Symmetrical adducts

Seven of these were found after cyclopropanation of e- and trans-n-Cg2(COOEt)4 (n = 2-4) (4-7) with diethylmalonate (Figure 10.6) [20]. In a few cases, such as the Cj-symmetric adduct 8 (e,e,e-addition pattern), the structure can be assigned based on NMR spectroscopy alone. NMR spectroscopy allows for the determination of the point group of the adduct. The e,e,e-addition pattern is the only one that has Cj-symmetry and as a consequence the assignment is unambiguous. The same is true for the Dj-symmetrical adduct 9. Conversely, C2-, C - or Cj-symmetry of trisadducts can arise from different addition patterns. The structural assignment of such adducts requires the additional analysis of their possible formation pathways. 

Compounds with Metal-Metal Bonds. There is one clear example of the addition of a compound with a metal-metal bond to an olefin. Cobalt octacarbonyl reacts with tetrafluoroethylene to form a symmetrical adduct (102). 

In this brief overview of C70-addition patterns, it may also be mentioned that photochemical addition of l,l,2,2-tetramesityl-l,2-disilirane afforded a C2-symmetric adduct for which the unusual addition across the equatorial,... 

The propensity for Claisen-Schmidt condensation to afford bis-adducts [e.g., ( , )-2,6-dibenzylidenecyclohexanone from benzaldehyde and cyclohexanone] virtually exclusively, even in the presence of excess ketone (as mentioned in Section 6.2.3), was the cornerstone of our strategy for the preparation of symmetrical adducts (i.e., those with a two-fold axis through the C=O group as viewed in the plane of the page)." Such condensations occur sequentially, as mono-condensed products tend to be more reactive than the parent cycloalkanones under the reaction conditions, making them transient intermediates prepared for further reaction. 

In 2011, Nissen and Detert [9] reported a partially intramolecular [2+2+2] aromatization for the synthesis of lavendamycin (Scheme 9.4). Lavendamydn is an antitumor antibiotic produced by Straptomyces lavendulae. Both Rh and Ru catalyses were used for this [2+2+2] cycloaddition of a 1,6-diyne and an electron-deficient nitrile. What was interesting was the observation that the symmetrical adduct was always preferred with Rh catalysis, and when Ru catalysis was employed, only the desired unsymmetrical p-carboline product was obtained. The pentacyclic core of lavendamycin was then converted to lavendamydn methyl ester via a sequence of functional group manipulations. 

A C-H activation process was also utilized in the preparation of symmetrical and unsymmetrical 4,7-diaryl-2,l,3-benzothiadiazoles. The diarylation was performed on 2,1,3-benzothiazoles, affording the corresponding symmetrical adducts (eq 26).31... 

Synthesis We need the symmetrical double adduct from acetone and acetylene. 

The yellow compound BsF 2 appears to have a diborane-like structure (112) and this readily undergoes symmetrical cleavage with a variety of ligands such as CO, PF3, PCI3, PH3, ASH3 and SMe2 to give adducts L.B(BF2)3 which are stable at room temperature in the absence of air or moisture. 

In the present instance, protonation of the C1-C2 double bond gives a carbo-cation that can react further to give the 1,2 adduct 3-chloro-3-methylcyclohexene and the 1,4 adduct 3-chloro-L-methylcyclohexene. Protonation of the C3-C4 double bond gives a symmetrical carbocation, whose two resonance forms are equivalent. Thus, the 1,2 adduct and the 1,4 adduct have the same structure 6-chloro-l-methyl-cyclohexene. Of the two possible modes of protonation, the first is more likely because it yields a tertiary allylic cation rather than a secondary allylic cation. 

H-Azepines 1 undergo a temperature-dependent dimerization process. At low temperatures a kinetically controlled, thermally allowed [6 + 4] 7t-cycloaddition takes place to give the un-symmetrical e.w-adducts, e.g. 2.231-248-249 At higher temperatures (100-200°C) the symmetrical, thermodynamically favored [6 + 6] rc-adducts, e.g. 3, are produced. These [6 + 6] adducts probably arise by a radical process, since a concerted [6 + 6] tt-cycloaddition is forbidden on orbital symmetry grounds, as is a thermal [l,3]-sigmatropic C2 —CIO shift of the unsym-metrical [6 + 4] 7t-dimer. 

In contrast, the 6,8-dichloro 7 and 6,8-dimethyl derivatives, in which [6 + 4] dimerization would locate a substituent at the bridgehead position, form the symmetrical [6+6] adducts, e.g. 8.154... 

Chlorins, e.g. 14, form adducts with osmium(VIII) oxide, which can be hydrolyzed in aqueous sodium sulfide to bacteriochlorindiols, e g. 2, or isobacteriochlorindiols, e.g. 3. Thus, similar to diimide reductions of chlorins, metal-free tetraphenylchlorin 14 (M = 2H) is selectively oxidized to a corresponding bacteriochlorin 2 whereas the zinc chlorin gives an isobac-teriochlorin 3 on oxidation with osmium(VIII) oxide.40 With less symmetrical chlorins, very complex mixtures of constitutional isomers and stereoisomers are formed by /i-bishydroxyla-tion.17... 

The following C2-symmetric bis-sulfonamide is a more efficient controller of stereoselectivity in aldol additions. The incorporation of this ligand into the bromodiazaborolane, subsequent generation of the boron enolate derived from 3-pentanone, and addition to achiral aldehydes preferentially leads to the formation of ijn-adducts (synjanti 94 6 to >98 2) with 95-98% ee. Chemical yields of 85-95% are achieved51. 

Use of the valine derived (4S )-3-acetyl-4-isopropyl-1,3-oxazolidine (8)92, the C2-symmetric reagents (2.5,55)-l-acetyl-2,5-bissubstituted pyrrolidine 994, or the doubly deprotonated acetyl urea /V-acetyl- V..V -bis[(.S)-l-phcnylethyl]urea (10), also does not lead to sufficient induced stereoselectivity combined with acceptable chemical yield. When the acetyl urea enolate is reacted with aliphatic and aromatic aldehydes, the diastereomeric adducts (ratios ranging from 1 1 to 3 1) may be separated by column chromatography to give ultimately both enantiomers of the 3-hydroxy acids in 99% ee110. 

Aldol reactions of a-substituted iron-acetyl enolates such as 1 generate a stcrcogenic center at the a-carbon, which engenders the possibility of two diastereomeric aldol adducts 2 and 3 on reaction with symmetrical ketones, and the possibility of four diastereomeric aldol adducts 4, 5, 6, and 7 on reaction with aldehydes or unsymmetrical ketones. The following sections describe the asymmetric aldol reactions of chiral enolate species such as 1. 

The lithium enolate 2a (M = Li ) prepared from the iron propanoyl complex 1 reacts with symmetrical ketones to produce the diastercomers 3 and 4 with moderate selectivity for diastereomer 3. The yields of the aldol adducts are poor deprotonation of the substrate ketone is reported to be the dominant reaction pathway45. However, transmetalation of the lithium enolate 2a by treatment with one equivalent of copper cyanide at —40 C generates the copper enolate 2b (M = Cu ) which reacts with symmetrical ketones at — 78 °C to selectively produce diastereomer 3 in good yield. Diastereomeric ratios in excess of 92 8 are reported with efficient stereoselection requiring the addition of exactly one equivalent of copper cyanide at the transmetalation step45. Small amounts of triphcnylphosphane, a common trace impurity remaining from the preparation of these iron-acyl complexes, appear to suppress formation of the copper enolate. Thus, the starting iron complex must be carefully purified. 

In the course of studying the bromination reactions of the bicyclic systems we noticed that the reaction temperature has a dramatic influence on the product distribution. Increasing of the temperature gives non-rearranged reaction products (refs. 1,2). For this reason, we submitted 1 to high temperature bromination. To a solution of 1 in decalin at 150 C was added a hot solution of bromine in decalin in one portion. The colour of bromine disappeared immediately. After silica gel chromatography followed by fractional crystallization we isolated four products 2-6 in yields 8, 35, 37, and 9 % respectively. The structure of these compounds has been elucidated on the basis of spectral data by iH NMR and NMR experiments and by comparison with those reported in the literature. Symmetrical endo-c/5-isomer 6 has been observed for the first time. Studies concerning the mechanism of syn-addition show that the syn-adduct can arise either from direct... 

In most cases, more 1,4- than 1,2-addition product is obtained. This may be a consequence of thermodynamic control of products, as against kinetic. In most cases, under the reaction conditions, 15 is converted to a mixture of 15 and 16, which is richer in 16. That is, either isomer gives the same mixture of both, which contains more 16. It was found that at low temperatures, butadiene and HCl gave only 20-25% 1,4 adduct, while at high temperatures, where attainment of equilibrium is more likely, the mixture contained 75% 1,4 product. 1,2 Addition predominated over 1,4 in the reaction between DCl and 1,3-pentadiene, where the intermediate was the symmetrical (except for the D label) HjCHC—CH—CHCH2D. Ion pairs were invoked to explain this result, since a free ion would be expected to be attacked by Cl equally well at both positions, except for the very small isotope effect. 

Ansuer Enone disconnection (33a) reveals symmetrical diketone (34), an obvious Diels-Alder adduct. 

Disconnection of the acetals leads nowhere but a,P disconnection (21a) gives symmetrical (22). This is a 1,6-dicarbonyl compound and can be reconnected to (23). Removal of the acetals now reveals a Diels-Alder adduct (24). 

The diketo-ester (1) has 1,4 1,5 and 1,6-dicarbonyl relationships. Both the 1,4 and 1,5 relationships can be disconnected at the branchpoint in the middle of the molecule, to give sensible intermediates such as (3) and (4), but difficult synthons (2) and (5). The 1,6 reconnection requires symmetrical Diels-Alder adduct (6). 

Unfortunately the double bond in (24) is not conjugated with the carbonyl group so that the 2+2 cyclo-addition does not give a good yield. It is also un-symmetrical so that a mixture of adducts is formed. Attempts to solve the first of these problems by using (25) or (26) made the second problem worse as the wrong adduct, e.g. (27) is the major isomer. 

In 2007, a novel C2-symmetric diphenylthiophosphoramide ligand was found to be a fairly efficient chiral ligand for the Cu(I)-promoted 1,3-dipolar cycloaddition of imines and pyrrole-2,5-dione derivatives to give the corresponding adducts in moderate to good enantioselectivities and good yields (Scheme 10.14). ... 

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