Amino alcohols from alkenes

N-Nitrosopiperidine (carcinogen) with oxygen adds photolytically to alkenes to give A(-(2-nitro-alkyl)piperidines. Indirect methods of preparing amino alcohols from alkenes include the well-known trans opening of epoxides with nitrogen nucleophiles and a recent, complementary, cis opening of... 

Sharpless asymmetric aminohydroxylation One-pot enantioselective synthesis of protected vicinal amino alcohols from simple alkenes. 404... 

The final step can involve introduction of the amino group or of the carbonyl group. o-Nitrobenzyl aldehydes and ketones are useful intermediates which undergo cyclization and aromatization upon reduction. The carbonyl group can also be introduced by oxidation of alcohols or alkenes or by ozonolysis. There are also examples of preparing indoles from o-aminophcnyl-acetonitriles by partial reduction of the cyano group. 

As described in Section 2.3.2, vinylaziridines are versatile intermediates for the stereoselective synthesis of (E)-alkene dipeptide isosteres. One of the simplest methods for the synthesis of alkene isosteres such as 242 and 243 via aziridine derivatives of type 240 and 241 (Scheme 2.59) involves the use of chiral anti- and syn-amino alcohols 238 and 239, synthesizable in turn from various chiral amino aldehydes 237. However, when a chiral N-protected amino aldehyde derived from a natural ot-amino acid is treated with an organometallic reagent such as vinylmag-nesium bromide, a mixture of anti- and syn-amino alcohols 238 and 239 is always obtained. Highly stereoselective syntheses of either anti- or syn-amino alcohols 238 or 239, and hence 2,3-trans- or 2,3-as-3-alkyl-2-vinylaziridines 240 or 241, from readily available amino aldehydes 237 had thus hitherto been difficult. Ibuka and coworkers overcame this difficulty by developing an extremely useful epimerization of vinylaziridines. Palladium(0)-catalyzed reactions of 2,3-trons-2-vinylaziri-dines 240 afforded the thermodynamically more stable 2,3-cis isomers 241 predominantly over 240 (241 240 >94 6) through 7i-allylpalladium intermediates, in accordance with ab initio calculations [29]. This epimerization allowed a highly stereoselective synthesis of (E) -alkene dipeptide isosteres 243 with the desired L,L-... 

P-Amino alcohols can be prepared by treatment of an alkene with a reagent prepared from HgO and HBF4 along with aniline to give an ami nomercurial... 

The mechanism of 1,3-dipolar cycloaddition can be found in Ref. 63 and the references within. The reaction of nitrone with 1,2-disubstituted alkenes creates three contiguous asymmetric centers, in which the geometric relationship of the substituents of alkenes is retained. The synthetic utility of nitrone adducts is mainly due to their conversion into various important compounds. For instance, P-amino alcohols can be obtained from isoxazolidines by reduction with H2-Pd or Raney Ni with retention of configuration at the chiral center (Eq. 8.44). 

From oxidative cleavage of 1,2-diols and 1,2-amino alcohols Dibutyltin oxide, 95 By reaction of alkyl halides with sulfur-stabilized carbanions Methylthiomethyl p-tolyl sulfone, 192 From reduction of carboxylic acids Vilsmeier reagent, 341 From terminal alkenes by addition reactions... 

A vincinal amino alcohol grouping is present in a fair number of natural products which possess useful biological activity, such as antibiotics122. Such a functionality has been produced from alkenes via osmium-mediated aminohydroxylation (equation 22)123. The reaction proceeds in 40-97% yield and is enantioselective if chiral osmium-Cinchona alkaloid complexes are used to mediate the reaction. 

In combination with the range of standard transformations of alcohols, alkenes, and vinylsulfides, these silicon-tethered additions of functionalized radicals offer a versatile and stereoselective approach to amino alcohol synthesis. Whereas vinyl and 2-oxoethyl radicals have not yet been demonstrated as competent participants in the various intermolecular additions reported in the literature, the temporary tether approach allows such functionalized fragments to be installed in an efficient and stereoselective manner. Synthesis of the aminosugar daunosamine from achiral precursors shows how this concept, employing hydrazone radical acceptors, can be merged with asymmetric catalysis to achieve practical synthetic advances. 

A route to pyrroles illustrated by the preparation of 292 involves initial treatment of the nitroketene-5, 5 -acetal 293 with an organometallic reagent, followed by conversion of the resulting alkene 294 to the enamine 295, and final annulation to the target heterocycle (Scheme 34) <1998T12973>. A related approach featuring constmction of /3-hydroxyenamines from 1,3-dicarbonyl compounds and /3-amino alcohols, and subsequent palladium-catalyzed cyclization to pyrroles, has been reported <1996TL9203>. 

Dipolar cycloadditions between nitrones and alkenes to give isoxazolines are very important reactions in organic synthesis, because 1,3-amino alcohols can be synthesized from isoxazoline derivatives. Jprgensen and co-workers reported catalytic asymmetric... 

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