Synthesis of thermodynamically stable

Fig. 21 Thermodynamic resolution of (M/P)-42 with (i, i )-diaminocyclohexane 43 (top) and the synthesis of thermodynamically stable nanocube 45 (bottom).133 Reprinted with permission from Ref.113 (For color version of this figure, the reader is referred to the web version of this book.)...

A particularly elegant application of DERA is the sequential synthesis of thermodynamically stable cyclic hemiacetal. Two DERA-catalyzed aldol reactions convert one equivalent of acceptor and two equivalents of acetaldehyde into this stable compound. A mild subsequent oxidation yielded the corresponding lactone in ex-... 

A report of the synthesis of thermodynamically stable ( )-vinylphosphonates from diethyl 1-formyl-l-phenylalkylphosphonates by a Homer-Wadswoilh-Ermnons-type reaction has appeared. Sodium P-hydroxyphosphonates, generated by the reaction of sodium dialkyl phosphites with... 

Synthesis of Thermodynamically Stable Zeolites in the Na20-Al203-Si02-H20 System... 

Several years ago in our research laboratories, a novel route to the synthesis of kinetically stable rotaxane-like19121 spedes was discovered,1131 which relies upon the aforementioned balance between kinetics and thermodynamics. This route is termed slippage inasmuch as the rotaxane-like species are obtained when a preformed macrocycle bears a cav-... 

Nb and Ta derivatives are hard acids and then-complexes with P- or As-donors are limited. Tertiary phosphines, especially PMes, have been widely used to stabilize low-valent derivatives. C-H activation reactions, promoted by the formation of thermodynamically stable Ta-H, Ta-C, and Ta=C bonds have resulted in metallacycles based on unusual anionic phosphorus donors. Nucleophilic Ta phosphinidene complexes could be stabilized by a tripodal tetradentate [NN3] amido ligand. The terminal PR ligand reacts smoothly with aldehydes, providing a general synthesis of phosphaalkenes RP=C(H)R and act thus as a phospha-Wittig reactant see Phosphorus Organophosphorus Chemistry). 

Vinyl cations [1], the dicoordinated unsaturated analogs of divalent carbenium ions, were first detected by Grob and coworkers in the early 1960s in solvolysis reactions of a-aryl vinyl halides [2]. The direct NMR detection of vinyl cations in superacidic media was achieved in 1992 at temperatures below -100 °C [3]. We recently reported a convenient synthesis of unusually stable vinyl cations at room temperature [4, 5]. One reason for the unusual high thermodynamic stabilization of these vinyl cations is the presence of two 3-silyl substituents. [4]. We report here details of the X-ray structure of the vinyl cation 1 and discuss the structural and spectroscopic consequences of 3-SiC hyperconjugation [6]. 

TiCU-mediated Prins cyclization of S, - and unsaturated ketones offers a simple stereoselective annulation method for construction of thermodynamically stable, tertiary cyclohexanols with incorporation of a cis-chloro substituent [327] (Scheme 14.144). This reaction showed the potential usefulness in the synthesis of halogenated terpenes or some other types of functionalized cyclohexanols. 

An interesting case are the a,/i-unsaturated ketones, which form carbanions, in which the negative charge is delocalized in a 5-centre-6-electron system. Alkylation, however, only occurs at the central, most nucleophilic position. This regioselectivity has been utilized by Woodward (R.B. Woodward, 1957 B.F. Mundy, 1972) in the synthesis of 4-dialkylated steroids. This reaction has been carried out at high temperature in a protic solvent. Therefore it yields the product, which is formed from the most stable anion (thermodynamic control). In conjugated enones a proton adjacent to the carbonyl group, however, is removed much faster than a y-proton. If the same alkylation, therefore, is carried out in an aprotic solvent, which does not catalyze tautomerizations, and if the temperature is kept low, the steroid is mono- or dimethylated at C-2 in comparable yield (L. Nedelec, 1974). 

Catalytic hydrogenation of the 14—15 double bond from the face opposite to the C18 substituent yields (196). Compound (196) contains the natural steroid stereochemistry around the D-ring. A metal-ammonia reduction of (196) forms the most stable product (197) thermodynamically. When R is equal to methyl, this process comprises an efficient total synthesis of estradiol methyl ester. Birch reduction of the A-ring of (197) followed by acid hydrolysis of the resultant enol ether allows access into the 19-norsteroids (198) (204). 

The synthesis of isoxazolines usually takes the most thermodynamically favorable course to yield solely the more stable isomer. However, cinnamic acids (38) give not only isoxazoline-4-carboxylic acids (39) but also, as a by-product, the less stable isoxazoline-5-carboxylic acids (40)" which on heating undergo retro-addition. ... 

A cursory inspection of key intermediate 8 (see Scheme 1) reveals that it possesses both vicinal and remote stereochemical relationships. To cope with the stereochemical challenge posed by this intermediate and to enhance overall efficiency, a convergent approach featuring the union of optically active intermediates 18 and 19 was adopted. Scheme 5a illustrates the synthesis of intermediate 18. Thus, oxidative cleavage of the trisubstituted olefin of (/ )-citronellic acid benzyl ester (28) with ozone, followed by oxidative workup with Jones reagent, affords a carboxylic acid which can be oxidatively decarboxylated to 29 with lead tetraacetate and copper(n) acetate. Saponification of the benzyl ester in 29 with potassium hydroxide provides an unsaturated carboxylic acid which undergoes smooth conversion to trans iodolactone 30 on treatment with iodine in acetonitrile at -15 °C (89% yield from 29).24 The diastereoselectivity of the thermodynamically controlled iodolacto-nization reaction is approximately 20 1 in favor of the more stable trans iodolactone 30. 

The intramolecular Michael addition11 of a nucleophilic oxygen to an a,/ -unsaturated ester constitutes an attractive alternative strategy for the synthesis of the pyran nucleus, a strategy that could conceivably be applied to the brevetoxin problem (see Scheme 2). For example, treatment of hydroxy a,/ -unsaturated ester 9 with sodium hydride furnishes an alkoxide ion that induces ring formation by attacking the electrophilic //-carbon of the unsaturated ester moiety. This base-induced intramolecular Michael addition reaction is a reversible process, and it ultimately affords the thermodynamically most stable product 10 (92% yield). 

As described in Section 2.3.2, vinylaziridines are versatile intermediates for the stereoselective synthesis of (E)-alkene dipeptide isosteres. One of the simplest methods for the synthesis of alkene isosteres such as 242 and 243 via aziridine derivatives of type 240 and 241 (Scheme 2.59) involves the use of chiral anti- and syn-amino alcohols 238 and 239, synthesizable in turn from various chiral amino aldehydes 237. However, when a chiral N-protected amino aldehyde derived from a natural ot-amino acid is treated with an organometallic reagent such as vinylmag-nesium bromide, a mixture of anti- and syn-amino alcohols 238 and 239 is always obtained. Highly stereoselective syntheses of either anti- or syn-amino alcohols 238 or 239, and hence 2,3-trans- or 2,3-as-3-alkyl-2-vinylaziridines 240 or 241, from readily available amino aldehydes 237 had thus hitherto been difficult. Ibuka and coworkers overcame this difficulty by developing an extremely useful epimerization of vinylaziridines. Palladium(0)-catalyzed reactions of 2,3-trons-2-vinylaziri-dines 240 afforded the thermodynamically more stable 2,3-cis isomers 241 predominantly over 240 (241 240 >94 6) through 7i-allylpalladium intermediates, in accordance with ab initio calculations [29]. This epimerization allowed a highly stereoselective synthesis of (E) -alkene dipeptide isosteres 243 with the desired L,L-... 

Vinylindoles have been studied extensively and used in the synthesis of carbazoles, alkaloids and other classes of pharmacologically active compounds. MMX force field calculations have shown that coplanar s-cis and. s-trans conformations of 3-vinylindole (84, Figure 2.11) are the most stable conformers they exhibit only slight differences in their thermodynamic stabilities [86]. 

The synthesis of confound 16 was reported. Valence isomerisation of 16 to the isoannulenofuran 17 could be achieved either photochemically or thermally with 16 as the thermodynamically more stable isomer <96JOC935>. 

In 1995, and regrettably missed in last year s review, Klotgen and Wiirthwein described the formation of the 4,5-dihydroazepine derivatives 2 by lithium induced cyclisation of the triene 1, followed by acylation <95TL7065>. This work has now been extended to the preparation of a number of l-acyl-2,3-dihydroazepines 4 from 3 <96T14801>. The formation of the intermediate anion and its subsequent cyclisation was followed by NMR spectroscopy and the stereochemistry of the final product elucidated by x-ray spectroscopy. The synthesis of optically active 2//-azepines 6 from amino acids has been described <96T10883>. The key step is the cyclisation of the amino acid derived alkene 5 with TFA. These azepines isomerise to the thermodynamically more stable 3//-azepines 7 in solution. 

There are very few examples of asymmetric synthesis using optically pure ions as chiral-inducing agents for the control of the configuration at the metal center. Chiral anions for such an apphcation have recently been reviewed by Lacour [19]. For example, the chiral enantiomerically pure Trisphat anion was successfully used for the stereoselective synthesis of tris-diimine-Fe(ll) complex, made configurationally stable because of the presence of a tetradentate bis(l,10-phenanthroline) ligand (Fig. 9) [29]. Excellent diastereoselectivity (>20 1) was demonstrated as a consequence of the preferred homochiral association of the anion and the iron(ll) complex and evidence for a thermodynamic control of the selectivity was obtained. The two diastereoisomers can be efficiently separated by ion-pair chromatography on silica gel plates with excellent yields. 

The new phases were discovered by the combination of exploratory synthesis and a phase compatibility study. As commonly practised, the new studies were initially made through the chemical modification of a known phase. Inclusion of salt in some cases is incidental, and the formation of mixed-framework structures can be considered a result of phase segregation (for the lack of a better term) between chemically dissimilar covalent oxide lattices and space-filling, charge-compensating salts. Limited-phase compatibility studies were performed around the region where thermodynamically stable phases were discovered. Thus far, we have enjoyed much success in isolating new salt-inclusion solids via exploratory synthesis. 

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