Alkene from amine oxides

Staurosporine (173) has been converted to the 4, 5 -alkene via amine oxide pyrolysis the alkene was hydroxylated, and also subjected to hydrobora-tion-oxidation to give regioselectively the 5 -a-alcohol. Various other subsequent manipulations at the 4 - and 5 -positions were also reported. 4 -iV-Methyl-5 -hydroxystaurosporine and 5 -hydroxystaurosporine are new in-dolocarbazoles that have been isolated from a marine Micromonospora strain. ... 

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). 

The primary products obtained from 2-butanol are of mechanistic. significance and may be compared with other eliminations in the sec-butyl system 87). The direction of elimination does not follow the Hofmann rule 88) nor is it governed by statistical factors. The latter would predict 60% 1-butene and 40% 2-butene. The greater amount of 2-alkene and especially the unusual predominance of the cis-olefin over the trans isomer rules out a concerted cis elimination, in which steric factors invariably hinder the formation of cis-olefin. For example, the following ratios oicisjtrans 2-butene are obtained on pyrolysis of 2-butyl compounds acetate, 0.53 89, 90) xanthate, 0.45 (S7) and amine oxide, 0.57 86) whereas dehydration of 2-butanol over the alkali-free alumina (P) gave a cisjtrans ratio of 4.3 (Fig. 3). 

Nitroso compounds are formed during the addition of nitrous oxide," " dinitrogen trioxide, and nitrosyl halides to alkenes, and in some cases, from incomplete oxidation of amines with peroxyacids like peroxyacetic acid. Quenching of carbanions with nitrosyl halides is also a route to nitroso compounds. A full discussion on this subject is beyond the scope of this work and so the readers are directed to the work of Boyer. ... 

Another argument against the oxo-transfer mechanism in our catalytic aerobic oxidation protocol is the lack of formation of sulfoxides from sulfides, N-oxydes from amines and phosphine oxydes from phosphines. Alkenes also proved to be inert towards oxidation no epoxide formation could be detected under our reaction conditions. 

Hydroaminomethylation reactions can be accomplished by addition of nucleophilic a-amino alkyl radicals (generated from amines) onto electron-deficient alkenes [7, 21], Amines have a low oxidation potential, and are easily oxidized by excited aromatic ketones bearing electron-donating substituents (e.g., Michler s ketone) or... 

When the unsaturated tertiary amine, pitprofen (179 R = H) is treated with MCPBA the reaction takes place selectively at the mwe nucleophilic nitrogen to furnish the corresponding amine oxide with the alkene moiety intact. In contrast, peroxycarboximidic acid, prepared in situ from acetonitrile/H202. reacts selectively with the alkene moiety of the ester (179 R = Me equation 65). The sterically hindered nitrogen of (179) is able to react with peroxy acids which have a low steric demand, but not with peroxy-caiixrximidic acids which have a large steric demand. 

The utility of reductive amination with NaBHsCN in synthesis is contained in reviews and successful applications have been compiled through 1978. Table 7 provides a variety of examples taken from more recent accounts and chosen to illustrate the versatility and compatibility of the process with diverse structural types and chemoselectivity demands. Thus, esters (entries 2-4, 8-12), amides (entries 3, 6-9, 12), nitro groups (entry 13), alkenes (entry 2), cyclopropyl groups (entry 2), organometallics (entry 5), amine oxides (entry 14) and various heterocyclic rings (entries 1, 3, 5-10) all survive intact. Entry 6 illustrates that deuterium can be conveniently inserted via the readily available NaBDjCN, and entry 15 demonstrates that double reductive amination with diones can be utilized to afford cyclic amines. 

The purpose of preparing aliphatic amine oxides is usually their thermal decomposition to cis alkenes and N,N-dialkylhydroxylamines (Cope rearrangement) [156, 161, 1187]. Thus A, A -dimethylcyclohexylmethylamine is oxidized with 30% hydrogen peroxide in methanol to its oxide, whose decomposition at 90-100 °C at 10 mm of Hg and at 160 °C for 2 h furnishes 79-88% of methylenecyclohexane and 78-90% of A, A -dimethylhydroxyl-amine [161], Another example is the preparation of cw-cyclooctene from dimethylcyclooctylamine (equation 502) [1187]. 

The thermal decomposition of sulfoxides whose sulfur atom is attached to the a carbons of ketones or esters leads to a,(3-unsaturated ketones or esters, respectively, via a cis elimination. The reaction is reminiscent of alkene formation by Cope elimination of dialkylhydroxylamines from tertiary amine oxides (equation 567) [321]. 

As with amine oxides and sulfoxides, acyclic 1,2-disubstituted alkenes are usually obtained with the ( )-stereochemistry, although the formation of a,(3-unsaturated nitriles is reported to give a mixture of ( )- and (Z)-isomers. For cyclic alkenes, the stereochemistry of double bond formation depends upon ring size. However, it can be affected by conformational factors, e.g. cyclododecyl phenyl selenide gives a mixture of cis- and fra/is-cyclododecenes on oxidative elimination (equation 38) but only the (El-isomer (101) was obtained from the acetoxycyclododecyl selenide (100 equation 39). ... 

Cope reaction The thermal cleavage of an amine oxide to produce an alkene and a hydroxylamine. The amine oxide is usually formed in situ from the amine and an oxidising agent. 

Brown s crotyl borane 158 (chapter 24) provides reagent control through a chair-like six-membered ring in the formation of 159. Oxidation of the alkene (ozone with oxidative workup) gives the free acid marked in 160 and on removal of the benzylic group the freed amine (circled) cyclises to it to give the pyrrolidone required (147 as its methyl ester). The synthesis can easily be completed from there. 

Epoxidation and Dihydroxylation of Alkenes There are several ways to convert alkenes to diols. Some of these methods proceed by syn addition, but others lead to anti addition. An important example of syn addition is osmium tetroxide-catalyzed dihydroxylation. This reaction is best carried out using a catalytic amount of OSO4, under conditions where it is reoxidized by a stoichiometric oxidant. Currently, the most common oxidants are f-butyl hydroperoxide, potassium ferricyanide, or an amine oxide. The two oxygens are added from the same side of the double bond. The key step in the reaction mechanism is a [3 + 2] cycloaddition that ensures the syn addition. 

Ketones are also produced from amines by oxidation with KMn04 supported on copper(II) sulfate pentahydrate in dichloromethane. Bridged alkenes such as norbornene are cleaved with the same reagent. This method is an alternative to ozonolysis. ... 

---