Amines stereochemistry

Molybdenum, tetrakis(l-adamantoxo)(dimethy]amine)-stereochemistry, 1, 44... 

This alkylation strategy has been successfully implemented to the diastereoselective synthesis of a number of biologically active compounds,17 19 32 72 73 including the orally active HIV protease inhibitor Crixivan (>95% de)17-19 and nucleoside antibiotic (+)-sinefungin (51) (>99% de).72 The C-6 amine stereochemistry of (+)-sinefungin was set by a highly diastereoselective allylation of (lS,2/ )-l-amino-2-indanol-derived oxazolidinone 52 (Scheme 24.10). 

Based on the above-mentioned stereochemistry of the allylation reactions, nucleophiles have been classified into Nu (overall retention group) and Nu (overall inversion group) by the following experiments with the cyclic exo- and ent/n-acetales 12 and 13[25], No Pd-catalyzed reaction takes place with the exo-allylic acetate 12, because attack of Pd(0) from the rear side to form Tr-allyl-palladium is sterically difficult. On the other hand, smooth 7r-allylpalladium complex formation should take place with the endo-sWyWc acetate 13. The Nu -type nucleophiles must attack the 7r-allylic ligand from the endo side 14, namely tram to the exo-oriented Pd, but this is difficult. On the other hand, the attack of the Nu -type nucleophiles is directed to the Pd. and subsequent reductive elimination affords the exo products 15. Thus the allylation reaction of 13 takes place with the Nu nucleophiles (PhZnCl, formate, indenide anion) and no reaction with Nu nucleophiles (malonate. secondary amines, LiP(S)Ph2, cyclopentadienide anion). 

Allylic amines can be cleaved. Hydrogenolysis of allylic amines of different stereochemistry with NaBH CN was applied to the preparation of both dia-stereoisomers 655 and 657 of cyclopentenylglycine from the cyclic amines 654 and 656 of different stereochemistry[405]. 

The chemistry and stereochemistry of aminoboranes containing the siLicon—nitrogen—boron linkage have been the subject of numerous studies. Many of these compounds are useful precursors to other B—N systems including diboryl-amines (45) and B—H substituted aminoboranes (46). A series of... 

Although the emphasis in this chapter has been on tbe synthesis and mechanism of formation of simple enamines, brief mention will be made of the addition of amines to activated acetylenes to indicate the interest and activity in this area of substituted enamines. Since such additions tend to be stereospecific, inclusion in this section seems apropos. The addition of amines to acetylenes has been much studied 130), but the assigning of the stereochemistry about the newly formed double bond could not be done unequivocally until the techniques of NMR spectroscopy were well developed. In the research efforts described below, NMR spectroscopy was used to determine isomer content and to follow the progress of some of the reactions. 

It is not known whether the amine assists the elimination of the nitrogen, but that the iminium salt retains its stereochemistry has been demonstrated (709). When a mixture of 68 and 69of 1 5 ratio is treated with diazomethane, the ratio of 70 71 obtained in 75% yield and determined spectroscopically was still 1 5. The traw-N-isopropyl-N-methylisobutylidinium perchlorate (69) was prepared by alkylation of an aldimine salt with diazomethanc and... 

The most general method for synthesis of cyclic enamines is the oxidation of tertiary amines with mercuric acetate, which has been investigated primarily by Leonard 111-116) and applied in numerous examples of structural investigation and in syntheses of alkaloids 102,117-121). The requirement of a tram-coplanar arrangement of an a proton and mercury complexed on nitrogen, in the optimum transition state, confers valuable selectivity to the reaction. It may thus be used as a kinetic probe for stereochemistry as well as for the formation of specific enamine isomers. 

Compounds analogous to the cobaltammines may be similarly obtained using chelating amines such as ethythenediamine or bipyridyl, and these too have played an important role in stereochemical studies. Thus ct5-[Co(cn)2(NH3)Cl] was resolved into d(+) and /(—) optical i.so-mers by Werner in 1911 thereby demonstrating. to all but the most determined doubters, its octahedral stereochemistry. More recently, the absolute configuration of one of the optical isomers of [Co(en)3] was determined (.sec Panel on p, 1125),... 

The smooth intramolecular nucleophilic displacement of biphenyl carboxylic acids leading to benzocoumarins (See Section II.A.) inspired also investigation of the behavior of similar diphenyl ether, diphenyl sulfide and A-methyldiphenyl amine derivatives 458 under similar conditions. However, all these attempts to achieve cyclization to tricyclic compounds 459 were unsuccessful, probably due to the unfavorable stereochemistry for the formation of the required seven-mem-bered transition states and also to the presence of the deactivating bridge groups X (Eq. 42) [68JCS(C)1030]. 

To control the stereochemistry of 1,3-dipolar cycloaddidon reacdons, chiral auxiliaries are introduced into either the dipole-part or dipolarophile A recent monograph covers this topic extensively ° therefore, only typical examples are presented here. Alkenes employed in asymmetric 1,3-cycloaddidon can be divided into three main groups (1) chiral allyhc alcohols, f2 chiral amines, and Hi chiral vinyl sulfoxides or vinylphosphine oxides. 

Complete reduction to the alkane occurs when palladium on carbon (Pd/C) is used as catalyst, but hydrogenation can be stopped at the alkene if the less active Lindlar catalyst is used. The Lindlar catalyst is a finely divided palladium metal that has been precipitated onto a calcium carbonate support and then deactivated by treatment with lead acetate and quinoline, an aromatic amine. The hydrogenation occurs with syn stereochemistry (Section 7.5), giving a cis alkene product. 

Name the following amine, including R,S stereochemistry, and draw the product of its reaction with excess iodomethane followed by heating with Ag20 (Hofmann elimination). Is the stereochemistry of the alkene product Z or E Explain. 

In the case of the amide 11 (R = CI13) derived from 2-oxopropanoic amid and amine G the chelation-controlled product is predominantly formed with all organometallic reagents. No reversal of the stereochemistry is observed, presumably for the same steric reason as with the corresponding pyruvic amides derived from amines E and F. 

Another class of configurationally stable a-mctallo amines is derived from the N-tert-butoxy-carbonyl-protected piperidines 32 and 3516, l7. Addition of the lithiated piperidines to aldehydes leads to mixtures of the anti- and. yin-diastereoiners. Although the diastereoselectivity is low, the diastereomers can be readily separated by chromatography since the. vyn-isomer is often in a cyclized form 34. The stereochemistry of the products obtained from piperidines 32 are consistent with an equatorial a-lithiation followed by addition to the aldehyde with retention of configuration. However, with piperidine 35 selective axial lithiation is observed. 

Palladium, (diammine)bis(thiocyanato)-isomerism, 1, 185 Palladium, dichlorobis(amine)-substitution reactions stereochemistry, 1, 318 Palladium, dichlorobis(pyridine)-substitution reactions, 1, 314 Palladium, dinitritobis(triisopropylphosphine)-substitution reactions, I, 314 Palladium, ethylene-synthesis... 

The stereochemistry of the addition of amines to acetylenic sulfones has been investigated by Truce and coworkers74. Reaction of phenyl 1-propynyl sulfone with ethylamine gives a mixture of ( )- and (Z)-isomeric adducts (equation 90)75. 

In recent years, a great variety of primary chiral amines have been obtained in enantiomerically pure form through this methodology. A representative example is the KR of some 2-phenylcycloalkanamines that has been performed by means of aminolysis reactions catalyzed by lipases (Scheme 7.17) [34]. Kazlauskas rule has been followed in all cases. The size of the cycle and the stereochemistry of the chiral centers of the amines had a strong influence on both the enantiomeric ratio and the reaction rate of these aminolysis processes. CALB showed excellent enantioselec-tivities toward frans-2-phenylcyclohexanamine in a variety of reaction conditions ( >150), but the reaction was markedly slower and occurred with very poor enantioselectivity with the cis-isomer, whereas Candida antarctica lipase A (GALA) was the best catalyst for the acylation of cis-2-phenylcyclohexanamine ( = 34) and frans-2-phenylcyclopropanamine ( =7). Resolution of both cis- and frans-2-phenyl-cyclopentanamine was efficiently catalyzed by CALB obtaining all stereoisomers with high enantiomeric excess. 

The SnI reactions do not proceed at bridgehead carbons in [2.2.1] bicyclic systems (p. 397) because planar carbocations cannot form at these carbons. However, carbanions not stabilized by resonance are probably not planar SeI reactions should readily occur with this type of substrate. This is the case. Indeed, the question of carbanion stracture is intimately tied into the problem of the stereochemistry of the SeI reaction. If a carbanion is planar, racemization should occur. If it is pyramidal and can hold its structure, the result should be retention of configuration. On the other hand, even a pyramidal carbanion will give racemization if it cannot hold its structure, that is, if there is pyramidal inversion as with amines (p. 129). Unfortunately, the only carbanions that can be studied easily are those stabilized by resonance, which makes them planar, as expected (p. 233). For simple alkyl carbanions, the main approach to determining structure has been to study the stereochemistry of SeI reactions rather than the other way around. What is found is almost always racemization. Whether this is caused by planar carbanions or by oscillating pyramidal carbanions is not known. In either case, racemization occurs whenever a carbanion is completely free or is symmetrically solvated. 

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