Temperature-selective diastereo

FIGURE 56.8. Temperature-selective diastereo-recognition (TSD) enantiomeric ibuprofen via environmentally benign selective crystallization. 

THPB tetrahydroprotoberberine Trt trityl tosyl (para-toluenesulfonyl) temperature-selective diastereo-... 

The lipase-catalyzed resolution of (2/ , 35 )-3-methyl-3-phenyl-2-aziridine-methanol ( )-H by using the low-temperature method gave synthetically useful (2/ ,35 )-ll and its acetate (2S, iR)- a with (25 )-selectivity E = 55 at —40°C), while a similar reaction of (2/ , 3f )-3-methyl-3-phenyl-2-aziridinemethanol ( )-12 gave (25,35 )-12 and its acetate (2/ ,3/ )-12a with (2/ )-selectivity E = 73 at —20°C) (Scheme 2). Compound ( )-ll was prepared conveniently via diastereos-elective addition of MeMgBr to t-butyl 3-phenyl-2//-azirine-2-carboxylate, which was successfully prepared by the Neber reaction of oxime tosylate of t-butyl... 

The regio- and diastereo-selectivity of the Michael addition of 2-phenylcyclo-hexanone with a,p-unsaturated ketones are dependent on the reaction conditions. Mixtures of all six diastereoisomers resulting from reaction at either the 2- or 6-position of the cyclohexanone ring can be obtained using solid potassium hydroxide with tetra-n-butylammonium or A-benzylephcdrinium bromide catalysts. At 20°C with tetra-n-butylammonium bromide, the ratio of the 2,2- and 2,6-disubstituted cyclohexanones is ca. 3 2, but at higher temperatures with solid potassium f-butoxide the kinetically formed 2,6-isomer predominates (ca. 5 1) with the (2S,6R, R )-stereoisomer dominant, whereas greater amounts of the thermodynamically preferred 2,2-(2S,lR )-isomer are obtained with the chiral catalyst [61]. 

In contrast to the solution photochemistry, irradiation of the crystals of le provided remarkably high diastereoselectivities in the formation of 2e. The temperature at which the reaction occurs is important in determining dia-stereoselectivity. At 15 °C, the de of syn-2e was 61 % and the ratio of syn/anti was 8.7, which was the reverse of that in the solution reaction (syn/anti=0.9). The solid-state photoreaction proceeded even at -78 °C, and with higher diastereo-selectivity. At low conversion (9%), only syn isomers (de=93%) were obtained, and 71% de was observed even at 90% conversion. 

Regio- and diastereo-selective methoxyselenenylation of cinnamylamines attached (g) to a chiral perhydrobenzoxazine (17) proceeds in high yields in dichloromethane-methanol. The diastereoselection is dependent on the temperature and the nature of the substituent at C(2) and can be rationalized by accepting a 1,4-asymmetric induction process after coordination of the selenium to the nitrogen atom of the allylamine... 

Alkyl and aryl sulfides RSH react with equimolecular amounts of p-toluenesulfonyl-acetylene, HC C-SC Tol, in CH3CN at 0 °C or room temperature in the absence of any catalytic reagent to give Z-adducts RS-CH=CH-S02Tol with total diastereo-selectivity. On the other hand, in the presence of 1.1 equiv. of NaH in THF, the same reaction affords the corresponding li-diastereoisomers also with total diastereoselec-tivity.211... 

The use of a chiral fumarate ester allows for asymmetric induction irrespective to the approach of the dienophile to the diene. In particular, dimenthyl fumarate (6) has been advocated for large scale because of its ready availability, low cost, excellent yields, and high asymmetric induction.35128129 203-208 Although other more exotic chiral auxiliaries may be used,32 the use of 5 coupled with a homogeneous Lewis acid catalyst at low temperatures allows for remarkably high diastereo-selectivity with a number of dienes (Scheme 26.5).125 164-209... 

Until recently organic photochemistry has only partially focused on stereoselective synthesis, one of the major challenges and research areas in modern organic synthesis. This situation has dramatically changed in the last decade and highly chemo-, regio-, diastereo- as well as enantioselective reactions have been developed. Chemists all over the world became aware of the fascinating synthetic opportunities of electronically excited molecules and definitely this will lead to a new period of prosperity. Photochemical reactions can be performed at low temperatures, in the solid or liquid state or under gas-phase conditions, with spin-selective direct excitation or sensitization, and even multi-photon processes start to enter the synthetic scenery. 

Whereas cyclic secondary enaminones and nitroolefins mainly yield indoles in which the enamine nitrogen is incorporated into the heterocyclus (equation 242), linear tertiary a-ketoenamines are shown to react with nitroolefines at low temperature under kinetic control to give 1,2-oxazine N-oxides as [4 + 2]-cycloadducts, followed by retro-Diels-Alder reaction or rearrangement under thermodynamic control which leads diastereo-selectively to aminocyclopentenes. The reaction is called [3 + 2]-carbocyclization, apparently because the ketoenamine is reacting as a 1,3-dipole. The products are hydrolysable to polysubstituted nitrocyclopentanones with retained configuration325 (equation 243). 

The imidazolines (107) and (108) reacted with nitrile oxides with modest to high stereoselectivity, but low regioselectivity (91BCJ3274). Diastereo-selective reactions of the oxazolidines (109) and the imidazoline (110) have also been reported (91BCJ3274,91TA1185). As a representative example, the imidazoline (110) reacted with benzonitrile oxide (3) at room temperature to give the adducts (111) and (112) in the ratio 4 1. After separation... 

Where no assistance can be expected from intramolecularity, or from a reactive rearomatizing o-qui-nodimethane system as above, [4 + 2] cycloadditions with inverse electron demand are required. Thus, reaction of the 2-aza-1,3-butadiene (146) with the electron-rich enamine (147) at room temperature affords the octahydroisoquinoline (148) in high regio- and diastereo-selectivity (Scheme 68). ... 

Furyl derivatives 76, with an allylether or allylamine-type linkage to a methylenecyclopropane framework, readily undergo high pressure-promoted intramolecular cycloaddition" to give spirocyclopropane tricyclic products 77. No cycloaddition reaction occurred at ambient pressure and the products were mostly tar and polymers. Lewis acid catalysis was only marginally successful (Scheme 7.18). At 1.0 GPa and a slightly elevated temperature (60-70 °C) the intramolecular Diels-Alder reaction occurs readily and is exo-diastereo-selective. To quantify the pressure effect on the kinetics the volumes of activation were determined. 

The allylation of aldehydes with allylstannanes is effected with Lewis acids such as boron trifluoride etherate or titanium(IV) chloride (eq (104)) [99], in which diastereo-selectivity is dependent on the catalyst employed the most striking feature is that. n77-homoallyl alcohols are stereoselectively produced using boron trifluoride etherate. Although this allylation occurs without a catalyst, high reaction temperature must be used. 

Independently, Davies et al.l also reported the same approach as descrihed above hy Winkler et al. The Rh2(S-DOSP)4-catalyzed decomposition of methyl phenyldiazoacetate (40) in the presence of WBOC-piperidine (41, 4 equivalents) in 2,3-dlmethylbutane at room temperature, followed by treatment with tri-fluoroacetic acid, resulted in the formation of a mixture of threo- and e/yZftro-methylphenidate in 49% yield. However, the Zftreo-isomer was the minor diastereomer and was formed in only 54% ee. A major improvement in enantioselectivity and diastereo-selectivity was achieved hy carrying out the reaction with the Rh2(S-biDOSP)2 catalyst. The ratio of threo to erythro isomers was improved to 2.5 1 (75% yield), respectively. The (27 ,2 7 )-Z/ireo-isomer was formed in 86% ee and isolated in 52% yield. 

Using tryptamine as the nucleophile, the Michael addition-cyclization strategy was extended to the enantioselective synthesis of the /J-carboline alkaloid system. Michael addition of tryptamine to the chiral acetylenic sulfoxides took place smoothly at room temperature. Either trifluoroacetic acid or p-toluene-sulfonic acid was effective as a catalyst for the cyclization step (Scheme 7). The results of the Michael addition-cyclization reaction sequence are summarized in Table 3. In general, we found that the indole moiety is more reactive than the dimethoxyaryl ring used in the tetrahydroisoquinoline synthesis. Therefore, the cyclization step could take place at a temperature as low as -60 °C. Also, p-tolu-enesulfonic acid resulted in a better diastereoselectivity. However, the diastereo-selectivity of the system is much less sensitive to the aryl substituents of the acetylenic sulfoxides compared to that of the tetrahydroisoquinoline system. Also, to our surprise, the steric factor on the chiral acetylenic sulfoxide has little effect on the diastereoselectivity. Even with the bulky 2-methoxy-naphthyl acetylenic sulfoxide lc [11], the diastereoselectivity still remained roughly the same as for 1 a and 1 b (Scheme 7) (Table 3). 

Frequently, the differences in entropy between two diastereomeric transition states are small, and the enthalpy term predominates. However, the entropy term cannot always be neglected, and sometimes it may even dominate according to the reaction conditions [2], In some cases, the observed selectivity can be inverted by changing the temperature of the reaction, and the temperature at which AAH = TAAS is called the isokinetic temperature (isoinversion). The occurrence of an isokinetic temperature in the normal operating range is not veiy frequent, but it is observed sometimes in multistep processes (see below). The ratio of the diastereo-isomeric products formed in kinetically controlled reactions is given by the relationship... 

In order to impart a higher crystallinity and reactivity to the dienophile, acryloyl and crotonoyl sultams 20a and b, readily prepared from ( + )- or (—)-camphor-10-sulfonyl chloride, were designed 5. In the presence of chelating Lewis acids, excellent diastereo- and endo selectivity, as well as good chemical yields, are obtained for a range of dienes and dienophiles at low temperatures. 

Several examples of the 1,3-dipolar cycloadditions between nitrones and 3-(2-alkenoyl)-l,3-oxazolidin-2-ones using the novel hetero-chiral Yb(III) catalyst are shown in Table 32. In most cases, the desired isoxazolidine derivatives were obtained in excellent yields with excellent diastereo- and enantioselectivities. It is noted that high levels of selectivities were attained at room temperature. Nitrones derived from aromatic and heterocyclic aldehydes gave satisfactory re-... 

---