Cleavage traceless

Therefore it has to be distinguished from traceless-cleavage. As the intramolecular step is in general faster than any intermolecular step, this strategy provides an additional purification step, because only cychzed structures are detached from the resin. The method of cyclative cleavage by nucleophihc displacement has been... 

In contrast to traceless cleavage, which releases only hydrocarbon-like molecules, multifunctional cleavage provides additional diversity of functional compounds in... 

The work by Armstrong was extended to include the room temperature resin capture of trisubstituted ethenes with a pendant boronate group.80 Modification of the amide linker above to a novel silyl-based one allowed for the traceless cleavage of superior analogues. 

The condensation reaction of immobilized ester enolates with imines has been reported to give (3-lactam resins in good yields and high diastereomeric excess (Scheme 49), [133]. Traceless cleavage from the linker system yielded the desired (3-lactams. 

The synthesis of monocyclic p-lactams via the ester-enolate imine condensation route has been reported to be carried out utilizing triazene esters (Scheme 54), [141], Esters were attached to benzylamine resin by a triazene linker employing the respective diazonium salts. Immobilized ester-enolates were reacted with various imines to give polymer-bound p-lactams in different substitution patterns. Traceless cleavage from the triazene linker yielded the desired p-lactams. 

The liquid-phase reaction conditions were followed on the solid phase (Scheme 33) without any problems. It is most probable that the reaction proceeds, as in liquid phase, via a dianion [135], The condensation reaction of 103b was carried out with a range of imines, all of which gave very good results concerning loading of the lactam resin 107 and purity of the cleaved diazonium salt 108 (Scheme 34). Conditions published to date [136] for traceless cleavage from a... 

Larger amounts of pyridine drastically enhanced the coupling reaction and loading of 118, but also led to an increased formation of Japp-Klingemann type by-products 120. Several procedures to transform the diazonium salts into traceless products were explored before the formation of pure (3-lactams. The best conditions for traceless cleavage turned out to be simplified Keumi conditions [147]. (Scheme 37-38)... 

We recently reported the synthesis of a perfluoroalkylsulfonyl linker attached to TentaGel resin 13 (Fig. 6), which proves to act in a fashion similar to triflates as we had hoped, and demonstrated its application for the traceless cleavage of phenols using palladium-catalyzed reduction and Suzuki cross-coupling reactions.3,4... 

Various imines and imine precursors reacted with immobilized ester-enolate-derived triazene esters 481 to give polymer-bounded azetidin-2-ones 482 (Scheme 68). The esters were bound to a benzylamine resin by a triazene linker employing diazonium salts. Traceless cleavage from the triazene linker yielded the desired azetidin-2-ones 483 <2002JOC8034>. 

The chromium carbonyl linkers 1.40 (98) and 1.41 (99) were prepared from commercial triphenylphospine resin and respectively from pre-formed p-arene chromium carbenes and Fischer chromium amino carbenes. Their SP elaboration is followed by cleavage with pyridine at reflux for 2 h (1.40) and with iodine in DCM for 1 h at rt (1.41) both linkers produce the desired compounds in good yields. A similar cobalt carbonyl linker 1.42 (100) was prepared as a mixmre of mono- (1.42a) and bis- (1.42b) phosphine complex, either from pre-formed alkyne complexes on triphenylphosphine resin or by direct alkyne loading on the bisphosphine cobalt complex traceless cleavage was obtained after SP transformations by aerial oxidation (DCM, O2, hp, 72 h, rt) and modified alkynes were released with good yields and... 

In 1996 the Kurth group described the first sold-phase Reissert reaction (Scheme 5) [42, 43]. Activation of a carboxylic acid functionalized resin to the corresponding acyl chloride, followed by treatment with isoquinoline and TMS-CN (14) afforded the resin-linked Reissert adduct 16. This intermediate was subsequently alkylated at the a-position by treatment with LDA and alkyl iodides 17. Some of these adducts were further manipulated, and finally the substituted isoquinolines 20 were conveniently released using a traceless cleavage with KOH/THF. 

This linker allows for the straightforward attachment of phenols as sulfonate esters and also for their use in reductive traceless cleavage and for C-C bond formations during the release from the support. Its efficiency was demonstrated in the synthesis of valsartan methyl ester by a multi-step solid-phase strategy [111]. 

This linker system is based on the principle that triazenes can be efficiently generated by reactions of diazonium salts with amines. Under basic conditions, these triazenes are stable, but they can be cleaved under mildly acidic conditions to regenerate a diazonium salt and an amine. Based on this system, originally pubhshed by Moore and Tour [151, 152], two different hnkers have been developed. In the so-called T1 variant (Scheme 63), a secondary amine is created on the sohd support and reacted with a diazonium salt to yield the triazene 136. After the synthetic manipulations leading to 137, the triazene is cleaved, resulting in the formation of the initial support and the desired product [153]. Besides the traceless cleavage from the support, the diazonium salt formed as intermediate during the... 

Scheme 3.17 Fiuorous variants of the Ugi (above) and Bigineiii muiti-component reactions (beloiv) enabie the purification of the primary fluorous condensation products (not shown in this scheme) by simple two- or three-phase extraction, followed by "traceless" cleavage of the fluorous silyl tag with TBAF [5].

Tin hydride reagents are versatile tools for the functionalization of alkenes and alkynes. Based on this concept, Nicolaou and coworkers developed a polymer-bound tin hydride (118) that reacts via Pd-catalyzed hydrostannylation (or nucleophilic attack on the tin chloride with a vinyl lithium) with alkynes to give alkenylstannanes [116]. After further transformation to derivatives 119, the resin-bound substrates undergo proteolytic traceless cleavage to yield unsubstituted alkenes 120. Alternatively, the stannane can be employed for intramolecular Shlle coupling to produce macrolactones 121 in the cleavage step (Scheme 16.28). 

Scheme 16.35 Ring-closing metathesis used for traceless cleavage by Maarseveen et al.

Polystyrene-sulfonyl hydrazide resins 153 reacted with various amines to give regiospecifically 1,4-disubstituted-l,2,3-triazoles 154 via traceless cleavage reactions <04TL6129>. A library of peptidotriazoles were prepared by solid-phase peptide synthesis combined with a regiospecific copper(I)-catalyzed 1,3-dipolar cycloaddition between resin-bound alkynes and protected amino azides <04JCO312>. 

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