Camphor, derivative

Ordinary commercial camphor is (-i-)-cam phor, from the wood of the camphor tree. Cinnamonum camphora. Camphor is of great technical importance, being used in the manufacture of celluloid and explosives, and for medical purposes, /t is manufactured from pinene through bornyl chloride to camphene, which is either directly oxidized to camphor or is hydrated to isoborneol, which is then oxidized to camphor. A large number of camphor derivatives have been prepared, including halogen, nitro and hydroxy derivatives and sulphonic acids. 

Asymmetric Oiels-Alder reaction, ene reaction, hydrogenation, halogenatlon by means of chiral olelln, such as camphor derivative 1 or 2. 

H2NOH-HC1, DABCO, MeOH, rt, 87% for a camphor derivative. This method was reported to be better than when pyridine was used as the solvent and base. 

Since cbiral sulfur ylides racemize rapidly, they are generally prepared in situ from chiral sulfides and halides. The first example of asymmetric epoxidation was reported in 1989, using camphor-derived chiral sulfonium ylides with moderate yields and ee (< 41%) Since then, much effort has been made in tbe asymmetric epoxidation using sucb a strategy without a significant breakthrough. In one example, the reaction between benzaldehyde and benzyl bromide in the presence of one equivalent of camphor-derived sulfide 47 furnished epoxide 48 in high diastereoselectivity (trans cis = 96 4) with moderate enantioselectivity in the case of the trans isomer (56% ee). ... 

Reagent-controlled aziridination using camphor-derived chiral sulfide 47 has been reported with ee values of 84-98% for the trans isomer although the tram cis ratio was... 

In recent years, several modifications of the Darzens condensation have been reported. Similar to the aldol reaction, the majority of the work reported has been directed toward diastereo- and enantioselective processes. In fact, when the aldol reaction is highly stereoselective, or when the aldol product can be isolated, useful quantities of the required glycidic ester can be obtained. Recent reports have demonstrated that diastereomeric enolate components can provide stereoselectivity in the reaction examples include the camphor-derived substrate 26, in situ generated a-bromo-A -... 

There has been some investigation of auxiliary-controlled cycloadditions of azir-ines. Thus, camphor-derived azirine esters undergo cycloaddition with dienes, with poor diastereoselectivity [70]. The same azirines were also observed to react unselectively with phenylmagnesium bromide. Better selectivities were obtained when Lewis acids were used in the corresponding cycloaddition reactions of 8-phe-nylmenthyl esters of azirine 2-carboxylates (Scheme 4.48) [71]. The same report also describes the use of asymmetric Lewis acids in similar cycloadditions, but mediocre ees were observed. 

Addilion of benzophenone to the lithium derivative 2 (M = Li) proceeds in a stereorandom fashion, which is attributed to the participation of radicals, detected by ESR and produced by single-electron transfer (SET)12. The magnesium derivative reacts with 90% diastereoselectivity with no SET being recorded. Benzaldehyde as the carbonyl compound affords the [1/, 1(1S)]-and [15,1(1/ )]-diastereomers in a 70 30 mixture, with 40% de12. Enhanced selectivities are achieved with camphor-derived 2-(2-oxazolyl)isoquinolines12a. 

The lithiation and hydroxyalkylation of camphor-derived A-benzylimines proceeds with medium-induced stereoselectivity15 16. 

Camphor derived acetates 1 (Helmchen-type65) and 3 (Oppolzer-lype66) add to aldehydes in a stereoselective manner when the Mukaiyama variation via the corresponding silylketene acetals is undertaken. Careful optimization of the reaction conditions provides predominantly... 

The asymmetric 1,4-addition of the dienolate of the optically active camphor derived 3-methyl-3-butenoate to 2-cyclopentenone gives a mixture of four diastereomers. The major adduct was applied in the synthesis of (—)-khusimone188. 

Optically active bicyclo[2.2,2]octanes can be obtained via diastercoselective MIMIRC reaction of lithium dienolates and a,/ -unsaturated esters of various chiral alcohols. Good yields (70-90%), high endo selectivities (> 95%) and diastereomeric ratios that depend on the auxiliary alcohol are found in these additions. The highest diastereomeric ratio reached was 18 82 using a camphor derived sulfonamide. The diastereomeric ratio could be improved (up to 9 91) by titanium(IV) chloride catalyzed addition of the corresponding silylenolates with the chiral a,/J-unsaturated esters358. 

In a conceptually similar fashion, camphor-derived hydroxysulfide 9 is oxidized diastereospecifically into hydroxysulfoxide 10 whose absolute configuration has been determined by X-ray crystallography48. Heating this diastereomer to 145 °C causes complete epimerization at sulfur to form diastereomer 11 in quantitative yield (equation 12). This type of allylic sulfoxide can be deprotonated and then added in a Michael fashion to cycloalkenones (see p. 834). 

Oligomers Oppolzer s camphor sultam (see also camphor derivatives) Organometallics Organosilicon Organosulfur Organozirconocenes Orthoquinodimethanes Oxabutadienes Oxanorbornadiene(s) Oxazinolactams Oxazinones Oxazoles... 

Imidazole and its derivatives continued to play an important role in asymmetric processes. Optically active pyrroloimidazoles 26 were prepared by the cycloaddition of homochiral imidazolium ylides with activated alkenes <96TL1707>. This reaction was used in the enantioselective preparation of pyrrolidines <96TL1711>. A review of the use of chiral imidazolidines in asymmetric synthesis was published <96PAC531> and the preparation and use of a new camphor-derived imidazolidinone-type auxiliary 27 was reported < 6TL4565> <96TL6931>. 

Scheme 1.33 Test reaction with (+ )-camphor-derived pyridine thioether ligand.

Camphor-derived disulfonamide ligand for additions of ZnEt2 aldehydes. 

In 2006, Wang et al. reported the synthesis of a new camphor-derived disulfonamide ligand based on L-tartaric acid that was employed in similar reactions to those described above, giving rise to enantioselectivities of up to 83% ee by using 5 mol% of catalyst loading (Scheme 3.43). ... 

Scheme 3.44 Ionic liquids containing camphor-derived sulfonamide ligand for addition of ZnEt2 to benzaldehyde.

Scheme 3.50 Camphor-derived A -sulfonylated amino alcohol ligand for additions of ZnEt2 to aldehydes.

Scheme 4.24 Addition of ZnEt2 to acetophenone with camphor-derived mesylamide ligand.

Scheme 9.8 Ir-catalysed reduction of acetophenone with camphor-derived amino sulfide ligands.

MeLi to cyclohexenone with p-amino sulfide ligand 88-9 MeMgl to acyclic enone with arene-thiolatocopper(l) complexes 90-1 mesylamide ligand (camphor-derived) 174, 176... 

ZnEt2 addition reactions to acetophenone withbis(snlfon-amides) diol ligand 157-8 to acetophenone with camphor-derived mesylamide hgand 174, 176... 

Camphor-derived sulfonamide can also permit control of enantioselectivity by use of additional Lewis acid. These chiral auxiliaries can be used under conditions in which either cyclic or noncyclic TSs are involved. This frequently allows control of the syn or anti stereoselectivity.143 The boron enolates give syn products, but inclusion of SnCl4 or TiCl4 gave excellent selectivity for anti products and high enantioselectivity for a range of aldehydes.145... 

A new chiral auxiliary based on a camphor-derived 8-lactol has been developed for the stereoselective alkylation of glycine enolate in order to give enantiomerically pure a-amino acid derivatives. As a key step for the synthesis of this useful auxiliary has served the rc-selective hydroformylation of a homoallylic alcohol employing the rhodium(I)/XANTPHOS catalyst (Scheme 11) [56]. 

A rich family of 2-alkoxycarbonyl-l,3,2-oxazaphospholidine-2-oxides 179-181 was prepared from the reaction of camphor derived aminoalcohols 177 and 178 with either methoxycarbonyl phosphonic dichloride or ethyl dichlorophosphite followed by the reaction with methyl bromoacetate. The reaction with aminoalcohol 177a afforded the phosphorus epimers 179 and 180, in ratios from 1/1 to 12/1 depending on the iV-substituent which could be separated easily by column chromatography. The reaction with aminoalcohols 178a-c, however, gave a single epimer 181a-c in each case (Scheme 50) [81]. 

Langlois synthesized (lS,5R)-44 by employing [3+2] cycloaddition between methyl methacrylate and camphor-derived oxazoline N-oxide (A) as the key-step (Scheme 66) [98]. 

Sulfur ylides are a classic reagent for the conversion of carbonyl compounds to epoxides. Chiral camphor-derived sulfur ylides have been used in the enantioselective synthesis of epoxy-amides <06JA2105>. Reaction of sulfonium salt 12 with an aldehyde and base provides the epoxide 13 in generally excellent yields. While the yield of the reaction was quite good across a variety of R groups, the enantioselectivity was variable. For example benzaldehyde provides 13 (R = Ph) in 97% ee while isobutyraldehyde provides 13 (R = i-Pr) with only 10% ee. These epoxy amides could be converted to a number of epoxide-opened... 

The binding of the diuretic amiloride 95 to DNA has been studied <06CC1185>. The chiral camphor-derived pyrazine ligand 96 showed monomeric coordination to Cu and Zn, in contrast to the bidentate polymeric behaviour of related earlier compounds <06ARK218>. 

Studies of the intramolecular cyclization of P-amino acids have included the use of camphor-derived oxazoline A-oxide 66 and a [3+2] cycloaddition reaction as a step in the formation of the amino acid with the required stereochemistry <00OL1053, OOEJOC1595>. A diastereoselective synthesis of a ip-methylcarbapenem intermediate utilises a cyclization of a P-amino acid <99CC2365>. 

However, most asymmetric 1,3-dipolar cycloaddition reactions of nitrile oxides with alkenes are carried out without Lewis acids as catalysts using either chiral alkenes or chiral auxiliary compounds (with achiral alkenes). Diverse chiral alkenes are in use, such as camphor-derived chiral N-acryloylhydrazide (195), C2-symmetric l,3-diacryloyl-2,2-dimethyl-4,5-diphenylimidazolidine, chiral 3-acryloyl-2,2-dimethyl-4-phenyloxazolidine (196, 197), sugar-based ethenyl ethers (198), acrylic esters (199, 200), C-bonded vinyl-substituted sugar (201), chirally modified vinylboronic ester derived from D-( + )-mannitol (202), (l/ )-menthyl vinyl ether (203), chiral derivatives of vinylacetic acid (204), ( )-l-ethoxy-3-fluoroalkyl-3-hydroxy-4-(4-methylphenylsulfinyl)but-1 -enes (205), enantiopure Y-oxygenated-a,P-unsaturated phenyl sulfones (206), chiral (a-oxyallyl)silanes (207), and (S )-but-3-ene-1,2-diol derivatives (208). As a chiral auxiliary, diisopropyl (i ,i )-tartrate (209, 210) has been very popular. 

The synthesis of camphor-derived nitrones (87), of spin traps containing alkyl-phenylphosphoryl (36a,b) (88) and diethoxyphosphoryl substituents (37-39) requires m-CPBA as an oxidant (Fig. 2.3) (89, 90). 

Knochel and coworkers synthesized a series of camphor-derived pyridine and quinoline P,N ligands. The catalysts 30 (Fig. 29.17) were used to hydrogenate substrates 1 and 2 in up to 95% and 96% ee, respectively [33]. The selectivities were moderate for other unfunctionalized alkenes however, a high enantioselec-tivity was reported for the hydrogenation of ethyl acetamidocinnamate 10 [34]. 

For acrylates, or type I reagents, applied in asymmetric Diels-Alder reactions, several chiral auxiliaries such as menthol derivatives, camphor derivatives,16,3 and oxazolidinones4 are available. Carbohydrate compounds have also been reported as chiral auxiliaries in a recent publication, although the stereoselectivity was not good.5 Here are examples in which asymmetric Diels-... 

Holton s Construction of the Polycyclic Ring. In Holton s synthesis,23 compound 97, which can be prepared from camphor derivatives, is the starting material. Hydroxy-directed epoxidation of compound 97 gives unstable compound 98, which fragments in situ to provide compound 99, thus furnishing the AB skeleton of taxol (Scheme 7-31).24... 

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