Guanidines, addition from amines

Guanidines have been prepared by a wide variety of methods, of which two are of much greater importance than the others. These two methods, (a) the addition of amines to cyanamides and (b) the displacement of an alkylmercaptan by an amine from an alkylisothiouronium salt, together with close variants, are discussed first, and this discussion is followed by a survey of less frequently used procedures. 

Cyanamides like 4 (from amines and cyanogen bromide) provide access to guanidines. This approach allows for introduction of different substituents, and alkylating intermediates can further increase the diversity of products produced. However, high temperatures are required, especially with aromatic amines, for the final addition to give the guanidine products (Scheme 5).9... 

We added the acetylene to aldehyde 12 now because this step is not compatible with a protected guanidine. Treatment of 43 with EtMgBr to form the acetylide and addition of aldehyde 12 afforded 54% of 45 and 32% of 44. Under the basic conditions, the secondary amine adds to the carbamate to form the oxazolidinone ring. The decrease in the geminal coupling constant of the methylene hydrogens adjacent to the nitrogen from 11 Hz in 43 to 8 Hz in oxazolidinone 45 is characteristic of the... 

Pd(0)/phosphine complexes, or their precursors, in the presence of a suitable co-base, have also been shown to promote, in good yields (66-100%), the formation of allylic carbamates from various primary and secondary aliphatic amines, pressurized C02 and allylic chlorides, in THF, at ambient temperature [87a]. The choice of the added co-base (Base), used for generating the carbamate salt RR NC02 (BaseH)+, was found to be critical for high yields of O-allylic urethanes. The use of a guanidine (CyTMG) or amidine (DBU) base was optimal for this system (see also Section 6.3.1). ft is assumed that this chemistry passes catalytically through a mechanism similar to that illustrated in Scheme 6.19. This involves nucleophilic attack by carbamate anion on a (tt-allyl) palladium species, formed by the oxidative addition of the allylic chloride to a palladium(O) intermediate. 

The triazene T2 linker14 and the improved T2 linker57 systems offer a unique approach to the formation of guanidines in which all three substituents can be varied to a wide extent. Starting from disubstituted triazene on the T2 linker, deprotonation using NaH/DMF and subsequently acylation by the addition of isothiocyanates (Scheme 12) yielded a library of resin-bound thioureas. For the reaction of the thioureas with amines, the use... 

Similar chiral catalysts 7 were used in the Michael addition of glycine derivatives to acrylic esters to obtain functionalised oc-aminoacids5 here, the guanidines were prepared from chiral amines or diamines in one step but using cyanogen bromide, which is a noxious reagent (Figure 4). 

In special cases the reaction of the anions of carbon acids at the enaminone carbonyl group in a 1,2-addition can be forced by acetalization. For example, a tertiary amino-methylenelactone can thus be attacked by the anion derived from cyanoacetamide. Substitution of the tertiary amine in a second step yields tetrahydrofuropyridone in good yield. Reaction of thiourea or guanidine leads to fused pyrimidines247 (equation 179). 

Guanidines are also obtained from carbodiimides (which are isomeric with cyanamides) since these react extremely readily with ammonia or amines. Thus, for instance, 7V,7V/,7V//-triphenylguanidine is formed exothermally when diphenylcarbodiimide is mixed with aniline.47 The analogous addition of phenylhydrazine to diphenylcarbodiimide, giving A,A -diphenyl-A"-(phenyl-amino)guanidine, forms the first step in the synthesis of nitrone.48... 

The excellent reviews of Berlinck [1-5] have surveyed a great number of guanidine-type natural products. In addition, some guanidine-derived marine alkaloids have been reviewed by Kobayashi and Ishibashi [6,7]. Also, a recent book gave accounts of marine alkaloids including the phakellins, palau amines and oroidin-like dimers derived from bromopyrroles and polyketide-derived polycyclic guanidine alkaloids [8]. 

Additionally, the use of Rh2(esp)2 has extended the intramolecular C(sp )—H amination reaction to other types of nitrene precursors (Scheme 11). Appfication of the reaction conditions to ureas and guanidines, thus, gives access to valuable building blocks for the synthesis of drug candidates or natural products.A diverse range of 1,3- and 1,2-diamines is, also, easily accessible, respectively from sulfamides and hydroxylamine-derived sulfamates.In each case, 1—2 mol% of catalyst 3 is sufficient to isolate the expected cycfic products with excellent yields of up to 99%. 

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