Synthetic equivalents table

If this protocol is applied to disconnect fragments 20 - 23, either carbon at the point of disconnection can be assigned as a donor (d) or an acceptor (a), giving four different possibilities. Disconnect products 20 and 21, for example, become 25 or 26 and 27 or 28, respectively. Fragments 25 - 28 are still not real molecules, and another step is required before the best donor-acceptor pair can be chosen each fragment must be correlated with a synthetic equivalent. Table 1.2 provides a list of common synthetic equivalents, leading to a modified definition of synthetic equivalent, which is a molecular fragment that is equivalent to a real molecule... 

Trifluoroacetamidine (585) is most widely used for the principal synthesis of pyrimidines. Compound 585 can be prepared from ethyl trifluoroacetate by ammo-nolysis, followed by dehydration with P2O5 and reaction with ammonia (Scheme 124) [335,336]. Amidine 585 has been introduced into reaction with various p-dicarbonyl compounds and their synthetic equivalents (Table 27), including p-ketoesters (Entries 1-6), in particular p-ketopyruvates (Entry 3) and a-alkoxymethylene-p-ketoesters (Entries 4-6), p-enaminocarbonyl compounds (Entries 7-9), malonic acid derivatives (Entry 10), fluorinated p-diketones (Entry 11), vinamidinium salts (Entry 12), a,p-unsaturated nitriles with leaving group at p position (Entries 13-15) and other bis-electrophiles (Entries 16, 17). Usually, the reaction gives moderate yields of the target 2-CF3-pyrimidines (ca. 50 %). 

Naturally occurring colored minerals that contain oxides of iron are known by such names as ochre [1309-37-1], umber [12713-03-0], sienna [1309-37-1], etc. These show greater variation in color and tinting power than the synthetic equivalents, and the nature and amount of impurities in the national products is also variable. Most of the pigments identified in Table 9 are, therefore, manufactured synthetically. They are primarily used in skin-makeup products and in eye-area colorants. 

A quite simple way to form the oxazolo[3,4- ]pyridine or thiazolo[3,4- ]pyridine ring system is to build the five-membered ring, respectively, starting from a 2-hydroxymethyl-piperidine or 2-thiomethyl-piperidine. The reaction of the latter compounds with aldehydes, acetals, phosgene, carbonates, or synthetic equivalents have been known for years and will therefore not be detailed here. Representative and typical examples are summarized in Table 10. 

This is currently the only method that allows reversible enhancement of the acidity of a-nitrogen CH-protons in a large variety of secondary amines using the nitroso group on the nitrogen (X = NO, see examples in Table I). The nucleophile 2 is synthetically equivalent to an a-aminocarbanion 4 while the inherent reactivity at carbons next to amino nitrogens is electrophilic (see the immonium ion 5).8,9 Lithiated nitrosamines are also useful because their... 

In the Suzuki reaction, an aryl iodide or synthetic equivalent thereof is coupled with an arylboronic acid or a borane, again using palladium(O) as the catalyst. This reaction is usually used to prepare biaryls, and few examples have been reported of the solid-phase synthesis of alkenes by means of a Suzuki coupling (Table 5.8). 

Ketones can be a-brominated on solid phase by treatment with synthetic equivalents of bromine, such as pyridinium tribromide (Entry 2, Table 6.1) or phenyltri-methylammonium tribromide (DCM, 20 °C, 3 h [10]). Resin-bound organometallic compounds, such as vinylstannanes [11] or organozinc derivatives [12], react cleanly with iodine to yield the corresponding vinyl or alkyl iodides (see also Section 3.13). Additions of halogens or their synthetic equivalents to C=C double bonds on cross-... 

Carbamates have mainly been used in solid-phase synthesis as linkers and protective groups for amines (see Sections 3.6.2 and 10.1.10.1). Carbamates are generally prepared by treating amines with aryl carbonates or chloroformates, which can be prepared from alcohols and phosgene or synthetic equivalents thereof. The alternative route, in which carbamates, isocyanates, or carbamoyl chlorides are reacted with alcohols, is less widely used, but can also lead to satisfactory results on insoluble supports (Tables 14.7 and 14.8). 

The preparation of carbonates is mechanistically closely related to the synthesis of carbamates, and similar reagents can be used for this purpose (Table 14.10). Resin-bound alcohols can be directly converted into carbonates by treatment with a chloro-formate (see Experimental Procedure 14.2), in two steps by activation with phosgene or a synthetic equivalent thereof followed by reaction with an alcohol in the presence of a base, or by treatment of a resin-bound alcohol with carbon dioxide and an alkyl halide under basic reaction conditions [125]. Thiocarbonates can be prepared from... 

TABLE 3. SYNTHETIC EQUIVALENTS (APPROXIMATIONS OR ANALOGUES) OF VARIOUS NATURAL FLAVORS... 

In the last sections, 3-nitro-2-pyridones 28 are synthesized by TCRT of nitropyrimidinone 3 with ketones 22 in the presence of ammonium acetate. The C2 - C3 - C4 unit of 28 is derived from the C4 - C5 - C6 unit of pyrim-idinone 3, which behaves as the synthetic equivalent of a-nitroformylacetic acid 29. The same partial structure is also found in l,3-dinitroquinolizin-4-one 35 [55], which is regarded as the dinitropyridone blocked with a benzene ring on the [/] face [56], and only a single kind of TCRT is expected to proceed. Nitropyridones 28 are actually prepared in moderate yields by TCRT upon treatment of quinolizinone 35 with ketones 22 in the presence of ammonium acetate as the nitrogen source (Table 7) [57]. 

When pyrimidinone 3 is treated with ethyl 3-oxobutanoate 19a in the presence of ammonium acetate, a different type of TCRT proceeds, giving ethyl 4-aminopyridine-3-carboxylate 41a (Table 10) [59]. In this reaction, pyrimidinone 3 behaves as the synthetic equivalent of activated diformylamine 5, and the amino group at the 4-position is derived from ammonium acetate. Since 3-ethoxycarbonyl-4-pyridone 14a prepared in Sect. 5.2 is intact under the same conditions, aminopyridine 41a is not formed via pyridone 14a. Furthermore, ammonium ion also causes no change on ethyl 3-oxobutanoate 19a, which indicates enamine is not dinucleophilic reagent in the present reaction. Hence, the keto ester moiety is converted to the enaminone after the addition of 19a to pyrimidinone 3. 

The most widely used method for the preparation of 1,3,2-dioxathiolane. Y-oxides (cyclic sulfites) 65 bearing C-linked substituents is the reaction of the corresponding 1,2-diols with thionyl chloride in presence of pyridine or Et3N (Scheme 18). More reactive 1,3,2-dioxathiolane. Y,.Y-dioxidcs (cyclic sulfates) 66 are usually obtained by oxidation of sulfites 65 with sodium periodate, which is mediated by mthenium tetroxide generated in situ from a catalytic amount of ruthenium trichloride. Numerous derivatives 65 and 66 were obtained via this approach and its modifications for further transformations, mostly as the synthetic equivalents of epoxides <1997AHC89, 2000T7051> (see also Sections 6.05.5 and 6.05.6, and Tables 1-7). 

Dioxathiolane. Y-oxidcs (cyclic sulfites) and 1,3,2-dioxathiolane. Y,.Y-dioxides (cyclic sulfates) have been widely used in organic chemistry, mostly as the synthetic equivalents of epoxides (Sections 6.05.5 and 6.05.6 Tables 1-7). 

Reductive cleavage and hydrolysis of appropriate diisoxazolylmethanes leads to 1,3,5,7-tetraketones, which can be used in the biomimetic synthesis of benzenoid compounds, which are formed in nature by the polyketide pathway. Some of these results are summarized in Table VIII. The synthesis of compounds such as (97) has provided a synthetic equivalent of a 1,3,5,7,9-... 

Table 8. Optimum Reported Diastereoselectivities in the Epoxidation of Simple Acyclic Allylic Alcohols and Their Silylated Synthetic Equivalents...

Heterolytic retrosynthetic disconnection of a carbon-carbon bond in a molecule breaks the TM into an acceptor synthon, a carbocation, and a donor synthon, a carbanion. In a formal sense, the reverse reaction — the formation of a C-C bond — then involves the union of an electrophilic acceptor synthon and a nucleophilic donor synthon. Tables 1.1 and 1.2 show some important acceptor and donor synthons and their synthetic equivalents. "... 

Hetero-Diels-Alder reactions of l-oxa-l,3-butadienes with vinyl ethers, which lead to 3,4-dihydro-2H-pyran derivatives, are synthetically equivalent to Michael type conjugate additions. Wada and coworkers presented the first examples of a catalytic asymmetric intermolecular hetero-Diels-Alder reaction by the use of ( )-2-oxo-l-phenylsulfonyl-3-alkenes 25 and vinyl ethers 26 (Table 3) [25]. 

Modem synthetic practice frequently requires the use of methods mote specific than those outlined above. Much attention has been focused on the mixed Claisen or Dieckmann reaction, i.e. the acylation of one ester by another, or its intramolecular equivalent, the regioselective cyclization of an unsymmetri-cal diester. A similar problem arises with the acylation of unsymmetrical ketones. This chapter thus describes the inter- and intra-molecular carbon-carbon bond-forming reactions in which a delocalized enolate anion (or close equivalent) reacts at an sp carbon atom in an addition-elimination sequence, as well as the acid-catalyzed equivalent employing an enol. In Table 1 we list the potential nucleophiles and the electrophiles that have been employed in these reactions, although not every possible combination has been reduced to synthetic practice. Table 2 gives details of acid-catalyzed acylations (see Section 3.6.4.3). 

Sharpless and Kim reported a one-pot synthesis of cyclic sulfates 96 from 1,2-diols via catalytic oxidation with ruthenium chloride51. The cyclic sulfates 96 thus formed on treatment with nucleophiles give /2-sulfates 97, which in turn are hydrolyzed to the / -hydroxy compounds 98 (equation 54). Hence the cyclic sulfates 96 are synthetically equivalent to epoxides. The results of ring opening of cyclic sulfates 96 are shown in Table 4. When the reaction of 99 with malonate anion is carried out in DME, the /2-sulfate moiety serves as a leaving group to give cyclopropane 100 (equation 55)51. 

Table 1.2. Common synthetic equivalents for disconnect products...

For disconnect fragments 22 and 23 in Section 1.2, convert each to a real molecule using synthetic equivalents in Table 1.2. Briefly discuss the retrosynthetic and synthetic sequences and show the complete retrosynthetic analysis based on this disconnection. 

In the lithiated dicarbamate 111 of (S)-2-(dibenzylamino)-l,4-butanediol (derived from L-aspartic acid) the 4-carbamoyloxy group also possesses a high tendency for intramolecular complexation [Eq. (31)] [75, 76]. The favorable equatorial positions of the dibenzylamino and 1-carbamate groups are displayed in the transition state of the deprotonation. When treated with sec-butyl-lithium in ether or THE, the bicyclic chelate complex 111 is formed exclusively by removal of the pro-S-IH atom. Trapping of 111 by many types of electrophiles gives stereohomogeneous substitution products 112 [Eq. (31), Table 3]. Since deprotection proceeds easily by the usual means, anion 111 constitutes a synthetic equivalent of the synthon 114. No deprotonation in the 4-position was detected, however this can be achieved by protecting the pro-S-lH by conversion to deuterium (see below and Sect. 2.5). 

Bromo-2-pyrone. Based on literature precedent and also on the C NMR chemical shift data in Table 1, our expectation was that 3-bromo-2-pyrone (55) would be unexciting as a diene in Diels-Alder reactions. We were pleasantly surprised to find that pyrone 55 undergoes [4+2] cycloadditions with both electron-rich and electron-poor dienophiles under relatively mild reaction conditions. It has the additional advantage of being considerably more stable than 2-pyrone. The bicyclic lactone adducts formed typically undergo reductive debromination, therefore making 3-bromo-2-pyrone a synthetic equivalent of 2-pyrone. 

While silyl enol ethers 21 and 23 were subjected to similar reaction conditions (Tables 1.5 and 1.6), the allylic C—H bond could also be functionalized by metal carbenoids to afford silyl-protected 1,5-dicarbonyls 22 and 24 respectively, which can be viewed as an equivalent of an asymmetric Michael reaction. Although the double bond is highly electron-rich and readily undergoes cyclopropanation in the presence of most other metal carbenoids, by using aryldiazoacetates 1 as carbene precursors, cyclic silyl enol ethers 21 were readily transformed into their corresponding allylic C—H bond insertion products 22 (22 ) in excellent yields, excellent ee and moderate de (Table 1.5). Noticeably, while acyclic silyl enol ethers 23 were subjected to the reaction, excellent diastereoselectivity (>90% de) was obtained, which shows great potential in synthetic applications (Table 1.6). 

The reaction was successfully applied to both electron-rich and electron-poor 4-nitrophenyl carboxylates among them, the conversion of the electron-deficient esters was found to be faster and more efficient. Many functional groups are tolerated on both the side of the carboxylic ester (halo, keto, formyl, ester, cyano, nitro and protected amino groups, heterocyclic and a,-unsaturated carboxylic esters) and of the alkene (electron-rich alkyl-substituted alkenes, electron-poor acrylate derivatives, trimethylvinylsilane as an ethylene surrogate). The cinnamate derivatives could become particularly useful substrates, since the availability of the synthetically equivalent vinyl halides is rather limited. In analogy to conventional Mizoroki-Heck chemistry, linear (Zi)-substituted alkenes are predominantly but not exclusively obtained. Selected examples are shown in Table 4.1. 

The xanthans were obtained from four commercial manufacturers. The products are denoted Xanthan A, B, C and D. Xanthans A, B and C were sup-plied as the gelatinous crude fermentation broths containing 3-8 wt% xanthan. Xanthan D was supplied as a powder. Six different production lots of Xanthan A were examined, and these polymers are labeled as A-l,...A-6. The compositions of the two test brines are presented in Table 1. Brine 1 was a moderate-salinity brine containing only NaCl and CaCl2. Brine 2 was the synthetic equivalent of the resident brine in one of Exxon s reservoirs. 

Consideration of quahtatively similar cross-coupling reactivity allows an extension of the Kumada-Corriu reaction to sulfonamide leaving groups and provides yet another 1,2-dipole synthetic equivalent (Scheme 14.15, Table 14.12). Successful... 

The ether is prepared via the corresponding halide. If the C-0 bond in 163 is disconnected, the logical bond polarization makes O 6- and a donor site Cj, and that of C2 is 6+, or (an acceptor site). In Chapter 25, Table 25.1 indicates that a synthetic equivalent for Cg is an alkyl halide. Therefore, a reasonable disconnection of 163 leads to 2-bromopentane (167) and the nucleophilic methoxide ion. This suggests a Williamson ether synthesis (Section 11.3.2). Can 167 be prepared directly from 1-pentene The answer is yes, by reaction of the alkene with HBr (Chapter 10, Section 10.2). Therefore, the retrosynthesis shown leads to the synthesis shown in which 1-pentene reacts with HBr to give 167, and a subsequent Sn2 reaction with... 

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