Alkenes synthetic targets

Figures 15.45 and 15.46 illustrate impressively that the significance of 1,3-dipolar cycloadditions extends beyond the synthesis of five-membered heterocycles. In fact, these reactions can provide a valuable tool in the approach to entirely different synthetic targets. In the cases at hand, one can view the 1,3-dipolar cycloaddition of nitrile oxides to alkenes as a ring-closure reaction and more specifically, as a means of generating interestingly functionalized five- and six-membered rings in a stereochemically defined fashion.

When the synthetic target is an alkene, consider using a Wittig reaction, because the location of the double bond is completely controlled (unlike an E2 elimination, in which a mixture of products is often formed). One carbon of the alkene was the electrophilic carbonyl carbon of an aldehyde or ketone and the other carbon of the alkene was the nucleophilic carbon of the ylide. Because either carbon of the alkene could come from the nucleophile and the other from the electrophile, there are often two ways to accomplish the synthesis. 

Given the high synthetic potential of this transformation, the last few years have witnessed the use of this method for the asymmetric cis dihydroxylation of more elaborate alkenes and/or the preparation of interesting synthetic targets. A selection is shown in Table 7. 

As shown above, the PKR has tremendous synthetic potential due to a rapid increase in synthetic complexity from simple starting materials. The frequent presence of five-membered rings in synthetic targets has led to numerous applications. In turn, these applications have inspired improved conditions that allow the PKR to occur under mild conditions with with predictable regiocontrol and stereocontrol. Efforts continue to optimize the reaction for improved alkene regiocontrol, absolute stereocontrol, expanded substrate scope (especially for unreactive alkenes and medium-size ring formation) and catalytic turnover. 

Purpose. The bromination of frans-cinnamic acid is carried out to obtain en/flzro-2,3-dibromo-3-phenylpropanoic acid, the direct precursor to 2 -bromo-styrene, which is the synthetic target of Sequence D. You wiU review the stereospecificity of the addition of molecular bromine to an alkene. 

FGIs (a) and (b) involve retrosynthetic transformation of the hydroxy to carbonyl group the third FGI (c) implies elimination of both OH groups to obtain alkene, the target molecules of the next generation. In the synthetic direction, this means that reduction of the C=0 group(s) or dihydroxylation of the C=C bond is required for rich 1,2-diols. 

Dipolar cydoadditions are one of the most useful synthetic methods to make stereochemically defined five-membered heterocydes. Although a variety of dia-stereoselective 1,3-dipolar cydoadditions have been well developed, enantioselec-tive versions are still limited [29]. Nitrones are important 1,3-dipoles that have been the target of catalyzed enantioselective reactions [66]. Three different approaches to catalyzed enantioselective reactions have been taken (1) activation of electron-defident alkenes by a chiral Lewis acid [23-26, 32-34, 67], (2) activation of nitrones in the reaction with ketene acetals [30, 31], and (3) coordination of both nitrones and allylic alcohols on a chiral catalyst [20]. Among these approaches, the dipole/HOMO-controlled reactions of electron-deficient alkenes are especially promising because a variety of combinations between chiral Lewis acids and electron-deficient alkenes have been well investigated in the study of catalyzed enantioselective Diels-Alder reactions. Enantioselectivities in catalyzed nitrone cydoadditions sometimes exceed 90% ee, but the efficiency of catalytic loading remains insufficient. 

The hydroformylation reaction ( oxo reaction ) of alkenes with hydrogen and carbon monoxide is established as an important industrial tool for the production of aldehydes ( oxo aldehydes ) and products derived there from [1-6]. This method also leads to synthetically useful aldehydes and more recently is widely applied in the synthesis of more complex target molecules [7-15,17], including stereoselective and asymmetric syntheses [18-22]. 

Much more challenging is the targetted introduction of carbon substituents at terminal olefins by means of cross metathesis. Because of the mild reaction conditions under which alkene metathesis proceeds, cross metathesis could become an extremely valuable tool for the synthetic chemist if the critical parameters for productive cross metathesis between different, functionalized olefins were understood. 

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