Alkene-amines, formation

Photochemical reactions of nitrogen-containing thiocarbonyl compounds ([2 + 2] cycloaddition to alkenes with formation of thietanes, transformations of thioimides to lactams and cyclic amines, cyclizations of thioamides) 03H(59)399. 

Aryliodine(ni) derivatives have found a wide range of application in organic synthesis, particularly for oxidative functionalization of alkenes, amines, carbonyl derivatives, phenols. 2,i3,i5,25 Among the various mechanisms which have been invoked to explain these transformations, the ligand coupling mechanism has been implied in a number of these reactions carbon-carbon bond formation, carbonyl a-fimctionalisation, hydrazone a-functionalisation. 

Phosphorinanones have been utilized as substrates for the preparation of alkenes/ amines,indoles, - and in the synthesis of a series of secondary and tertiary alcohols via reduction,and by reaction with Grignard and Refor-matsky - reagents. Phosphorinanones have also been used as precursors to a series of 1,4-disubstituted phosphor ins. The use of 4-amino-l,2,5,6-tetrahydro-l-phenylphosphorin-3-carbonitrile for the direct formation of phosphorino-[4,3-< ] pyrimidines has been reported. ... 

Keywords Alkenes Amination Arenes C-N bond formation Iodine-nitrogen... 

Cationic rhodium complexes catalyse the oxidative anti-Markovnikov amination of aromatic alkenes to enamines, a process that is accompanied by a simultaneous formation of 1 equiv. of ethylbenzene. Kinetic and mechanistic studies reveal that the yield and the rate of the reaction increase on increasing the styrene amine ratio. Furthermore, the type of phosphine ligand greatly influences the reaction. The formation of cationic rhodium-alkene-amine complexes has been proposed to be the first step towards the active catalytic species. ... 

With respect to the intermolecular nitrene addition to alkenes, the formation of aziridines is generally observed. Nevertheless, the use of sulfonimidamides has allowed the discovery of a highly chemoselective intermolecular aUylic C(sp )-H amination that can be applied to several classes of alkenes. Various terpenes and aUyl enol carbonates, particularly, undergo allylic amination in excellent yields of up to 98% (Scheme 28). The chemoselectivity was supposed to be controlled by the substrate. Hyperconjugation of the aUylic C—H bonds with the adjacent Jt-system would increase their reactivity, a result corroborated by the exclusive formation of the aziridine from P-caryophyUene whose structure does not display such a hyperconjugative effect for the aUylic C—H bonds. 

Interestingly, the reaction is chemoselective and oxidation of alkene-amines gave the N-oxides selectively without any epoxide formation. One example is given in Eq. (20). A number of substituted pyridines were also oxidized to the pyridine N-oxides by DMD in quantitative yields [94]. 

In addition to the preparation of l-alkenes, the hydrogenolysis of allylic compounds with formate is used for the protection and deprotection of carboxylic acids, alcohols, and amines as allyl derivatives (see Section 2.9). 

As another example of nitrene formation, the reaction of o-nitrostilbene (96) with CO in the presence of SnCU affords 2-phenylindole (97). The reaction is explained by nitrene formation by deoxygenation of the nitro group with CO, followed by the addition of the nitrene to alkene. Similarly, the 2//-indazole derivative 99 was prepared by reductive cyclization of the A-(2-nitrobenzyli-dene)amine 98[89]. 

Hydroperoxides have been obtained from the autoxidation of alkanes, aralkanes, alkenes, ketones, enols, hydrazones, aromatic amines, amides, ethers, acetals, alcohols, and organomineral compounds, eg, Grignard reagents (10,45). In autoxidations involving hydrazones, double-bond migration occurs with the formation of hydroperoxy—azo compounds via free-radical chain processes (10,59) (eq. 20). 

Oxaziridines are generally formed by the action of a peracid on a combination of a carbonyl compound and an amine, either as a Schiff base (243) or a simple mixture. Yields are between 65 and 90%. Although oxygenation of Schiff bases is formally analogous to epoxidation of alkenes, the true mechanism is still under discussion. More favored than an epoxidation-type mechanism is formation of a condensation product (244), from which an acyloxy group is displaced with formation of an O—N bond. 

An alkene activated by an electron-withdrawing group—often an acrylic ester 2 is used—can react with an aldehyde or ketone 1 in the presence of catalytic amounts of a tertiary amine, to yield an a-hydroxyalkylated product. This reaction, known as the Baylis-Hillman reaction, leads to the formation of useful multifunctional products, e.g. o -methylene-/3-hydroxy carbonyl compounds 3 with a chiral carbon center and various options for consecutive reactions. 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

With a common intermediate from the Medicinal Chemistry synthesis now in hand in enantiomerically upgraded form, optimization of the conversion to the amine was addressed, with particular emphasis on safety evaluation of the azide displacement step (Scheme 9.7). Hence, alcohol 6 was reacted with methanesul-fonyl chloride in the presence of triethylamine to afford a 95% yield of the desired mesylate as an oil. Displacement of the mesylate using sodium azide in DMF afforded azide 7 in around 85% assay yield. However, a major by-product of the reaction was found to be alkene 17, formed from an elimination pathway with concomitant formation of the hazardous hydrazoic acid. To evaluate this potential safety hazard for process scale-up, online FTIR was used to monitor the presence of hydrazoic acid in the head-space, confirming that this was indeed formed during the reaction [7]. It was also observed that the amount of hydrazoic acid in the headspace could be completely suppressed by the addition of an organic base such as diisopropylethylamine to the reaction, with the use of inorganic bases such as... 

A variant of the BISBI ligand system is the NAPHOS ligand, which as expected gives similar levels of n-selectivity in the course of the hydroformylation of terminal alkenes. Interesting is a hydroformylation in the presence of secondary amines which allows a mild and selective one-pot hydroformy-lation/enamine formation (Scheme 13) [58]. 

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