Nonane-1,3-diol

The related reagent (diisopropoxymethylsilyl)methylmagnesium chloride (9) has been used similarly to hydroxymethylate organic halides and mesylates. 

---

Inactivated alkenes are oxidatively cleaved by the hydrotrioxide to give ketones. For example, methyl oleate 73 reacts with the hydrotrioxide to produce two aldehydes, followed by LiAlFLj reduction to give 1-nonanol and nonane-1,9- diol in 64 and 74% yields (equation 81). 

The trifluoroacetates of 1-hexanol and 1-heptanol had retention times of 3.0 and 5.1 minutes, respectively, on Carbowax at 80°C. The trifluoroacetates of 1-undecanol, nonane-1,9-diol, and decane-1,10-diol had retention times of 4.0, 5.1, and 7.6 minutes on Apiezon at 170°C. Peaks were well formed and did not have the characteristic tail of alcohol peaks. The reduction-trifluoroacetylation treatment of 5-ketohexanoic... 

In the Kuraray process for the production of nonane-1,9-diol two steps involve the use of aqueous biphasic catalysis Pd/tppms catalyzed telomerization of butadiene with water as a reactant and Rh/tppms catalyzed hydroformylation (Fig. 7.14) [51]. 

Heomatka and Aub [34] have established for diols a linear relation between the log of the /-value and the number of carbon atoms when using absolute ethanol or dioxan on silica gel G layers they studied ethylene glycol, propane-1,3-diol, hexane-1,6-diol, heptane-1,7-diol, nonane-1,9-diol, decane-1,10-diol and tridecane-1,13-diol. 

For structures with more complex hydrogen-bond patterns, a hierarchy of graph set symbols is generated, and it is beyond the scope of this chapter to go into details. As an example, we take the bicyclo[3.3.1]nonane diols 7 and 8... 

The 1,4-isomer has been similarly generated from terephthalonitdle [623-26-7] (56) using a mixed Pd/Ru catalyst and ammonia plus solvent at 125 °C and 10 MPa (100 atm). It is also potentially derived (57) from terephthaUc acid [100-21-0] by amination of 1,4-cyclohexanedimethanol (30) [105-08-8], Endocyclization, however, competes favorably and results in formation of the secondary amine (31) 3-a2abicyclo[3.2.2]nonane [283-24-9] upon diol reaction with ammonia over dehydration and dehydrogenation catalysts (58) ... 

In 1979 the bieyclic diol exo-2,ejco-6-dihydroxy-2,6-dimethylbicyclo[3.3.1]nonane (i) was prepared and observed to co-crystallise with various solvents, including ethyl acetate, chloroform, toluene, dioxane, and acetone. A crystal structure determination of the ethyl acetate compound revealed the occurrence of a helical canal host structure, containing ethyl acetate as guest (with 3 1 diol ethyl acetate stoichiometry), and that spontaneous resolution had occurred on crystallisation of the multimolecular inclusion compound 6>. 

The role of the methyl substituents in the diol host molecule was assessed by preparation of the homologues of 1 with hydrogen [ejco-2,ejco-6-dihydroxybicyclo-[3.3.1]nonane, (5)] and ethyl [exo-2,exo-6-dihydroxy-2,6-diethylbicyclo[3.3.1 Jnonane, (6)] substituents11 . Neither compound showed evidence of inclusion, or forma-... 

Fig. 4. Diagrammatic representation of layered crystal structures of rigid diols, with closed hydrogen bonding cycles. Open circles are oxygen atoms, filled circles hydrogen atoms, and the solid lines represent the connecting diol. Hydrogen bonds are shown as broken lines, (a) The structure of 2,6-dihydroxy-2,6-dimethyltricyclo[3.3.1.13,7]decane (4). (b) The structure of erafo-2,e do-6-dihydroxy-2,6-dimethylbicyclo[3.3.1]nonane, (7)...

A chiral diphosphite based on binaphthol, coordinated with rhodium (I) forming a nine-member ed ring, led to an efficient hydroformylation of vinylarenes, although moderate ees were obtained (up to 46%) at mild pressure and temperature reaction conditions.364 Chiral diphosphites and phosphinite-phosphites derived from spiro[4.4]nonane-l,6-diol were synthesized. Using these catalysts in the asymmetric hydroformylation of styrene, high regioselectivity (97%) and... 

Nieman and Keay198 reported the use of c/.v,c/s-spiro 4,4]nonanc-1, 6-diol as a new chiral auxiliary to be used in asymmetric Diels-Alder reactions. Their best results in a series of reactions between chiral acrylates and cyclopentadiene were obtained when the pivalate ester of ds,ds-spiro[4,4]nonane-l,6-diol was used as the chiral auxiliary. When 318 was treated with cyclopentadiene, the expected endo adduct 319 was obtained with more than 97% de (equation 88). 

The synthesis of a new class of compounds possessing the general structure 4,4,8,8-tetraalkyl-2,3 6,7-dibenzo-9-azabicyclo[3.3.1]nonane-l,5-diol (84) deserves mention since the basic skeleton is analogous to that of the pavines (Scheme 12) (124-129). Oxidation of a series of indeno[2,l-a]indenes 82 with chromic acid yielded dibenzocyclooctanediones 83. Treatment of these diketones with various amines resulted in a transannular reaction to afford species 84 in good yields. 

A chiral complex was used in Ru(N0)Cl(salen )/02/UV/CHCl3 for oxidative desymmetrisation of meso-diols to optically active lactols and lactones, e.g. of cis-1,2 -bis(hydroxyhnethyl)-cyclohexane to (1/ , 6S, 7/ 5)-7-hydroxy-8-oxabicyclo[4.3.0] nonane, cf mech. Ch. 1 [363],... 

Nonane-2-8-diol, 3-4-epoxy-5-iso-propyl-2-metyl, (3-R-4-S-5-S-8-e) Lf 0.006 Nona-trans-2-en-8-ol, 3-methyl-4-oxo Lf T476 Nona-trans-2-trans-6-dienal, 5-iso-propyl-2-methyl-8-oxo Lf 0.004 " Non-ds-6-en-4-olide Lf 0.36 ... 

Bicyclo[5.2.0]nonane-l,7-diol was oxidized by potassium periodate in water at room temperature to yield cyclononane-1,4-dione (6). 56... 

Decarbonylation is observed, however, in substituted 9,10-epoxycholestan-6-ones,104 and Norrish Type II photocyclization, leading to the formation of cyclobutanols, is preferred in other y-epoxy ketones.105 A photoreaction of a different type has been observed in the bicyclo[3.3.1]nonane (126) and affords the diol (127).106... 

Photochemically induced transannular ring closure of bicyclo[3-3.1 -nonane-3,7-dione to 3,7-noradamantane diol is illustrated in Eq. (38)12S). 

We have observed that diol 3, cis-2-butene-l,4-diol, and cis-1,2-bis(hydroxymethyl)cyclohexane react smoothly with TPP-CClq to afford 4 (78%), 2,5-dihydrofuran (65%), and cis-8-oxabicyclo[4.3.0]-nonane 84%). Reaction of diol 5 with TPP-CCli in CH3 CN gives 52% of 5-chloropentanol, 6 (11%), and 1,5-dichloropentane (25%) while diol 7 affords 6-chlorohexanol (48%) and 1,6-dichlorohexane (39%). Comparisons of the ether chlorohydrin dichloride product distributions arising from these simple diols reveal a trend for efficiency of chain closure to 3 - 7 membered rings where the formation of cyclic ethers appear to decrease in order of the following ring size 3-5>6>4-7. 

Successive treatment with either SC12 or S2CI2 and SOCl2 converts 1,5-cyclooctadiene into 2,6-dichloro-9-thiabicyclo-[3.3.1]nonane 466. Both halogen atoms can be replaced by a wide variety of nucleophiles <2001JOC4386>. Following hydrolysis to the 2,6-diol, Swern oxidation affords the 2,6-dione (Scheme 160) < 19980SC692>. 

The absolute configuration of (-)-spiro[4.4]nonane-l,6-dione was determined by application of Horeau s method of optical rotations.[45] In support of the assignment, and with greater certainty, the Exciton Chirality Rule was applied to the bis-p-dimethylamino-benzoate of the cis,trans-diol obtained following reduction of the diketone. The cis,trans-diol is readily distinguished by NMR from the C2-symmetry cis,cis and rrans,rrans-diols. Since the cis,trans-diol dibenzoate from the (-)-dione exhibits a (-) exciton chirality CD, it follows that the absolute configuration of the dione is that shown in Figure 37. The absolute stereochemistry is easily determined by CD. 

Figure 37. (a) Formation of the ds,trans-diol of (-)-spiro[4.4]nonane-l,6-dione. (b) Observed CD of the bis-p-dimethylaminobenzoate of the cis,trans-diol. (c) Exciton chirality. 

An improved route to 2a-hydroxycholesterol has been devised as part of the preparation of 2a-hydroxy-vitamin D3 (263 R1 = R4 = R5 = R6 = H, R2 = R3 = OH).123 Hydroxylation of the A bond of cholesta-l,5-dien-3/3-ol by means of 9-borabicyclo[3,3,l]nonane followed by reaction with alkaline hydrogen peroxide produced the 2-equatorial 2a,3a-diol in 70—80% yield. The conventional four-step sequence, acetylation, bromination, dehydrobromination, and hydrolysis, gave 2a -hydroxycholesta-5,7-dien-3/3-ol which was converted into 2a-hydroxy-vitamin D3. The isomeric 2/3-hydroxy-vitamin D3 has also been reported.124 Reaction of the 1/6,2/3-oxide obtained by peroxidation of the adduct (265) with lithium aluminium hydride results in a mixture of 2/3,3/3-dihydroxycholest-5,7-diene and its 1/3,3/3-dihydroxy-epimer in the ratio 8 1. Irradiation of the former 5,7-diene furnished the expected previtamin, which on equilibration gave 2/3-hydroxy-vitamin D3 (263 R1 = R4 = R5 = R6 = H, R2 = a-OH, R3 = OH). 

Palladium-catalyzed reaction of allylic 1,1-diol diacetate 136 with the pyrrolidino enamine of cyclohexanone (137) yields 2-acetoxybicyclo[3.3.1]nonan-9-one (138)68 (equation 25). 

There is however a second phenomenon decisively influencing the optical purities of the alcohols formed in the course of Penicillium citrinum catalyzed reduction.The formed alcohols are metabolized again this metabolization proceeds enantioselectively. The preferentially formed (S)-enantiomer is preferentially metabolized. As shown in Table III the optical purity (% enantiomeric excess, e.e.) of nonan-2-ol decreases from 92% e.e.(S) to 12% e.e. (S). Heptan-2-ol is finally present mainly as (R)-enantiomer. The metabolization steps are currently under investigation one of the pathways is a hydroxy-lation leading to hydroxy ketones and diols. Figure 5 presents structures of hydroxylated metabolites obtained from nonan-2-one. 

Dioxa-spiro[4.4 nonan 6-Brom-E14a/1, 221 (Keton/Diol/Br2)... 

---