Ammonia chemoselectivity

A similar synthesis of enantiopure (l )-sulfinamides 123 from indane-derived toluenesulfonyl 1,2,3-oxathiazolidine-2-oxide 121 has been developed. This method includes chemoselective ring opening with inversion of configuration at the sulfur atom, using Grignard reagent at the first step and lithium amide in liquid ammonia in the second step (Scheme 17) <2002JA7880>. Intermediate stable and crystalline sulfinate esters 122 were isolated in >95% yield in diastereopure form. 

It is difficult to determine directly whether the electron transfer to an alkyne is a reversible or an irreversible reaction (Figure 17.83, top). The current thinking on the matter is that it is a reversible process. However, compounds containing two C=C triple bonds that are not too far apart can be reduced chemoselectively with Na in liquid ammonia such that only one of the C=C triple bonds is reduced. Figure 17.84 depicts the example of the dialkyne A. Such a... 

The normal synthetic pathway for hydroboration is reaction with an ambiphilic nucleophile of which the simplest example is hydroperoxide ion. This elicits a 1,2-migration of an alkyl group from boron to oxygen with concurrent loss of hydroxide ion. The step occurs with essentially complete retention of configuration. In similar vein, ambiphilic species with the structure NH2X may be used in amination, so that the overall reaction is an addition of ammonia to the alkene with the regio- and chemoselectivity driven by the hydroboration step. A majority of reactions of organoboranes can be rationalized in terms of these ionic mechanistic pathways, or closely related protocols (Scheme 2). 

Chemoselective primary amine synthesis is directly from ketones and ammonia, and is a very challenging project [316], TolBINAP-Ru complex can catalyze the reductive amination of certain ketones to give the corresponding amines in up to 95% e.e. (Eq. 2.39) [317]. 

Many other examples of chemoselective enone reduction in the presence of other reducible functionalities have been reported. For instance, the C—S bonds of many sulfides and thioketals are readily cleaved by dissolving metals. " Yet, there are examples of conjugate reduction of enones in the presence of a thioalkyl ether group." " Selective enone reduction in the presence of a reducible nitrile group was illustrated with another steroidal enone. While carboxylic acids, because of salt formation, are not reduced by dissolving metals, esters" and amides are easily reduced to saturated alcohols and aldehydes or alcohols, respectively. However, metal-ammonia reduction of enones is faster than that of either esters or amides. This allows selective enone reduction in the presence of esters"" and amides - -" using short reaction times and limited amounts of lithium in ammonia. 

Catalytic hydrogenation of an enone would not be chemoselective if an isolated double bond were also present in the molecule. However, isolated double bonds are inert to dissolving metal reduction. On the other hand, a variety of functional groups are reduced with alkali metals in liquid ammonia. These include alkynes, conjugated dienes, allylic, or benzylic halides and ethers. 

Commercially, pyridine is prepared by the gas phase, high-temperature reaction of crotonaldehyde, formaldehyde, steam, air, and ammonia over a silica-alumina catalyst in 60-70% yield. However, in the laboratory, the challenge is in the preparation of substituted pyridine derivatives in a process that allows one to control regioselectivity and chemoselectivity in the most efficient manner. In this regard the utility of palladium-catalyzed cross-coupling reactions has enabled synthetic chemists by providing the ability to construct highly diversified pyridine derivatives in an efficient fashion [2]. 

A collection of results obtained with the most effective catalyst systems is summarized in Figure 6.4. Noteworthy examples include the oxidation of a-aminoalcohols with no loss in enantiopurity and the oxidation of cis-allyhc alcohols without Z E isomerization. Stahl also demonstrated the chemoselective oxidation of primary diols to form lactones [22]. While ABNO provides efficient oxidation of symmetric diols, TEMPO discriminates between subtle steric differences in nonsymmetrical substituted diols. Cu/nitroxyl catalysts have also been applied to a variety of tandem reactions [23], perhaps the most noteworthy of which is the conversion of primary alcohols to nitriles via in situ condensation of ammonia with the aldehyde and subsequent dehydrogenation of the primary imine to the nitrile (Figure 6.5) [24]. 

Amides, carbamates, imides, and their metal salts also serve as reactive nucleophiles (Scheme 3). Sodium p-toluenesulfonamide attacks l-acetoxy -chloro-cyclohex-2-ene to give an allylic amide in a highly chemoselective manner with retention of conflgura-tion.t Sodium salt of methylcarbamate is also alkylated in DMSO or HMPAJ ° (A, 0)-Bis-fer-Boc hydroxylamine reacts with an aUylic carbonate chemo- and regioselectively to provide a protected A-allylhydroxylamine, in which an ethoxy anion, a counterion of Pd in a 7r-allylpalladium complex, serves to generate an anion of (A, 0)-bis-ter-Boc hydroxylamine.f Preparation of primary allylamines by a selective monoallylation of ammonia is not possible and they are prepared by indirect methods. The monoallylation... 

Carroll and coworkers developed a metal-free phenylation of anilines with diphenyUodonium trifluoroacetates in DMF at 130 °C [91]. A thorough chemoselectivity study with anilines and diaryliodonium triflates was later performed by the Olofsson group, revealing that electronics are more important than sterics in this transformation, and hence that both the mesityl and the trimethoxyphenyl groups are suitable dummy groups [27]. Carbazoles were efficiently aiylated in toluene at 50 °C in the presence of BuOK [92], and anilines could be obtained in aqueous ammonia at 80 °C (Scheme 5a) [93]. 

This chapter covers recent developments in the title area published during 2014. As last year, little work has appeared in the literature apart from the preparation of novel pentacoordinated compounds. For instance, a chemoselective synthesis of 2,2,2-trichloro-4(5)-(dichloro-phosphoryloxy)-l,3,2X -benzodioxaphospholes which were obtained in a multi-step reaction starting from 1,2,3- and l,2,4-tris(trimethyl-siloxy)benzenes has been reported. Of note also are investigations describing intramolecular N-H cleavage of ammonia, allg lamines and aryl amines by tricoordinate phosphorus compounds furnishing pentacoordinated adducts. 

---