Norbomanone

An unexpected reduction of enamines by secondary amines such as pyrrolidine, piperidine, and particularly hexamethyleneimine was discovered in the formation of the norbomanone enamines and extended to hexamethyleneiminocyclopentene (561,562). 

Facial selectivities in the nucleophilic addition of bicyclic ketones have recently been examined comprehensively [71, 72]. Mehta and his colleagues studied the facial selectivities of 2,3-exo,exo-disubstituted 7-norbomanones 14a and 14b [73-75]. In the reduction of 14a and 14b with sodium borohydride, lithium aluminum hydride. 

Mehta et al. also studied the facial selectivities of 5,6-exo,eji o-disubstituted bicyclo[2.2.2]octan-2-ones 18 [75, 78]. These systems are related to the 2,3-exo,ex( -disubstituted 7-norbomanones 14, but differ in the direction of the carbonyl n face. Hydride reduction of 5,6-exo,ex( -disubstituted bicyclo[2.2.2] octan-2-ones (18) with NaBH and DIBAL-H and methylation with MeLi were smdied [75, 78],... 

The exo reactivity of 2-norbomanone 25 in nucleophilic addition (such as reduction with hydride) is a classical example of the facial selectivity of carbonyl groups in bicyclic systems [80]. 

Norbomenone 26 undergoes reduction by sodium borohydride under kinetic conditions to produce 5% exo- (i.e., endo attack) and 95% endo- (i.e., exo attack) 2-norbomeol. This leads to the partial rate constants of 11.4 for exo and 0.6 for endo attack (relative rate with respect to the rate of LiAlH reduction of cyclopen-tanone (1.00)) [80]. In the saturated 2-norbomanone 25, the values are 4.55 for exo and 0.74 for endo attack. Thus, the introduction of the double bond enhances the... 

Cycloaddition of bicyclo[2.2.1]hept-2-ene-2,3-dicarboxylic anhydride 81 with cyclopentadiene was also studied by Bartlett et al., who found exclusive top addition, the top-endo/top-exo ratio being 3 2 [147]. The endolexo ratio is significantly different from that of 80 (60-70 1). The observed top selectivity in norbornadiene (80) and norbomene (81) derivatives is consistent with the inherent top reactivity of norbomanone 25 and norbomene 57. Orbital unsymmetrization of the dienophile... 

Cells of Acinetobacter sp. NCIB 9871 grown with cyclohexanol carried out enantiomeri-cally specific degradation of a racemic substituted norbomanone to a single ketone having >95% enantiomeric excess (Levitt et al. 1990). 

D-2-OXO-7,7-DIM ETHYL-1-VINYLBICYCLO[2.2.1]HEPTANE (2-Norbomanone, 7,7-dimethyl-l-vinyl-, D-)... 

Camphor oxime (1,7,7-trimethyl-2-norbomanone oxime) C10H17NO —164.0 2... 

More recently, it was demonstrated that 80 is a catalyst for the partial oxidation of olefins using dioxygen (230). For example, dry propene was oxidized to acetone when water vapor was present in the catalyst stream, some propanal could also be detected. Other reactions reported included the conversion of styrene to acetophenone and phenylacetaldehyde in an 80 20 product ratio, and 2-norbornene to 2-norbomanone and cyclohexene-4-carboxyaldehyde in a 70 30 product ratio. 

Cyclohexanone oxygenase from Acinetobacteria converts a variety of alicyclic ketones into lactones in a regio- and enantioselective manner (Table 12). The reaction can be carried out by a whole-cell process (181) or with the isolated enzyme (178). For example, 2-norbomanone [497-38-1] (112) is converted to the corresponding lactone in 81% yield (178). The enzyme, however, is not selective both enantiomers react equally well. The oxidation rate of camphor [76-22-2] (113), is about one-third that of (112) nevertheless, given sufficient amount of time, the product yield reaches 89%. Substituted cylohexanones (114) and cyclopentanones (115) are converted into the corresponding lactones in moderate to good yield and selectivity (179—181). 

We thus start with the smallest and simplest systems for which we have thermochemical data, the isomeric 2- and 7-bicyclo[2.2.1]heptanones (the norbomanones, 39a and 39b). Our intuition suggests that the latter species is more strained since the increased geometric constraints of a single-carbon bridge over those for a two-carbon bridge are... 

What can be said about the thermochemistry of methylated cyclic ketones in any phase other than liquid In that we would have discussed gas-phase species if the data were available, what we are really asking is what can be said about the species of interest as solids , Let us generalize this to see what can be said about the thermochemistry of cyclic ketones as solids. In that the cyclic ketones in the previous section were all formally quite strain-free derivatives of cyclopentanone or cyclohexanone, let us now consider only such species and their cycloalkane analogs. There are no enthalpy-of-fusion data available for cyclopentanone. For cyclohexanone, the temperature-uncorrected fusion enthalpy is about 1.3 kJmol-1—we arbitrarily ignore in this discussion enthalpies of any crystal - different crystal phase enthalpy. The same treatment for cyclohexane discloses the fusion enthalpy of 2.7 kJmol-1. Accordingly, the earlier reported value of 638(6) = 104.4 for the gas phase is sequentially modified to ca 115 kJ mol-1 for the liquid and to 113 kJmol-1 for the solid. For 2-norbomanone, adamantanone and diamantanone (39a, 42 and 43), the gas-phase differences of 115.7 6.8, 96.0 5.1 and 90.6 3.2 become for the solids 124.4 6.8, 116.9 4.5 and 97.8 3.1 kJmol-1. Very roughly, 639( ) is some 10 kJmol-1 more positive for solids than for gases and 639(8) is about 113 kJmol-1 for all of the solids discussed here. 

TABLE 2. Observed and calculated syn. anti ratios for nucleophilic attack on 7-norbomanones... 

Unhindered ketones can be deoxygenated by hydrogenation with this catalyst.4 Stcric hindrance can prevent this reaction. Thus, 2-norbomanone does not react, although camphor is reduced. The alcohols corresponding to inactive ketones are reduced. Cyclopentanone is reduced to cyclopentane in 24% yield cyclohexanone is reduced in 90%yield. When successful, this method is a useful one-step deoxygenation. 

The stereodescriptors endo and exo are used to distinguish between the positions of a substituent beneath or outside the concave area of a bent molecule. For example, in the major product of the reduction of norbomanone with Li BH (sec-Bu)3 (Formula A in Figure 10.10) the added H atom is oriented exo and the OH group obtained endo. 

Other cyclic or bicyclic ketones do not have a convex side but only a less concave and a more concave side. Thus, a hydride donor can add to such a carbonyl group only from a concave side. Because of the steric hindrance, this normally results in a decrease in the reactivity. However, the addition of this hydride donor is still less disfavored when it takes place from the less concave (i.e., the less hindered) side. As shown in Figure 10.10 (top) by means of the comparison of two reductions of norbomanone, this effect is more noticeable for a bulky hydride donor such as L-Selectride than for a small hydride donor such as NaBH4. As can be seen from Figure 10.10 (bottom), the additions of all hydride donors to the norbomanone derivative B (camphor) take place with the opposite diastereoselectivity. As indicated for each substrate, the common selectivity-determining factor remains the principle that the reaction with hydride takes place preferentially from the less hindered side of the molecule. 

Figure 4. (Left) Structures of norbomanones. (Right) CD curves (plots of Ae vs X) for the enantiomeric 2-norboman-ones. For the carbonyl n - t transition, the +Ae curve is associated with the (11 ) enantiomer and the -Ae curve with the (IS) isomer. An equal mixture of the enantiomers (racemic mixture), or the achiral isomer. 7-norboma-none, would have Ae=0 over the range of X.

Table VII. Structures, octant diagrams and observed n - x CD Cotton effects for 0-deuterioadamantanones and 2-deuterio-7-norbomanones.

Due to recurring problems with the treatment of methyl rotations in calculations of vibrational averages of optical rotations, Mort and Autschbach [149] have proposed a computational protocol for a separate treatment of hindered rotations. In a nutshell, in this approach a quasi-free rotation of a functional group is treated separately from the vibrational average, with numerically calculated hindered-rotor wavefunctions. With regards to optical activity, the authors studied their protocol on three molecules (R)-methyloxirane, (lS)-norbomanone, and... 

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