Tris diastereomers

Addition of tetra(isopropoxy)titanium results in a slight increase in yield, but does not lead to an exchange of the cation which can be accomplished with tri(isopropoxy)titanium chloride (Section D.1.3.3.3.8.2.3.). In none of these cases could a trace of a second diastereomer be detected112,113. 

Tributyl[( )-l-(methoxymethoxy)-2-butenyl]stannane (4) is available by the addition of tri-butyltin lithium to 2-butenal followed by treatment with chloromethoxymenthane 03. The resulting diastereomers were separated by chromatography to give stereochemically homogeneous a-alkoxystannanes 5 and 6104. 

A closely related method does not require conversion of enantiomers to diastereomers but relies on the fact that (in principle, at least) enantiomers have different NMR spectra in a chiral solvent, or when mixed with a chiral molecule (in which case transient diastereomeric species may form). In such cases, the peaks may be separated enough to permit the proportions of enantiomers to be determined from their intensities. Another variation, which gives better results in many cases, is to use an achiral solvent but with the addition of a chiral lanthanide shift reagent such as tris[3-trifiuoroacetyl-Lanthanide shift reagents have the property of spreading NMR peaks of compounds with which they can form coordination compounds, for examples, alcohols, carbonyl compounds, amines, and so on. Chiral lanthanide shift reagents shift the peaks of the two enantiomers of many such compounds to different extents. 

The first two principles were successfully applied by Scott et al. for the preparation of tri- and tetra-ferf-butylphospha[3]- and -[4]pericyclines 67 and 68, respectively (Scheme 13) [19]. While 67 was obtained as a single compound, the frans-diastereomer, the tetraphospha[4]pericycline 68 was obtained as a mixture of four diastereomers. 

A similar reaction sequence, which begins with the trisphosphitylation of mannitol (12) afforded three P-diastereomers of cyclic trithiophosphate 13 via the corresponding tricoordinated tris-chlorophosphite and amidophosphite (Scheme 5) [20],... 

Scheme 5 Synthesis of P-diastereomers of cyclic tris-thiophosphate 13...

The scheme below depicts the novel use of a carbonyl ene cyclization (A, Lewis acid-catalyzed) and a closely related Prins cyclization (B, Brpnsted acid-catalyzed) to generate predominantly trans (cyclization condition A) or cis (cyclization condition B), di and tri substituted piperidines 160 and 161 <06JOC2460 06OBC51>. Of note, in the formation of di-substituted derivatives, R1 = H and R2 = Ph, no reaction occurs under cyclization condition B and the cis isomer 160 is obtained exclusively under cyclization condition A. In the case of tri-substituted derivatives, when bulky substituents at the 2-position (R1 = f-Bu or Ph) are present the trans diastereomer 161 is obtained almost exclusively under cyclization condition A, while no diastereoselectivity is seen under cyclization condition B. 

In order to gain more insight into this proposed mechanism, Montgomery and co-workers tried to isolate the intermediate metallacycle. This effort has also led to the development of a new [2 + 2 + 2]-reaction.226 It has been found that the presence of bipyridine (bpy) or tetramethylethylenediamine (TMEDA) makes the isolation of the desired metallacycles possible, and these metallacycles are characterized by X-ray analysis (Scheme 56).227 Besides important mechanistic implications for enyne isomerizations or intramolecular [4 + 2]-cycloadditions,228 the TMEDA-stabilized seven-membered nickel enolates 224 have been further trapped in aldol reactions, opening an access to complex polycyclic compounds and notably triquinanes. Thus, up to three rings can be generated in the intramolecular version of the reaction, for example, spirocycle 223 was obtained in 49% yield as a single diastereomer from dialdehyde 222 (Scheme 56).229... 

One can try to figure out from the pictures how two diastereomeric intermediates are formed. It is more convenient to adopt a formal approach. We can explain the formation of enantiomers when a metal (even a bare Ag+ ion would do) co-ordinates to our alkene substrate, and equally so the formation of diastereomers in Figure 4.5. 

Zraro-pyridine donors) have been determined,and the fac and mer isomers of [Ru(219)3] + and two diastereomers of [Ru(219)2(bpy)] " " have been isolated using HPLC, and EPR spectroscopic data for the singly reduced species have been analyzed. A general strategy for the synthesis of [Ru(218)3]"+ has been included in a study of routes to tris(bpy), tris(phen), and tris(218) complexes of Ru and A comparison has been made between the photoinduced oxidative... 

As you read the rest of the table and text in excerpt 4G, you will see that the authors tried a number of different reaction conditions to maximize the yield of (R,S)-3, the diastereomer that is ultimately converted to the (S) a-amino acid. 

This methodology was applied to a two-step sequence for the preparation of enantio-merically enriched dihydrobenzo[h]furans (Scheme 10.11) [46]. Rhodium-catalyzed allylic etherification of (S)-47 (>99% ee), with the sodium anion of 2-iodo-6-methyl-phenol, furnished the corresponding aryl allyl ethers (S)-48/49 as a 28 1 mixture of regioisomers favoring (S)-48 (92% cee). Treatment of the aryl iodide (S)-48 with tris(trimethylsilyl)silane and triethylborane furnished the dihydrobenzo[h]furan derivatives 50a/50b as a 29 1 mixture of diastereomers [43]. 

The ratio of diastereomers of the crude or purified SAMP-hydrazones can be measured by H-NMR shift experiments5. For example, using tris(6,6,7,7,8,8,8-heptafluoro-2,2-dimethyl-3,5-octanedionato)europium [Eu(fod)3] or tris[3-(heptafluorobutanoyl)-(1 / )-camphorato]europium [Eu(hfc)3] as shift reagent, the sharp methoxy singlet at 3.2 3.4 ppm is shifted to lower field by about 1 to 4 ppm, which allows the determination of each diastereomer present. 

In a synthetic application of this double inversion sequence, tris(benzyloxy)bromo boronic ester 6 obtained in the ribose sequence (Section 1.1.2.1.3.2.) is converted to the 4-methoxyphenyl-methoxy derivative 7 in the usual way. 2,3-Dichloro-5,6-dicyano-l,4-benzoquinone cleaves the protecting group to furnish the a-hydroxy boronic ester 8. Conversion of the a-hydroxy boronic ester 8 to the methanesulfonate 9 followed by displacement of the sulfonate by phenylmethoxide yields a-benzyloxy boronic ester 10, which is a diastereomer of one of the ribose intermediates37. 

Somei-Kamatani coupling of 116 [Fig. (32)] with the gramine derivative 94 in the presence of tri(n-butyl)phosphine gave the tryptophan derivative 117 as a 3 1 mixture of diastereomers in 70% yield. 

The reaction of 3,3,3-trifluoropropene with a sulfur tetrafluoride/hydrogen fluoride/disul-fur dichloride system proceeds at 20 C to give a mixture of diastereomers of bis[2-fluoro-l-(tri-fluoromethyl)ethyl] sulfide (18) in high yield.243... 

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