Alkynes retrosynthetic analysis

The result of the retrosynthetic analysis of rac-lO is 2-hydroxyphenazine (9) and the terpenoid unit rac-23, which may be linked by ether formation [29]. The rac-23 component can be dissected into the alkyl halide rac-24 and the (E)-vinyl halide 25. A Pd(0)-catalyzed sp -sp coupling reaction is meant to ensure both the reaction of rac-24 and 25 and the ( )-geometry of the C-6, C-7 double bond. Following Negishi, 25 is accessible via carboalumination from alkyne 27, which might be traced back to (E,E)-farnesyl acetone (28). The idea was to produce 9 in accordance with one of the methods reported in the literature, and to obtain rac-24 in a few steps from symmetrical 3-methyl-pentane-1,5-diol (26) by selective functionalization of either of the two hydroxyl groups. 

Let us now give some thought to Myers retrosynthetic analysis of 4 (Scheme 8.1). After a partial clearance of reactive epoxide functionality from within 4, Myers disconnected bond a in compound 5 to yield the partially protected diyne 7 and ketone 6 as possible building blocks. Note how one of the terminal alkyne units in 7 has been retrosynthetically protected with a r-butyldimethylsilyl group to permit regiospecific alkynyl... 

First we note that it is necessary to form a carbon-carbon bond because the starting material has only two carbons and the target has seven. Because the starting material is an alkyne, we can probably use an acetylide anion as the nucleophile to form the carbon-carbon bond (see Section 10.8). How can a ketone functional group be introduced Section 11.6 described the hydration of an alkyne to produce a ketone. Our retrosynthetic analysis then becomes ... 

Using retrosynthetic analysis, we recognize that the c/.v-epoxide can be prepared from the c/s-alkene. The m-alkene can be prepared by catalytic hydrogenation of an alkyne. Finally, substituted alkynes can be prepared by nucleophilic substitution reactions using acetylide ion nucleophiles (see Section 10.8). On the basis of this analysis, the synthesis reported in the literature was accomplished as shown in Figure 23.3. 

Chapter 8 begins the treatment of organic reactions with a discussion of nucleophilic substitution reactions. Elimination reactions are treated separately in Chapter 9 to make each chapter more manageable. Chapter 10 discusses synthetic uses of substitution and elimination reactions and introduces retrosynthetic analysis. Although this chapter contains many reactions, students have learned to identify the electrophile, leaving group, and nucleophile or base from Chapters 8 and 9. so they do not have to rely as much on memorization. Chapter 11 covers electrophilic additions to alkenes and alkynes. The behavior of carbocations, presented in Chapter 8, is very useful here. An additional section on synthesis has been added to this chapter as well. 

Use retrosynthetic analysis to solve multistep synthesis problems with alkynes as reagents, intermediates, or products. 

It s often a good idea to start retrosynthetic analysis of target molecules containing isolated double bonds by considering FGI to the alkyne because C-C disconnections can then become quite easy. 

The brief report of Jacobsen s total synthesis starts with a detailed retrosynthetic analysis. The compound was broken into four pieces 21a after removal of the phosphate. The unsaturated lactone 24 (M is a metal) could be made by an asymmetric oxo-Diels-Alder reaction from diene 22 and ynal 23. The epoxide 25 provides a second source of asymmetry. One cis alkene comes from an alkyne 26 and the rest from a dienyl tin derivative 27. 

If the azine structure is considered by itself, then the retrosynthetic analysis can start at the imine structural element (H2O addition O -> C-2, retrosynthetic path a). Suggestions for the cyclocondensation of various intermediates arise based on the 5-aminopentadienal or -one system 145, and further (path g, NH3 loss) on pent-2-endial (glutaconic dialdehyde) or its corresponding diketone 146. Consideration of a retro-cycloaddition (operation c) leads to the conclusion that a synthesis of pyridines by a cocyclooligomerization of alkynes with nitriles is possible. 

It s often a good idea to start retrosynthetic analysis of target molecules containing isolated double bonds by considering FGI to the alkyne because C—C disconnections can then become quite easy. The cis-alkene below is an intermediate in the synthesis of a component of violet oil. FGI to the alkyne reveals two further disconnections that make use of alkyne alkylations. The reagent we need for the first of these is, of course, the epoxide as there is a 1,2-relationship between the OH group and the alkyne. 

In this chapter we described methods for the synthesis of alkenes using dehydrohalogenation, dehydration of alcohols, and reduction of alkynes. We also introduced the alkylation of alkynide anions as a method for forming new carbon-carbon bonds, and we introduced retrosynthetic analysis as a means of logically planning an organic synthesis. 

The retrosynthetic analysis is outlined in Scheme 22. The amide was introduced by the Curtius rearrangement, and the macrolide 117 was formed by Horner-Emmons macrocyclization at the C2-C3 bond. The C17-C18 bond was constructed by the ring-opening of epoxide 118. 119 was formed via the Kocienski-Julia olefination at the C8-C9 bond. The cis-2,6-disubstituted tetrahydropyran in 120 was constructed by the Petasis-Ferrier rearrangement. The C4-C5 (Z)-trisubstituted alkene in 121 was formed by carbomet-allation to an alkyne. 

As we have seen many times in this chapter, the only method we have learned for achieving this transformation is the alkylation of a terminal alkyne. Our synthesis must therefore involve an alkylation step. This should be taken into account when performing a retrosynthetic analysis. 

Continuing with a retrosynthetic analysis, we must consider the step that might be used to produce the alkyne. Recall that our synthesis must contain a step involving the alkylation of an alkyne. We therefore propose the following retrosynthetic step ... 

Scheme 9.6 Retrosynthetic analysis for the synthesis of herbindole, identification of an intramolecular [2+2+2] catalytic cycloaddition of alkynes as a key step [11].

Propose reasonable syntheses of each of the following aUcynes, using the principles of retrosynthetic analysis. Each alkyne func-... 

Metathesis reactions are very powerful tools to create C—C bonds and provide synthetic chemists with synthetic design based on an unprecedented retrosynthetic analysis of complex compounds in very elegant and efficient ways. As the impact of metathesis in modern synthetic chemistry of drug and natural product is evidenced by a number of publications and reviews, in this chapter, we describe the most illustrative strategies of metathesis and their applications to drug and natural product syntheses in line with types of olefin, enyne, and alkyne metathesis reactions. 

In the synthesis of the polyketide metabolite citreofuran (57), RCAM was incorporated into the retrosynthetic analysis by setting an alkyne-one as the precursor for the furan ring. The diyne precursor 55 was rapidly assembled from acid 51 by its reaction with chloroenamine 52 to yield the alkoxyisocoumarin 53 upon treatment with Et3N. The addition of homopropargylic Grignard 54 to unstable 53 resulted in... 

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