Three-Carbon Building Blocks

Propylene is, next to ethylene, the most important basic chemical to produce not only polypropylene but also other intermediates for example propylene oxide and acrylonitrile. Just like ethylene, propylene can be produced via a hydrocarbon feedstock produced from a biomass [35-37]. Bio-glycerol produced as a byproduct of biodiesel can be dehydrogenated to produce propylene [48]. Bio-based ethylene can be dimerized to produce n-butene, which can then react with remaining ethylene via metathesis to produce propylene [49]. The use of fermentation products of biomass such as 1-butanol [50] enables the formation of n-butene, followed by a subsequent methathesis [49]. Alternatively, hydrothermal carboxylate reforming of fermentation products such as butyric acid or 3-hydroxybutyrate is also proposed as a viable option to propylene [51]. 

Other direct fermentation products such as 1-propanol and 2-propanol [52] can, in principle, be used for the production of propylene by dehydration but little research has been carried out [16,18], 

Another route is the use of vegetable oils or fatty acids that can be fed into an enhanced fluid catalytic cracker (FCC) unit to produce propylene (see www.chemsystems.com, accessed 22 June 2013). 

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Propiolaldehyde diethyl acetal has found numerous synthetic applications in the literature which may be briefly summarized. The compound has been utilized in the synthesis of unsaturated and polyunsaturated acetals and aldehydes by alkylation of metal-lated derivatives, " by Cadiot-Chodkiewicz coupling with halo acetylenes, " and by reaction with organocuprates. Syntheses of heterocyclic compounds including pyrazoles, isoxazoles, triazoles, and pyrimidines have employed this three-carbon building block. Propiolaldehyde diethyl acetal has also been put to use in the synthesis of such natural products as polyacetylenes " and steroids. ... 

Hydroxypropionic Acid (3-HPA). Like the structurally isomeric lactic acid, 3-HPA constitutes a three-carbon building block with the potential of becoming a key intermediate for a variety of high-volume chemicals malonic and acrylic acids, methacrylate, acrylonitrile, 1,3-propanediol, and so forth.Thus, Cargill is developing a low-cost fermentation route by metabolic engineering of the microbial... 

Reactive three-carbon building blocks such as alkynones [32] and 1,3-diaryl pro-penones (chalcones) (for a review on the chemistry of 1,3-diaryl propenones, see e.g. [33]) which can react with bifunctional nucleophiles in a sequence of Michael addition and cyclocondensation open a facile access to five-, six-, and seven-membered heterocycles (Scheme 1). As a consequence, this general strategy has found broad application. However, standard syntheses of alkynones [34] and chalcones [33] are often harsh and require either strongly basic or strongly Lewis or Brpnsted acidic conditions. Therefore, the application in one-pot methodology, where delicately balanced reaction conditions are a prerequisite, is largely excluded. 

Scheme 1 Ynones and enones as three-carbon building blocks in heterocycle synthesis...

Alkynones are potent Michael acceptors in heterocyclic chemistry and many five-, six-, and seven-membered heterocycles can be synthesized from reactive, bifunctional three-carbon building blocks such as alkynones by classical heterocyclic chemistry [32]. Taking into account the mild, catalytic access to alkynones the coupling-addition-cyclocondensation sequence for multicomponent approaches to five-, six-, and seven-ring heterocycles lies at hand (Scheme 19). 

The Cl sequence introduced in Chap. 2.2 represents a mild and catalytic access to chalcones. l,3-Diarylprop-2-en-l-ones are bifunctional electrophilic Michael-systems and per se important three-carbon building blocks in synthetic heterocyclic chemistry [33]. Among many classes of five-, six-, and seven-membered heterocycles the underlying principle is always the Michael-addition-cyclocondensation sequence of chalcones and bifunctional nucleophiles [176-181, 222-229]. Furthermore, chalcones can also participate in cycloadditions, as dienophiles and dipolar-ophiles and furnish in the case of 1,3-dipolar cycloadditions with diazo alkanes pyrazolines [230, 231], with azides triazolines [232], with nitrones isoxazolidines [233] with azomethinylides pyrrolidines [234], or with nitriloxides isoxazolines [235]. Therefore, the mild, catalytic access to chalcones by the CIR excellently sets the stage for the development of consecutive MCRs based upon cyclocondensation strategies. 

The presence of two negative charges in close proximity makes this new reagent 174 extremely reactive. Its carbanionic sites, at C-1 and C-3, however, differ sharply in their nucleophilicity and reactivity. The different surroundings of the carbanionic centers in this system makes the carbanion at C-3 better stabilized than at C-1. Therefore, electrophilic attack should be directed primarily at C-1. In fact, the addition of one equivalent of an electrophile to a solution of 174 leads to a highly selective attack at the terminal carbon atom. The product of this reaction, 175, still retains a carbanionic center and with the addition of another electrophile the formation of a second bond occurs selectively at C-2. In this manner, the dianion 174 is an excellent three-carbon building block for the synthesis of ketones of type 176 or four-carbon building block for the synthesis of esters of the type 177. 

Cyclopropyldiphenylsulfonium tetrafluoroborates 89 are versatile three-carbon building blocks. " Upon reaction with base, e.g. sodium methylsulfinylmethylide in 1,2-dimethoxyethane or potassium hydroxide in dimethyl sulfoxide, these salts are converted into ylides 90 which readily react with ketones or acrylates to afford spiroepoxides 91 or spiro[2.2]pentane-l-carboxylates 92, respectively. -Similar reactions were observed with (dimethylamino)phenylsulfoxonium cyclopropylide. ... 

On the other hand, transition metal mediated conversions of heterofunctionalized cyclopropane derivatives can be used in the generation of three-carbon building blocks. Thus, starting from hydroxy- or siloxycyclopropanes and similar compounds, metal homoenolates can be generated and transformed in the presence of transition-metal complexes. ... 

Synthesis of a marine sterol, depresosterol (25), illustrates the utility of the homoenolate as a multifunctional, three-carbon building block. Homo-Reformatsky reaction between an alkoxytitanium homoenolate (11 Section 1.14.5.1) and an aldehyde (19) afforded the undesired Cram product (20) in a ratio of >6 1 (Scheme 29). Inversion of the stereochemistry at the sterically hindered C-22 position was achieved through internal solvolysis by taking advantage of the terminal ester function. Stereoselective hydroxymethylation of the lactone (22) followed by introduction of the C-26 and C-27 methyl groups to (23) afforded depresosterol (25). 

Epichlorohydrin is a valuable three-carbon building block for synthesis because... 

Alkynones [62] and 1,3-diaryl propenones (chalcones) [63] are reactive three-carbon building blocks that can be transformed into five-, six-, and seven-membered heterocycles with bifunctional nucleophiles in the sense of Michael addition and cyclocondensation. Therefore, a catalytic access to ynones [64] and enones [65] by Sonogashira alkynylation turned out to be a versatile entry to consecutive multicomponent syntheses of heterocycles. This reactivity-based concept has been considerably developed by the Muller group in the past decade. In several reviews, the major advancements of this one-pot methodology have been summarized [66]. Therefore, only very recent conceptual achievements with respect to sequentially Pd-catalyzed processes [7] will be considered here. 

The synthesis of additional one- to three-carbon building blocks is the fourth major area of application of alkali metal [ " CJcyanides (Figure 7.25). These include trimethylsUyl [ C]-cyanide, [ " CJcyanogen bromide, alkali metal [ " CJcyanates and [ " C]thiocyanates, triethyl... 

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