Spiro compounds, stereochemistry

Schroder, H. Netscher, T. Determination of the absolute stereochemistry of vitamin E derived oxa-spiro compounds by NMR spectroscopy. Magrt. Resort. Chem. 2001, 39, 701-708. 

Regardless of the stereochemistry at C-14, both diasteroisomeric indenobenzazepines 176 and 177 afforded the same spiro compound 320. The stereochemistry at C-8 (or C-13) is retained, and the hydroxyl group newly... 

In principle, the approach outlined above for the a-oxoamides can be applied to any reaction, ground or excited state, which converts an achiral reactant into a chiral product, and Toda, Tanaka, and coworkers have investigated a wide variety of such processes [ 15,16]. A complete discussion of their work is beyond the scope of this review, and we illustrate the general approach taken with one final example. As shown in Scheme 4, irradiation of crystalline complexes of ene-diones 20a-f with chiral host (R,R)-(-)-9b led to cyclized products 21a-f in the variable yields and ee values indicated in Table 1 [22]. Remarkably, for reasons that were not clear (there was no accompanying X-ray crystallography), the R=n-propyl derivative 20g was found to give a completely different photoproduct, spiro compound 22 (69% yield, 97% ee, stereochemistry unknown), a result that once again illustrates the rather capricious nature of the use of chiral hosts for asymmetric induction. 

The third example of chirality without a chiral centre is provided by spiro compounds, which we shall meet later when we consider the stereochemistry of polycyclic systems (see Section 3.5.1), but at this stage it is worth noting that they provide a third example of chirality... 

These two examples rely on the rigidity of n systems but this simple saturated system is also chiral. These two rings have to be orthogonal because of the tetrahedral nature of the central carbon atom. There is no chiral centre, but there is no plane of symmetry. Cyclic compounds like this with rings joined at a single C atom are called spiro compounds. Spiro compounds are often chiral even when at a first glance they look quite symmetrical, and you should look particularly carefully for planes of symmetry when you think about their stereochemistry. 

Fig. 48 Chiral spiro compounds with assigned stereochemistry. Left (R)-(-)-[6,6j-vespiren (129), right (R)-(-h)-spiro-bis(anthracene) (130)...

P nuclear magnetic resonance (NMR) spectroscopy has been of great use in determining the coordination state and stereochemistry of the phosphorus atom at the spiro position in spirophosphonia compounds, spirophosphoranes and spiroperphosporanides. The 31P chemical shift is also sensitive to the nature of the atoms directly bonded to the spiro phosphorus center and the size of rings of the spirocyclic system. 

Bycroft et al. [83] have prepared a series of novel 6-spiro-epoxypenicillins 43,44 (Scheme 12) by the reaction of diazopenicillanate 41 with oxalyl chloride followed by reactions with various nucleophiles. These compounds notably exhibit (i-lactam inhibitory and antibacterial properties [84] depending on substituents and stereochemistry of epoxides. These inhibitors possess side-chains, which are highly con-formationally restricted but structurally similar to those of some active penicillins. 

The cis stereochemistry of spiro-(3-lactams 221 was established by NOE experiments and X-ray diffraction analysis. These spiro-(3-lactams would serve as important heterocyclic compounds possessing diverse scaffolds to which different functional groups could be fixed in a stereodefined 3D topological arrangement. 

Grosu et al. also synthesized a variety of new 5,5-disubstituted (96MI71) and 2,2,5,5-tetrasubstituted 1,3-dioxanes (98M723) the compounds exhibit anancomeric structures with the bulkier substituents in an equatorial conformation. The same authors also studied the stereochemistry of trispiro- (98M59), dispiro- (96T12783), and spiro- 1,3-dioxanes (97T6215), when the substituents are close to the spiro carbon atoms, they induce anancomericity of the heterocycle, and when they are further away, the 1,3-dioxanes proved to be flexible. 

The structure and absolute stereochemistry of hinesol (282) has now been firmly established by an unequivocal synthesis which involved the tricyclic dienone (329) prepared from 6-methoxy-l-tetralone. Treatment of the dienone with lithium dimethylcopper gave a mixture of syn and anti enones (330). By a series of stereoselective reactions this compound was converted to the diol (331) whose mono-mesylate underwent a base-induced cleavage to give the spiro[4,5]-ketone (332). Elaboration of this ketone to hinesol was accomplished along... 

The five coordinate spirophosphoranes have played an important role with respect to understanding the stereochemistry of four coordinate phosphorus reactions which proceed via phos-phorane intermediates. Variable temperature NMR studies have established the apicophilicities of a wide range of groups (i.e. relative preferences of a series of groups to occupy an apical position rather than an equatorial position of a trigonal bipyramidal (t.b.p.) conformation of a phosphorane). The spiro ring system has been used to stabilize transient reaction intermediates of acyclic compounds, for example hydrolysis intermediates such as hydroxyphosphoranes. 

Many five coordinate phosphorane compounds have been examined, the keen interest arising primarily from the variation of structures which have relevance with respect to their stereochemical importance as reactive intermediates in the reaction pathways of four coordinate compounds <74JA4143>. The stereochemistry of phosphoranes vary on a structural coordinate between trigonal bipyramidal (t.b.p.) and square pyramidal (s.p.). Phosphoranes which have been found to have conformations closer to the t.b.p stereochemistry include thienyl phosphorane (33 R = H, = 2-thienyl) <83ZN(B)466>, spiro(4,4)phosphoranes (41) <77JA3332>, (47) <89PS(45)255>, (42 R = Ph,... 

The structures of these two compounds were obtained by extensive application of 2D NMR techniques and mass spectrometry [98]. These tetra- and penta-cyclic compounds possess long dialkyl chains and free carboxyl groups. The authors elegantly applied isotope-induced C shifts in the establishment of the nature and location of the two hydroxyl groups and the free carboxyl group in CP-225917. Two of the hydroxyl groups of CP-225917 are cyclized to form a spiro-acetal ring in compound CP-263114. The stereochemistry of these compounds was elucidated by... 

Nortryptoquivaline (FTD, 77), C2gH2gN407, mp 256-258°C, [a] -1-170°, produces a UV spectrum similar to that of tryptoquivaline (FTC), and all IR absorptions associated with functional groups are identical in these two compounds. The NMR spectrum of 77 is identical to that of FTC except that a doublet methyl (81.58, 7 = 7 Hz) appears instead of two singlet methyls (81.47 and 1.49) in FTC. Therefore 77 is nor derivative, and its CD spectrum indicates the stereochemistry relative to FTC. Yamazaki s FTD was identified as nortryptoquivaline by direct comparison (756). A single-crystal X-ray diffraction experiment was performed on nortryptoquivaline, and the absolute configuration was established as 2-S,3-S, 12-7 , 15-5,27-S. The existence of the spiro-y-lactone was also confirmed (757). 

Pentanortriterpenoids.—The intriguing range of compounds isolated from the family Cneoraceae continues to be extended. The availability of tricoccin 842 the C-7 epimer of tricoccin 84 (see Vol. 10, p. 151), has led to a revision of the stereochemistry of the latter. Tricoccins 84 and 842 are now represented by structures (53) and (54) respectively. Tricoccins 816 and 82 are the bishemiacetal (55) and the corresponding peroxide (56). Both are extremely acid sensitive, readily losing water to form the spiro-acetals (57) and (58) respectively. The structures of cneorins Q (59) and NP29 (60) have been established. They differ only in the stereochemistry at C-7 and C-9. ... 

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