Piperidine formamidines

An a-substituted piperidine formamidine may be metalated at the a -position selectively, but the alkylation is not stereoselective, providing a 1 1 mixture of cis and trans stereoisomers, as illustrated in Scheme 10. ... 

To conclude the section, we recall that ligands somewhat related to dpa also give rise to linear trinuclear complexes. This is the case of 2,6-bis(phenylamino)pyridine,36 2,6-bis(phenylamino)piperidine,37 and bis (2-pyridyl)formamidine.38 At the moment, however, no (significant) electrochemical investigation has been carried out on their metal complexes. 

A few linear tetranuclear complexes of ligands related to dpa have been structurally characterised, namely [Ni4(phdpda)4] (phdpda = dianion of A-phenyldipyridylamine),39 [Cu4(dphip)4]2 + (dphip = anion of 2,6-bis(phenylamino)piperidine),37b and [Cr4(dpf)4Cl2]2+ (dpf = anion of bis(2-pyridyl)formamidine),38 but no pertinent electrochemical investigation is available. 

A variety of amidines react with nitromalonaldehyde in presence of Triton B or piperidine, to form the 5-nitropyrimidines 116 [Eq. (37)].106-110 Yields range from 30 to 90%. Acetamidine gives a very poor yield of the nitropyrimidine and formamidine does not give any isolable product. 

Similariy low face-selecdvity was found in die addition of lithiated formamidines of tetrahydroquin-oline, dihydroindole and p-carboline to benzaldehyde, although addition of the lithiated 3-car-boline to methyl chloropropyl ketone afforded an 8.5 1 selectivity (Scheme 48). Lithiated formamidines of pyrrolidine and piperidine also add to benzaldehyde in excellent yield, but the diastereoselectivity was not reported. ... 

The addition of amines to isonitriles, catalyzed by copper compounds, furnishes formamidines. The method has found further application, e.g. piperidine was added to benzeneisonitrile or to trimethylsi-lylmethaneisonitrile to give the amidine (321 Scheme 53). A -Sulfonylformamidines (322) were the... 

Metalated piperidine amides and formamidines may be converted to a-alkylated piperidines, as illustrated in Scheme 9. Again, the two examples illustrate the superiority of the formamidine moiety in both yield and ease of removal. 

Heterocycles Acetylacetone. N-Aminophthalimide. Boron trichloride. Dichloro-formoxime. Oicyanodiamide. Dicyclohexylcarbodiimide. Dietboxymethyl acetate. Diethyl oxalate. Diketene. Dimethylformaniide diethylacetal. Diphenyldiazomethene. Ethyl ethoxy-methylenecyanoacetate. Formaldehyde. Formamide. Formamidine acetate. Formic acid. Glyoxal. Hydrazine. Hydrazoic acid. Hydroxylamine. Hydroxylamine-O-sulfonic acid. Methyl vinyl ketone. o-Phenylenediamine. Phenylhydrazine. Phosphorus pentasullide. Piperidine. Folyphosphoric acid. Potassium diazomethanedisulfonate. Sodium ethoxide. Sodium nitrite. Sodium thiocyanate. Tetracyanoethylene. Thiosemicarbozide. Thiourea. Triethyl orthoformate. Tris-formaminomethane. Trityl perchlorate. Urea. Vinyl triphenyl-phosphonium bromide. 

The 4-acetyl-3,5-dioxo-l-methylcyclohexane carboxylic acid (ADCC) linker 2n [128] was developed to provide a support for anchoring primary amines via a preformed handle method. The anchor is stable toward acids and bases including piperidine and l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and is thus compatible with Fmoc chemistry. The amine can be released by rapid hydrazinolysis on treatment with 2% hydrazine in DMF. A formamidine linker 2o has been obtained from Merrifield resin by reaction with the appropriate phenol. Secondary amines can be anchored to the support by an amidine exchange reaction and after further transformations cleaved by treatment with hydrazine [129]. 

Meyers and co-workers have continued their studies to exploit the synthetic potential of a-lithio-formamidines and have now described an efficient synthesis of 2-aryl- or 2-heteroaryl-pyrrolidines and -piperidines (266 ). " Alkylation of formamidines (264) gives intermediates (265) which cyclize in situ after cleavage of the amidine unit. The aza-Wittig reaction has been utilized in a general synthesis of heterocyclic vinylogous ure-thanes and amides (268). Staudinger reaction of azides (267)... 

Proton removal adjacent to a heteroatom is further facilitated if the lithium can be internally coordinated to proximate electron donors, such as the carbonyl oxygen, permitting the formation of dipole-stabilized carbanions. Thus lithiations of various amides, thioamides, imides, esters, Boc derivatives of cyclic amines (pyrrolidines, piperidines, and hexahydroaze-pines), thioesters, )V,iV-dialkylthiocarbamates, and various formamidine derivatives are achieved conveniently using s-BuLi (eqs i3 i7) 32,43b.44.47a,48a Subsequent addition of electrophiles followed by hydrolytic removal of the activating carbonyl, carbamoyl, or formamidine moiety provides a valuable synthetic route to a variety of a-substituted amines, alcohols, and thiols. Successful alkylation of the dipole-stabilized car-banions may require the conversion of the initial lithio carban-ions into their organocuprate derivatives, e.g. by the addition of n-PrC=CCu. ... 

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