Dieckmann condensation cyclization

Potassium Amides. The strong, extremely soluble, stable, and nonnucleophilic potassium amide base (42), potassium hexamethyldisilazane [40949-94-8] (KHMDS), KN [Si(CH2]2, pX = 28, has been developed and commercialized. KHMDS, ideal for regio/stereospecific deprotonation and enolization reactions for less acidic compounds, is available in both THF and toluene solutions. It has demonstrated benefits for reactions involving kinetic enolates (43), alkylation and acylation (44), Wittig reaction (45), epoxidation (46), Ireland-Claison rearrangement (47,48), isomerization (49,50), Darzen reaction (51), Dieckmann condensation (52), cyclization (53), chain and ring expansion (54,55), and elimination (56). 

In its present form, intermediate 12 is not a viable substrate for the crucial Dieckmann condensation it must undergo prior epimerization at C-16. When intermediate 12 is treated with sodium methoxide in hot methanol, enolization at C-16 occurs and an equilibrium is established between 12 and a diastereomeric substance, intermediate 11. Once formed, 11 can either revert back to 12 through the planar enolate form, or it can participate in a productive cyclization reaction to give a new six-membered ring. Under these conditions, the desired transformations take place with exceptional facility to give, after acidification of the reaction medium, enol ester 10. 

Condensations Highly atom economical since small molecules of water or alcohol are liberated Atom economy increases as the molecular weights of the combining fragments increases For cyclization reactions such as the Dieckmann condensation and the synthesis of cyclic ethers from straight chain diols the atom economy increases with increasing ring size... 

The intramolecular version of ester condensation is called the Dieckmann condensation.217 It is an important method for the formation of five- and six-membered rings and has occasionally been used for formation of larger rings. As ester condensation is reversible, product structure is governed by thermodynamic control, and in situations where more than one product can be formed, the product is derived from the most stable enolate. An example of this effect is the cyclization of the diester 25.218 Only 27 is formed, because 26 cannot be converted to a stable enolate. If 26, synthesized by another method, is subjected to the conditions of the cyclization, it is isomerized to 27 by the reversible condensation mechanism. 

Dieckmann Condensation The intramolecular equivalent of a Claisen condensation where dicarboxylic acid ester undergoes base-catalyzed cyclization to form a P-keto ester. 

A majority of routes leading to bicyclic pyridoazepines schematically falls into four categories (Scheme 3) They can be described as 1.2 or 2.1 cyclizations, each of them basing on a pyridine (7a and b, respectively) or an azepine derivative (7c and d, respectively). Among the synthetic methods involved are classical ones (N-alkylation, lactamization, Dieckmann condensation, etc.) and an increasing part of enamine, enamide, and... 

The first cyclative cleavage of a small molecule was Crowley and Rapo-port s study41 of intramolecular Dieckmann condensations on solid phase (Fig. 13), which was complicated by the reversible nature of the cyclization. Despite the unique opportunities afforded by C-C rather than C-X bond formation during cleavage, there are few examples from the combinatorial age. A modern version of the Claisen-type condensation by Kulkarni and Ganesan42 uses a strongly acidic active methylene group to ensure unidirectional cyclization, and furnishes tetramic acids with three points of diversity. 

The utilization of the Mitsunobu reaction and Dieckmann condensation has been demonstrated for the highly efficient and enantioselective synthesis of loracarbef, starting from the unnatural amino acid (2.V,J .y)-2-amino-3-hydroxy-6-heptenoic acid <2000T5667, 2003TL5991> (Scheme 30). The cyclization step from monocyclic... 

Cyclization of suitably substituted thiophenes (308) to yield thieno[3,4-6]furans (309) or (310) was achieved by utilization of the Dieckmann condensation (Equation (3)) <86JCS(P1)2223>. 

Key Mechanism 22-12 The Claisen Ester Condensation 1071 22-13 The Dieckmann Condensation A Claisen Cyclization 1074 22-14 Crossed Claisen Condensations 1074 22-15 Syntheses Using /3-Dicarbonyl Compounds 1077 22-16 The Malonic Ester Synthesis 1079 22-17 The Acetoacetic Ester Synthesis 1082 22-18 Conjugate Additions The Michael Reaction 1085 Mechanism 22-13 1,2-Addition and 1,4-Addition (Conjugate Addition) 1085... 

An internal Claisen condensation of a diester forms a ring. Such an internal Claisen cyclization is called a Dieckmann condensation or a Dieckmann cyclization. Five- and six-membered rings are easily formed by Dieckmann condensations. Rings smaller than five carbons or larger than six carbons are rarely formed by this method. 

The Claisen ester condensation (Sections 22-12 through 22-14) (Cyclizations are the Dieckmann condensation.)... 

---