Amides protecting amines

A number of people must be thanked for their contributions and help in completing this project. I am grateful to Gordon Bundy, who loaned me this card file, which provided many references that the computer failed to find, and to Bob Williams, Spencer Knapp, and Tohm Fukuyama for many references on amine and amide protection. I thank Theo Greene who checked and rechecked the manuscript for spelling and consistency and for the herculean task of checking all the references to make sure my 3s and 8s and 7s and 9s were not interchanged, all w iihout... 

Researchers at Merck Co. [35] who, together with scientists from Solvias, had developed the enantioselective hydrogenation of unprotected enamine amides and esters [36], reported a more recent example of product inhibition. The product amine amide or ester was found to be an inhibitor of the catalyst, and indeed instances of catalyst poisoning by amines have been reported several times (see later). The authors also found an excellent solution to this problem the addition of BOC-anhydride to the hydrogenation reaction neatly reacts away all the amine to form the BOC-protected amine, whereas the enamine was left unreacted (Scheme 44.4). This addition resulted in a remarkable rate enhancement [35]. 

We have previously seen how cyclic lactams can be synthesized by installing a protected amine in one of the Ugi or Passerini components, followed by cyclization onto the isocyanide-derived amide, taking advantage of the particular reactivity of convertible isocyanides. The same type of compounds can be accessed through nucleophilic attack of the amine onto an ester moiety, suitably installed as additional function into another component. This strategy has been widely used for the preparation of diketopiperazines 104 (Fig. 22), a typical privileged structure, starting with... 

Usually, amides 7 are prepared from acids 6 and amines. C. Gtirtler of Bayer MaterialScience AG in Leverkusen reports (Tetrahedron Lett. 2004,45, 2515) the develop of catalysts for the alternative condensation of an acid 6 with an isocyanate 4. It is particularly exciting that isocyanates are intermediates in the one-carbon degradation of an acid 3 to the corresponding amine. Current practice, if the protected amine were desired, is that the intermediate isocyanate 4 would be trapped with an alcohol, leading to the urethane 5. This newly-reported observation offers the alternative of ending with the amide 7, or perhaps with the sulfonamide 9. 

Various functional groups can be protected and released in high yields, such as alcohols (as ethers), carboxylic acids (as esters), amides (as amides), and amines (as carbamates). In the latter case, however, two drawbacks must be noted ... 

Alkyl-4-oxo-l,3-dioxolanes, to protect a-hydroxy carboxy groups, 267 5-Alkyl-4-oxo-l,3-dioxolanes, to protect a-hydroxy carboxy groups, 267 4-Alkyl-5-oxo-l,3-oxazolidines, to protect carboxy groups, 266-267 Allyl alcohols, to protect, 18 iV-Allylamides, to protect amides, 154, 397 /V-Allylamines, to protect amines, 362 Allyl carbamates, to protect amines, 248, 252, 331-332... 

Amines, protection of, 309-405 as amides, 348-362 Reactivity Chart 9, 445-449 as carbamates, 315-348 Reactivity Chart 8, 441-444 as special derivatives, 362-385 Reactivity Chart 10, 449-452 Amino acetal derivatives, to protect amines, 392-394... 

Carboxylic acids, protection of, 224-276 as amides and hydrazides, 270-276 as esters, 227-270 Reactivity Chart 6, 433-436 S-Carboxymethyl thioethers, to protect thiophenols, 294-295 Catechols, protection of, 170-174 as cyclic acetals and ketals, 170-172 as cyclic esters, 173-174 Reactivity Chart 4, 425-428 CBZ, see Benzyl carbamates Chloroacetamides, to protect amines, 352-353... 

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