Three component ring transformation

Dicarbonyl compounds 19 surely behave as the excellent dinucleophilic reagents for the RTF reactions, however, only several kinds of RTF products can be obtained due to limited availability of these reagents. In order to improve the synthetic utility of the RTF reaction, other reagents such as simple ketones 22 must be used. In this case, another nucleophile or activating reagent should be employed, and this kind of RTF reaction is called three components ring transformation (TCRT) . 

A domino process based on the twofold addition of alkenyl anions to a squarate ester was used by Paquette and coworkers [96] for the total synthesis of the triqui-nane sesquiterpene hypnophilin (4-284). The three-component reaction of 4-281,4-282 and vinyl lithium gave primarily the trans- and cis-adducts A and B, which furnished D either by an electrocyclic ring opening/ring closure via C or a dianionic oxy-Cope rearrangement (Scheme 4.60). Further transformations led to E and F, which resulted in the formation of 4-283 on treatment with acid. 

Based on previous success in the Pauson-Khand reaction [43], Evans demonstrated a sequential approach to the synthesis of eight-membered rings, which involved a rhodium-catalyzed aUyhc amination reaction followed by carbocyclization, to effect a three-component couphng (Scheme 12.11). To date, this transformation is only the second example of a sequential rhodium-catalyzed reaction in which only temperature is used to modulate catalytic activity. 

This three-component domino cyclocondensation reaction is effected via ring transformation of an isolable intermediate in a one-pot procedure. 

A three-component expeditious synthesis of 3,6-diaryl-5-mercaptoperhydro-2-thioxo-l,3-thiazin-5-ones from 2-methyl-2-phenyl-l,3-oxathiolan-5-one, an aromatic aldehyde, and an N-aryldithiocarbamic acid has recently appeared [194]. The synthesis is diastereoselective and involves tandem Knoevenagel, Michael, and ring transformation reactions occurring under solvent-free MW irradiation conditions in a single pot (Scheme 8.81). 

For the [6 + 0] transformation, since one of the elements is zero it does not count as a component and so this transformation is a unimolecular reaction. A [2 + 2 + 2] transformation to form a six-membered ring involves three-bond disconnections and hence is a three-component coupling reaction. 

As shown in Scheme 1.46, a simple synthesis of complex fused 1,4-benzoxaz-epin-2-one derivatives 86 and 87 was aehieved via a three-component leaction of quinoline or isoquinoline, acetylene dicaiboxylic esters and l-(6-hydioxy-2-isopio-penyl-l-benzofman-yl)-l-ethanone in water, in the absence of aiy catalyst [68]. Presumably, this transformation proceeds via the initial formation of a 1 1 zwitter-ionic intermediate 88 from the Michael addition of isoquinohne (or quinolone) to the activated ester. A proton transfer reaction takes then place in which this species is protonatedby the phenol group in the l-(6-hydroxy-2-isopropenyl-l-benzofuran-yl)-l-ethanone substrate, and this is followed by a second Michael addition of the resulting phenoxide anion to the isoquinohnium ion to afford intermediate 88, containing benzofuryl and isoquinoline ring systems. This intermediate then undergoes... 

Prof. Hao s synthesis commenced with the copper(I) chloride-catalyzed oxidation of the tryptamine derivative to afford ketone 42 [74], A three-component Strecker-type reaction was designed to react the ketone 42 with tryptamine and TMSCN to finish the first ring closure. After examining a series of both Lewis acid and Bronsted acids, the authors found a catalytic amount of TMSOTf promoted the transformation and afforded nitrile intermediate 43, which is ready for the Houben-Hoesch-type cyclization [75]. Treatment by TfOH (trifluoromethanesulfonic acid) [76] in DCM and the... 

The syntheses of five-membered heterocycles containing three oxygen or sulfur atoms in the 1,2,3-positions can be classified into three groups (i) one-component syntheses, in which a suitable acyclic molecule is cyclized by linkage of two heteroatoms (ii) two-component syntheses, in which the ring is built up either by a [3 -f 2] process or a [4 -1-1] process and (iii) synthesis by transformation of another heterocyclic ring. 

The most commonly employed transformations for the construction of five-membered rings containing three sulfur or oxygen atoms in the 1,2,4-positions are shown in Table 11. These have attracted more interest than the syntheses from acyclic components. The rearrangement of a 1,2,3-trioxolane (primary ozonide) to a 1,2,4-trioxolane (secondary ozonide) is the most generally applicable method for preparation of this ring system and will be discussed further in Sections... 

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