Synthesis from Cyclic Precursors

Addition reactions of thiopyrylium salts with nucleophiles (83AHC145, Section IV,B) have widely been used for the preparation of various thiopyrans in the last decade (92MI3). On the other hand, the application of catalytic processes still seems to be rare. 

Two principle approaches from thiopyrylium salts to thiopyrans accompanied by C-substitution have been found, e.g., the one-step additions of C-nucleophiles or the two-step procedures involving primary conversions of the salts to nucleophilic intermediates followed by attacks with appropriate electrophiles. 

A general preparation of 2-acetonyl-2,4,6-triaryl-2//-thiopyrans 58 was discovered in the reaction of corresponding 2,4,6-triarylthiopyrylium perchlorates with ethanolic acetone catalyzed with various dialkylammonium salts (86GEP235455, 86JPR573). This preparative procedure was successfully extended to cyclohexane- and cyclopentane- 1,2-diones as the carbonyl components (89JPR853 90GEP280324). The action of bases on thiopyrylium salts may caused their dimerization to thiopyranyl derivatives under suitable conditions (89KGS479). 

The second approach has been applied in two versions. The chemical version (85CLU19) consists in the lithiation of mixture 54d and 55d, 

with lithium diisopropylamide (LDA) to a lithiospecies and in its subsequent reaction with C02 affording via the corresponding 4-carboxylic acid its ethyl ester 59. In the alternative version perchlorate 48e is electro-chemically reduced in acetonitrile to an anionic species that was converted either to a 3 1 mixture of isomers 56 (R = f-Bu) and 60 or to 4//-thiopyran 56 (R = PhCH2) with f-BuI or PhCH2Br, respectively (90ACS524). The kinetics of the benzylation procedure was followed by cyclic voltammetry [88ACS(B)269]. 

This widely used approach to pyrans has been applied frequently in the last decade. In addition to the preceding article [83AHC(34)145], other reviews involving the conversions of pyrylium salts are available [82AHC(3)140 92MOCH755]. Although most of those transformations are nucleophilic additions, some may be of a radical nature. 

6-Disubstituted pyrylium perchlorates could be successfully reduced to 4//-pyrans 92 (R = Ph, 4-MeOC6H4 R = H) with some tertiary amines (81JHC1235) see Section IV.A.4. 

The conditions of the equilibrium between 95 and % (X = BF4, C104 R toR5 = H, alkyls, aryls) including their thermodynamic interpretation have been established, and the structures of the radicals 95 proved by spectroscopic—mainly ESR—experiments (86NJC345 89BCJ2279 89RCI57). 

A new UV-photochemical method permitting the reduction of perchlorate 99a to 2,6-diphenyl-4//-pyran by a hydride-like transfer from other 4-alkyl-2,6-diphenyl-47/-pyrans has been reported (93T3793). 

Conversion of pyrylium salts with organolithium and Grignard reagents to pyrans via reductive alkylation or arylation has been enriched by applications of organocopper and other organometallic compounds as well as by photochemical activation. Several new studies with anions of C-acids have been published as well. 

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R Dreher, K Poralla, WA Konig. Synthesis of w-alicyclic fatty acids from cyclic precursors by Bacillus subtilis. J Bacteriol 127 1136-1140, 1976. 

Fragmentation reactions may be used to prepare cyclic or acyclic alkenes from cyclic precursors. The stereochemistry of the alkene can be set up by controlling the relative stereochemistry of the cyclic substrate, a process that is normally relatively easy. The ketone 35, for example, an intermediate in a synthesis of juvenile hormone, was obtained stereospecifically from the bicyclic compound 33 using two successive... 

The preparation of acyclic molecules from cyclic precursors is a well-known strategy. The ability to control relative stereochemistry and regiochemistry in the reactions of cyclic molecules is important since cleavage of that ring transfers the resident stereochemistry and/or regiochemistry to the acyclic product Several methods will be described in this chapter that lead to the synthesis of amino acids, particularly substituted amino acids, from various cyclic precursors. 

Aroma chemicals are specific molecules of particular aroma, which can be obtained (I) by isolation from natural sources, with or without chemical modifications, using natural molecules as precursors for many aroma chemicals (partial synthesis) (2) from petrochemical raw materials or (3) by synthesis from cyclic and aromatic precursors. 

Structural drawings of carbohydrates of this type are called Haworth formulas, after the British chemist Sir Walter Norman Haworth (St Andrew s University and the University of Birmingham) Early m his career Haworth contributed to the discovery that carbohydrates exist as cyclic hemiacetals rather than m open chain forms Later he col laborated on an efficient synthesis of vitamin C from carbohydrate precursors This was the first chemical synthesis of a vitamin and provided an inexpensive route to its prepa ration on a commercial scale Haworth was a corecipient of the Nobel Prize for chem istry m 1937... 

The synthesis of new heterocyclic derivatives under conservation of a preformed cyclic structure is not only of particular importance for the synthesis of ionic 1,3,2-diazaphosphole or NHP derivatives but has also been widely apphed to prepare neutral species with reactive functional substituents. The reactions in question can be formally classified as 1,2-addition or elimination reactions involving mutual interconversion between 1,3,2-diazaphospholes and NHP, and substitution processes. We will look at the latter in a rather general way and include, beside genuine group replacement processes, transformations that involve merely abstraction of a substituent and allow one to access cationic or anionic heterocycle derivatives from neutral precursors. 

The reaction of ADC compounds with carbenes and their precursors has already been discussed in Section IV,A- In general, the heterocyclic products are not the result of 1,2-addition but of 1,4-addition of the carbene to the —N=N—C=0 system.1 Thus the ADC compound reacts as a 4n unit in a cheletropic reaction leading to the formation of 1,3,4-oxadiazolines. Recent applications include the preparation of spiro-1,3,4-oxadiazolines from cyclic diazoketones and DEAZD as shown in Eq. (14),133 and the synthesis of the acyl derivatives 85 from the pyridinium salts 86.134 The acyl derivatives 85 are readily converted into a-hydroxyketones by a sequence of hydrolysis and reduction reactions. 

The photolysis of carboxylic acids and derivatives as lactones, esters and anhydrides can yield decarboxylated products 253>. This reaction has been utilized in the synthesis of a-lactones from cyclic diacyl peroxides 254) (2.34) and in the synthesis of [2,2]paracyclophane by bis-decarboxylation of a lactone precursor (2.35) 255). This latter product was also obtained by photoinduced desulfurization of the analogous cyclic sulfide in the presence of triethyl phosphite 256). 

The same group has exploited this interesting dehydrogenase for the synthesis of cyclic amino acids from linear precursors by developing a one-pot, two-enzyme system (Scheme 2.16). t-Lysine oxidase or L- or d-AAO were initially used to... 

Total synthesis of carbohydrates (in enantiomeric forms) can be roughly divided into two large areas syntheses starting from aliphatic precursors and those employing cyclic substrates. 

The epoxy alcohol 47 is a squalene oxide analog that has been used to examine substrate specificity in enzymatic cyclizations by baker s yeast [85], The epoxy alcohol 48 provided an optically active intermediate used in the synthesis of 3,6-epoxyauraptene and marmine [86], and epoxy alcohol 49 served as an intermediate in the synthesis of the antibiotic virantmycin [87], In the synthesis of the three stilbene oxides 50, 51, and 52, the presence of an o-chloro group in the 2-phenyl ring resulted in a lower enantiomeric purity (70% ee) when compared with the analogs without this chlorine substituent [88a]. The very efficient (80% yield, 96% ee) formation of 52a by asymmetric epoxidation of the allylic alcohol precursor offers a synthetic entry to optically active 11 -deoxyanthracyclinones [88b], whereas epoxy alcohol 52b is one of several examples of asymmetric epoxidation used in the synthesis of brevitoxin precursors [88c]. Diastereomeric epoxy alcohols 54 and 55 are obtained in combined 90% yield (>95% ee each) from epoxidation of the racemic alcohol 53 [89], Diastereomeric epoxy alcohols, 57 and 58, also are obtained with high enantiomeric purity in the epoxidation of 56 [44]. The epoxy alcohol obtained from substrate 59 undergoes further intramolecular cyclization with stereospecific formation of the cyclic ether 60 [90]. 

Nevertheless 1,3 dipolar cycloadditions are an important method for the synthesis of a wide variety of heterocyclic compounds. Furthermore they illustrate the generality of 4 + 2 cycloaddition reactions as a means to prepare cyclic products efficiently from acyclic precursors. 

Acetylpyrroles such as 17 have also been prepared via cyclization of the enamines 18, which were in turn readily prepared from the corresponding dimethylaminoalkene 19 by displacement of the dimethylamino group by amino acids. When applied to cyclic precursors, the approach also proved to be useful for the synthesis of fused pyrroles <02JCS(P1)2799>. 

The application of 3-amino-2//-azirines as amino acid equivalents and their use in the synthesis of cyclic dipeptides presumably includes ring enlargement steps [14]. The formation of 12- or 15-membered cyclodepsipeptides from open chain precursors possibly includes ring enlargement steps [3] [15]. 

It is worth mentioning the synthesis of cyclic a-methylene carbamates, which were also produced via Markovnikov intramolecular nucleophilic addition of O-car-bamates, generated in situ from a propargylic amine and CO2, in the presence of Ru(cod) (cot)/phosphine as catalyst precursor (cod cyclooctadiene cot cycloocta-triene) (Scheme 8.23) [75]. 

There are also special procedures which allow the preparation of sugars with only endo- or only exo-cyclic double bonds. The first group of compounds with endo-cyclic double bond may be prepared by total synthesis from non-carbohydrate precursors. The particularly useful hetero Diels-Alder reaction (O Fig. 3) allows one to obtain the dihydropyran skeleton either by reaction of a diene with a heterodienophile [3,17] or by reaction of a heterodiene with a normal dienophile [18]. 

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