Disconnections polarity reversal

In the same way, disconnection of a 1,4-diketone requires either an acyl anion equivalent reacting with a normal /3-carbonyl electrophile or a normal o -carbonyl nucleophile reacting with an abnormal cr-carbonyl electrophile. These abnormal or reversed-polarity reagents are said to have umpolung reactivity. 

In chapter 10 we compared C-C disconnections with related two-group C-X disconnections, mainly at the alcohol oxidation level. In this chapter we deal more fully with carbonyl compounds, chiefly aldehydes and ketones, by two related disconnections. We start by comparing the acylation of heteroatoms by acid derivatives such as esters (a 1,1-diX disconnection 1 that can also be described as a one-group C-X disconnection) with the acylation of carbon nucleophiles and move on to compare the 1,2-diX disconnection 3 with the alkylation of enolates 6. Here we have reversed the polarity. We mention regioselectivity—a theme we shall develop in chapter 14. 

The first disconnection for any a, 3-unsaturated carbonyl compound 21 is an FGI reversing the dehydration. We could suggest two alcohols 22 or 25 but we much prefer the 1,3-diO relationship in 22 to the 1,2-diO in 25 as the synthesis of compounds with odd numbered relationships needs synthons of only natural polarity (chapter 18). 

You might think you could escape this problem by choosing the alternative disconnection 8, but this is not so. We have more choice here we can use the a3 synthon 7 with natural polarity, in real life an enone, but then we shall have to use the acyl anion equivalents 6 that we met in chapter 23. Reversing the polarity gives us the naturally polarised electrophile, an a1 synthon 9 represented by an acylating agent and the homoenolate, or d3 synthon, 10 with unnatural polarity. 

However, the chemists who were conducting this investigation were not able to get this particular Grignard reaction to work. Therefore, a different approach was needed. Again, using analysis similar to that given earlier, they developed a route based on the same disconnection, but with reverse polarity ... 

This scheme refers to a very general approach as the respective allylic electrophiles e.g. halides) are readily available, easy to handle, and capable of reacting with various carbanionic species (Scheme 2.36). Below we will consider also a less common, but nevertheless very useful, disconnection of this moiety which leads to reversed polarity of the components. 

Disconnection of the enone 86 by the strategy we have just used for 74, with the reverse polarity, gives the unsaturated acid 87 again accessible by a Wittig reaction with the protected reagent 89. We have in mind using an alkyl-lithium instead of a vinyl-lithium as a nucleophile to make 86. 

When zeolites are dealuminated by steam-calcination part of the framework A1 is extracted and generates extra-framework species (EFAL) that can be cationic, anionic or neutral. Some of these EFAL species can act as Lewis acid sites [19] or can influence the Brpnsted acidity, by either neutralizing Brpnsted acid sites by cation exchange, or by increasing the acidity by a polarization effect and/or by withdrawing electron density from lattice oxygens [20-22]. However, under mild steaming the A1 can also become partially, and reversibly, disconnected from the lattice [23]. This opens the way to Lewis acid catalysis by the A1 [24]. 

Aldehyde (24) is a 1,5-difunctionalised compound but it cannot be made by a Michael reaction. Disconnection (a) still looks the best so we might consider reconnecting the aldehyde in (23) and reversing the polarity of disconnection... 

If the carbon atom in 3 is electrophilic, then the carbon in 2 must be nucleophilic. This assumption is based on simple bond polarization and it makes it possible to correlate the imaginary 3 with a carbonyl compound that has an electrophilic carbon with a polarized C-0 bond. Nucleophilic acyl addition to a ketone is a known reaction, so 3 correlates with a real molecule—acetone. If 3 correlates with an electrophilic center, then 2 must be a nucleophilic center and an alkyne anion is a reasonable choice. It is known that an alkyne anion will react with a ketone via acyl addition (see Chapter 18, Section 18.3.2). The correlation of 2 with an alkyne simply requires adding a hydrogen atom to the red carbon to give terminal alkyne, 7. Conversion of alkyne 7 to the anion, followed by acyl addition to acetone, should lead to 1. Disconnection of 1 generates acetone and 7, and the reaction of 7 and acetone leads to 1. Recognizing the forward and reverse relationships is essential for correlating the disconnection (retrosynthesis) with the reactions that make the bond (synthesis). 

Consider the electrochemical cells illustrated in Figure 5.4. When the circuit is disconnected current does not flow and the ceU is at thermodynamics equilibrium. However, when current flows the ceU is polarized and the forward (cathodic) and reverse (anodic) currents and potential at the electrodes have the following conditions... 

Figure 16.17. Bilayer morphologies of a bicontinuous mesophase (P) of Types 1 and 2. (a) Type 1 bicontinuous mesophases consist of a reversed, polar (e.g. water-filled) film (thickness 2t ) folded on to the P surface, immersed in two disconnected but interwoven apolar (paraffin) continua, with one on either side of the surface, (b) Type 2 phases contain a paraffin film of thickness twice the chain length, 2/, separating polar domains...

It is therefore necessary to use an umpolung (reverse polarity) reagent in place of one of the usual components. A nitro group on a carbon facilitates the removal of a proton from that carbon, giving a nucleophilic nitronate anion suitable for the 1,2 disconnection. Later the nitro group and carbon may be converted to a carbonyl group (which itself would have been electrophilic). 2,5-Heptanedione was prepared in this way (Eq. 8.9) [14]. 

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