Application of the Sequencer

Diastereomers include all stereoisomers that are not related as an object and its mirror image. Consider the four structures in Fig. 2.3. These structures represent fee four stereoisomers of 2,3,4-trihydroxybutanal. The configurations of C-2 and C-3 are indicated. Each stereogenic center is designated J or 5 by application of the sequence rule. Each of the four structures is stereoisomeric wife respect to any of fee others. The 2R R and 25,35 isomers are enantiomeric, as are fee 2R, iS and 25,3J pair. The 21 ,35 isomer is diastereomeric wife fee 25,35 and 2R,3R isomers because they are stereoisomers but not enantiomers. Any given structure can have only one enantiomer. All other stereoisomers of feat molecule are diastereomeric. The relative configuration of diastereomeric molecules is fiequently specified using fee terms syn and anti. The molecules are represented as extended chains. Diastereomers wife substituents on the same side of the extended chain are syn stereoisomers, whereas those wife substituents on opposite sides are anti stereoisomers. 

A similar series of reactions was performed by Paulsen and Hdlck141 for the preparation of the T-antigenic, unprotected, amino acid-disaccha-rides 200 and 201, starting from the 4,6-0-benzylidene-N-(benzyloxy-carbonyl) benzyl esters 198 and 199, respectively, by condensation with 110 in the presence of mercury dicyanide-mercury dichloride and molecular sieves 4A, and deprotection of the product. Sinay and co-workers148 also reported the synthesis of hexa-O-acetyl derivatives of 200 and 201 by application of the sequence of azido-nitration-bromination. 

Hanson, K. R. Applications of the sequence rule. I. Naming the paired ligands g,g at a tetrahedral atom Xggij. II. Naming the two faces of a trigonal atom Yghi. J. Am. Chem. Soc. 88, 2731-2742 (1966). 

The cydoaddition of buta-1,3-diene (11) to tetrahalogenocyclopropenes, as developed originally by Tobey, provides convenient access to tetrahalogenobicy-clo[3.1.0]hept-2-enes, which undergo bis-(hydro,chloro) elimination by treatment with a base. This simple scheme was first exploited by Vogel et al. in their synthesis of 1,1-difluorobenzocyclopropene (21) from 11 and 1,2-dibromo-3,3-difluorocy-clopropene (19) via 20. Subsequent applications of the sequence used the more readily available l,2-dichloro-3,3-difluorocyclopropene instead of 19. ° ... 

A pseudochirality centre exists on a tetrahedrally coordinated atom when two of the substituents are constitutionally identical but have the opposite chirality sense, i.e. they are enantiomorphic. An R-configured group has priority over an S-configured group. Thus it is possible to determine the configuration of a pseudo chirality centre by application of the sequence rules. To distinguish a pseudo chirality centre from a chirality centre the stereodescriptors r and s are used. 

Carbohydrates. Here the application of the sequence rules to the many -CH(OH)- groups is possible but tedious and confusing. Carbohydrates retain the system based on assigning the key chiral centre to the d- or l- series, as described in Chapter 5. 

Beckmann rearrangement to ethyl 5-cyano-2-oximinovalerate. Hydrogenation over Raney nickel and a basic co-catalyst and hydrolysis afforded DL-lysine monohydrochloride in 63% overall yield from cyclohexanone. A less fully studied application of the sequence to cyclopentanone affords DL-ornithine in overall yield of 21%. W. H. Hartung and F. Crossley, Org. Syn., Coll. Vol.,2.363 (1943)... 

Closely related to the measurement of HMQC spectra of I S , spin systems is the indirect detection of quadrupolar nuclei. While the standard HMQC sequence of Fig. 3(c) proved feasible for indirect detection of spin-3/2 nuclei such as "B and Ni, a theoretical analysis of the behaviour of spin systems with I(S) = 1 led to suggest a modified HMQC scheme (Fig. 4(a)) for systems with a single spin-1 S nucleus. Deviations from the standard scheme include the use of a shorter defocusing delay (4 /(I,S)) and of an additional 90°(I) pulse prior to t,. Application of the sequence was demonstrated for the case of a C D spin system. In addition, it was shown that correlation spectra of I Sm spin systems with different numbers of spin-1 S-nuclei can be obtained with an HSQC sequence, albeit by paying the price that the correlation signals appear at twice their real chemical shift in FI. 

There are many synthetically useful conversion reactions of a,p-unsaturated nitriles to a,p-unsaturated aldehydes using DIBAL-H. To illustrate the value of the method, we have brought together all the examples concerned with chemistry of retinal. Thus, the applicability of the sequence combining the use of diethyl cyanomethylphosphonate with diethyl 3-cyano-2-methyl-2-prope-nylphosphonate, diethyl 3-cyano-2-butenylphosphonate, or diethyl 3-cyano-2-methyl-l-ethyl-2-propenylphosphonate has been studied intensively in retinal synthesis to prepare retinal analogues ... 

Application of the sequence to vinyllithium results in the Markovnikov secondary alcohol (10) ... 

Rg. 2.16 The pulse sequence used to determine spectra under dipolar decoupling conditions. Note that only the envelope curve of the FID is shown, not the high-frequency oscillations within it. This is what is usually recorded Fourier analysis then yields the spectrum as frequency shifts from the irradiating frequency. For all pulse sequences, the recovery time Tr between repeated applications of the sequence must be long compared with T. (Adapted from Nuclear Magnetic Resonance in Solid Polymers by V. J. McBrierty and K. J. Packer. Cambridge University Press, 1993.)... 

When the chiral center is tricoordinate, as in the case of optically active sulfoxides, sulfonium salts, and phosphines, then a phantom atom of atomic number zero is assumed to occupy the fourth site of the presumed tetrahedron. Application of the sequence rules in the usual manner yields R as the configuration of (+)-benzyl p-tolyl sulfoxide, and 5 as the configuration of (+)-phenyl-ethylmethylphosphine, the structures of which have been presented previously (see p. 41). 

The specification of the configuration of diastereomers is done by a direct extension of the sequence rule. Each chiral center is designated Rot Shy application of the sequence rule. The structures in Fig. 2.3 can serve as examples for study. 

Second, among the newer methods developed to effect the elimination to produce the least substituted alkene is one that involves converting the alcohol to a selenium derivative. In this procedure, a primary alcohol is treated with o-nitrophenyl sele-nocyanate in a suitable solvent such as (THF, oxacyclopentane) in the presence of a phosphine (such as tri-n-butylphosphine [(CH3CH2CH2CH2)3P]) to produce the primary alkyl selenide (Scheme 8.74). Then, in a second step, the primary alkyl o-nitrophenyl selenide is oxidized with hydrogen peroxide to yield the corresponding selenoxide, which readily undergoes elimination to the alkene. Scheme 8.74 shows the application of the sequence of reactions described above to cyclohexylmethanol and the resulting formation of the exo-methylenecyclohexane. 

Hanson, K. R. "Applications of the Sequence Rule. 1. Naming the Paired Ligands g,g at the Tetrahedral Atom Xggij. 11. Naming the Two Faces of a Trigonal Atom Yghi." /. Am. Chem. Soc., 88,2731 (1996). 

Now, let us calculate the application of the sequence jTgjTiJT jTgjT-] over these states, noticing that each pulse in the sequence simply inverts the population of the respective transition, and that the states 000>, 001), 010> and 011> remain unaffected ... 

Application of the sequence rules gives as the priorities NH2, CH2SH, CO2H, H. The mercaptomethyl substituent is of higher priority than the carboxyl group... 

For the morphological discussions, NMR measurements must be carried out in the solid state. The cross-polarization and magic angle sample spinning (CPMAS) for and the solid echo pulse sequence for are practical methods. From CPMAS measurements, the spectrum similar to the solution NMR spectrum is observed. NMR chemical shifts are easily obtained from the CPMAS spectrum. Furthermore, the application of the sequence developed by Torchia supplies Tj in the solid state. However, C NMR measurements are time consuming because of the low natural abundance of C nucleus. Tj of H can be observed easily by the solid echo... 

The total synthesis of alkaloid (+)-lycoricidine reported by Yadav et al. represents a further application of the sequence domino reductive fragmentation/allylation followed by ring-closing metathesis in the synthesis of bioactive natural products [42], Thus, reaction of co-iodoglycoside 29 with zinc/allyl bromide in THF/HjO afforded diene 30 (87%, dr 85 15). Ring-closing metathesis of diene 30 followed by acetylation furnished cyclohexene 31. Treatment of the acetate 31 with PhINTs in the presence of Cu(acac)2, followed by sodium naphthalenide, afforded the aziridine 32 (67%), from which (-i-)-lycoricidine (33) can be easily obtained (Scheme 3.11). 

---