus, C-C-C-C=CH |
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+ H C s C - C |
C-C-C-CsC-CsC-C |
+ C-CGC-CsC-C |
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c - c - C - C ~ C - C ~ C - C - C - c .
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13 Polyfunctional Compounds. Alkadienes. Approaches to Organic Synthesis |
Either of these two reactions provides a simple and straightforward way of converting 2-octyne to cis-2-octene, so a satisfactory answer to the original problem is
1. R2BH
2. CH3CH2C02H or H,, Pd-Pb
You can see that even with having available only seven C-C |
bond- |
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H |
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forming reactions and two ways of converting -C= C - |
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--+ C= C , a |
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considerable amount of logical screening is required to eliminate unsuitable possibilities. The skilled practitioner makes this kind of diagnosis quickly in his head; at the outset you will find it useful to write the steps in your screening in the same way as we have done for this example.
13-8 INTRODUCING FUNCTIONALITY
As we have seen in the previous section, it may be easy to construct the carbon skeleton of the target compound of a synthesis, but with a reactive functional group at the wrong carbon. Therefore it is important also to have practice at shifting reactive entry points around to achieve the final desired product. We shall illustrate this form of molecular chess with reactions from previous chapters. A typical problem may be to devise syntheses for achieving the following conversions :
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13 Polyfunctional Compounds. Alkadienes. Approaches to Organic Synthesis |
13-9 CONSTRUCTION OF RING SYSTEMS BY CYCLOADDITION REACTIONS
Another example of a synthesis problem makes use of the cycloaddition reactions discussed in this chapter. Consider the synthesis of bicyclo [2.2. I] heptane, 9, from compounds with fewer carbons.
bicyclo [2.2.l]heptane, 9
Whenever a ring has to be constructed, you should consider the possibility of cycloaddition reactions, especially [4 +21 cycloaddition by the Diels-Alder reaction. A first glance at 9, written in the usual sawhorse-perspective formula, might lead to overlooking the possibility of constructing the skeleton by [4 +21 addition, because the compound seems only to be made up of five-membered rings. If the structure is rewritten as 10, the six-membered ring stands out much more clearly:
@bicyclo C2.2.11heptane, 10
If we now try to divide the six-membered ring into [2] and [4] fragments, we find that there are only two diferent ways this can be done:
The left division corresponds to a simple [4 +21 cycloaddition, whereas the right division corresponds to a complex reaction involving formation of three ring bonds at once. Actual Diels-Alder reactions require diene and dienophile starting materials, and two possibilities, using 1,3-cyclopentadiene as the diene and ethene or ethyne as dienophile, follow:
H
C |
/C"*~H |
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111 |
+ CH, |
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-+ |
c |
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,CH |
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H |
CH' |
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13 Polyfunctional Compounds. Alkadienes. Approaches to Organic Synthesis |
Exercise 13-18 Indicate how you would synthesize each of the following compounds from ethene, propene, 2-methylpropene, or 2-methylpropane, and appropriate inorganic reagents. Specify reagents and the reaction conditions, and justify the practicality of any isomer separations. If separations are not readily possible, estimate the proportion of the desired compound in the final product.
CH3 |
CH3 |
CH3 |
CM, |
I |
I |
I |
I |
d. CH3-C-CH2-C-CH3 |
i. HOCH,-CH-CH,-C-CH3 |
I |
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I |
I |
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CH3 |
I |
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CH3 |
Exercise 13-19 Assume that it is necessary to synthesize meso-l,4-diphenyl-2,3- butanediol. How could you do this if the only organic reagents at your disposal are methylbenzene and ethyne? In devising a suitable scheme, use any inorganic reagents you consider necessary and specify the reaction conditions (catalysts, solvent, use of acids or bases, and temperature) as closely as possible.
Exercise 13-20 The following key intermediates can be used in a synthesis of cyclo- tetradeca-l,3,8,10-tetrayne. Write the reagents and conditions for achieving transformations between the key intermediates. Be as specific as possjble. Notice that more than one step may be involved in any given transformation.