From bicyclic amines

Imines were preferentially formed and the carbon-carbon bond was selectively formed at the C(2) position of the cyclic amine. With ethylene and propene, only imines were formed but with more bulky olefins and 7-membered cyclic amines, reduction to 2-alkyl cyclic amine took place, and N-alkylation was also observed from bicyclic amine. 

Aziridinocyclopropanes 163 derived from 2-phenylsulfonyl-l,3-dienes undergo BF3-induced rearrangement to bicyclic amines 165, which feature the skeleton of the tropane alkaloids. The reaction proceeds via cyclopropyl carbinyl cation 164, an intermediate also invoked in the analogous epoxide rearrangements. Trapping by fluoride ion is a competing pathway <96TL3371>. 

The enantioselectivity of Sn(II) enolate reactions can be controlled by chiral diamine additives. These reagents are particularly effective for silyl thioketene acetals.162 Several diamines derived from proline have been explored and l-methyl-2-(l-piperidinomethyl)pyrrolidine 21 is an example. Even higher enantioselectivity can be achieved by attachment of bicyclic amines to the pyrrolidinomethyl group.163... 

A similar scaffold for the preparation of peptidomimetics was prepared by Mitsunobu cyclization of the molecule coming from the coupling of 4-benzylprolinol and iV-nosyl(o-nitrobenzensulfonyl) tryptophan 316 (Scheme 41). A Mitsunobu cyclization occurred easily due to the acidity of the NH of the nosyl group that could be further selectively deprotected under very mild conditions. The so-formed bicyclic amine 317 can be further coupled with different amino acids to give compounds 318, employed in the search of a new somatostatin pharmacophore <2005BML4033>. 

The synthesis and properties of nitramines derived from strained and bicyclic amines are discussed in more detail in Chapter 6. Such compounds often exhibit high performance resulting from high crystal densities and/or high heats of formation due to internal strain. 

Illustrative of the results which might be expected in using macro-cyclic compounds to separate cations having similar chemical properties in biological systems is the report of Muller (49) involving removal of 85Sr from rats using the bicyclic amine synthesized by Dietrich et al. 

Carbohydrate azidolactones were converted to bicyclic amines (from an N3R moiety to H3N-R) by TPAP/NMO/PMS/CH3CN as part of a synthesis of 1-ep/hyantocidin from D-ribose [166]. Thymidine-specific depyrimidination of DNA by this and... 

An essential step in the process is the (reversible) formation of the anion RO . Alkylacetylenes, which are less acidic than most other acetylenic derivatives, react less readily. We found that the oxidation of alkylacetylenes such as C2H5C3CH can be carried out at a convenient rate when to the solution in pyridine a small amount of diazabicycloundecene (DBU) is added. This condensed bicyclic amine is a stronger base than other amines and is expected to facilitate the proton removal from the acetylene. 

Sodium hypochlorite reacts with (1) to give the 1-chloro derivative, which gives rise to a variety of products, including the bicyclic amine, pyrrolizidine, when treated with silver salts (72CJCH67). Quaternary salts derived from (3) react with sodium methoxide to give mostly the acyclic Hofmann elimination product (83%) minor amounts of (3) (14%) are also formed, together with a trace (2%) of the product of 5N2 attack on the a-methylene carbon (80JOC3952). 

The prochiral aziridine 1 is easily prepared from cyclooctene. Paul Muller of the University of Geneva has shown (Helv. Chim. Acta 2004,87,227) that metalation of 1 in the presence of the chiral amine sparteine leads to the bicyclic amine 3 in 15% , by way of intramolecular C-H insertion by the intermediate chiral carbene 2. The sparteine can be recovered and recycled. 

Nitroanilines give the product fluoronitrobenzenes in poor yield under standard conditions but, as the acetamido moiety is compatible with such conditions, 3-fluoroaniline is better reached from 3-acetamidoaniline (54 % yield with a dediazoniation step at 50-60 C).31 Bicyclic amines can be treated in the same way (82% yield from 1-naphthylamine).4... 

Enamines are also potential ketones and accordingly have been used as the ketonic component in this type of pyrylium synthesis (63AG(E)394). The initial adducts, which form pyrylium salts on treatment with perchloric acid, are similar to those derived from secondary amines and pyrylium salts. The significant feature of this variant is that it gives access to pyrylium compounds which are unsubstituted at the 4- and 6-positions but which carry substituents at C-2 and C-5. More conventional enamines, such as 1-piperidinocyclohexene, afford bicyclic pyrylium salts (652), whilst polycyclic salts (653) result if cyclic chlorovinyl ketones are used. 

Quantum yields for isomerization of t-1 to c-1 via intersystem crossing are similar to those obtained in triplet sensitization, indicating that t is formed with near unit efficiency. Similar results were reported for the interaction of t with inorganic anion electron donors (127b). Rate constants for intersystem crossing of the t-1-ethyldiisopropylamine and triethylamine exciplexes obtained from the measured exciplex lifetimes are 5 x 107 s"1 (116), similar to the values for the exciplexes of pyrene (128) and naphthalene (121) with triethylamine. Larger intersystem crossing rate constants are observed for the exciplexes of t-1 with the bicyclic amines l-azabicyclo[2.2.2]-... 

Another important function of protecting groups is to prevent a reagent from attacking itself. In the last chapter, when we discussed the synthesis of the bicyclic amine monomorine, we used the protected enone 12 but did not say how it was made. The chloroketone 9 is first made1 in 89-93% yield from the ketolactone 6 simply by reaction with HC1. Chloride displaces the protonated ester group 7 and the product 8 decarboxylates under the conditions of the reaction. 

Efrapeptins such as efrapeptin D (24 in Figure 5) were isolated from the entomopathogenic fungus Tolypocladium niveum. They have a unique linear peptide structure with a bicyclic amine moiety at their C-terminus and show insect toxicity by inhibiting mitochondrial ATPase.7... 

---