Reductions intramolecular

An unusual solvent system was chosen for the intramolecular reductive alkylation of the masked amino ketone (15). The purpose of the strongly acid system was to prevent cyclization of the deblocked amino ketone to 16, further hydrogenation of which gives the unwanted isomer 17 by attack at the convex face. The desired opposite isomer can be obtained by reduction of 16 with UAIH4 (52). 

One-electron oxidation of the Fe(IIl) complexes Fe(Por)R can either give an observable Fe(lV) complex, [Fe(Por)R]", or can induce migration of the R group to a pyrrole nitrogen, essentially an intramolecular reductive elimination process. 

Scheme 8 Intramolecular reductive coupling of a planar chiral diimine...

Scheme 24 Titanium-mediated intramolecular reductive cyclopropanation of N-aUyl-a-amino acid dimethylamides...

Motherwell and Whitehead et al. reported a similar intramolecular reductive aldol reaction of aldehyde-enoate derivatives. The cyclization of 6-oxo-ester 23 was catalyzed by RhCl(PPh3)3 (1 mol%) with Et3SiH (210 mol%) as terminal reductant (Scheme 9) [17,18]. The cyclization proceeded at 50 °C for 18 h to give the aldol product 24 in 81% yield with ds-selectivity (cis trans =... 

Scheme 9 Rh-catalyzed intramolecular reductive aldol reaction of 6-oxo-hex-2-enoates...

The intramolecular reductive aldol reaction of keto-enones was successfully conducted under conditions similar to those described above, employing a cationic Rh complex and PI13P (Scheme 20) [34]. The keto-enone 63 was cyclized in the presence of added K2CO3 to give the ketone-aldol 64 in 72% yield with exclusive ds-selectivity. Dione-enone derivatives, for example 68 and 70, were efficiently cyclized to furnish bicyclic aldol products 69 and 71, respectively, wherein three stereogenic centers of the bicyclic product form stereoselectivity through the intermediacy of a Rh-enolate. 

Copper hydride species, notably Stryker s reagent [Ph3PCuH]6, are capable of promoting the conjugate reduction of a,( >-unsalurated carbonyl compounds [42], Taking advantage of this trustworthy method, Chiu et al. demonstrated in 1998 an intramolecular reductive aldol reaction in the synthesis of novel terpenoid pseudolaric acids isolated from Chinese folk medicine (Scheme 28) [43]. Two equivalents of [Ph3PCuH]6 enabled cycli-zation of keto-enone 104 to provide the bicyclic diastereomers 105 (66%) and 106 (16%). The reaction also was applied to the transformation of 107... 

Scheme 28 Intramolecular reductive aldol reaction promoted by stoichiometric Stryker s...

Scheme 5 Ni-EtjSiH promoted intramolecular reductive coupling of 15...

Scheme 16 Intramolecular reductive homoallylation of a>dienyl aldehydes...

The formation of these compounds has been rationalized according to Scheme 6. The reaction of Os (E )-CH=C 11 Ph C1 (C())( P Pr3)2 with n-BuLi involves replacement of the chloride anion by a butyl group to afford the intermediate Os (/i> CH=CHPh ( -Bu)(CO)(P Pr3)2, which by subsequent hydrogen (3 elimination gives OsH ( >CI I=CHPh (CO)( P Pr3)2. The intramolecular reductive elimination of styrene from this compound followed by the C—H activation of the o-aryl proton leads to the hydride-aryl species via the styrene-osmium(O) intermediate Os r 2-CH2=CHPh (CO)(P Pr3)2. In spite of the fact that the hydride-aryl complex is the only species detected in solution, the formation of OsH ( )-CH=CHPh L(CO)(P Pr3)2 and 0s ( )-CH=CHPh (K2-02CH)(C0)(P,Pr3)2 suggests that in solution the hydride-aryl complex is in equilibrium with undetectable concentrations of OsH ( )-CH=CHPh (CO)(P,Pr3)2. This implies that the olehn-osmium(O) intermediate is easily accessible and can give rise to activation reactions at both the olefinic and the ortho phenyl C—H bonds of the... 

Conjugated nitrones are formed by intramolecular reductive cyclizations of nitro groups onto ketones the resulting nitrones give starting materials for preparing azasteroids. An example is shown in Eq. 8.43.66... 

Piperidines bearing a masked aldehyde function in the e-position are easily transformed into quinolizidine compounds through intramolecular reductive amination after deprotection (acetal precursors) or oxidative cleavage (tv e-diols). Some examples are given below. 

V-( 1,1 -dimcthylbut-3-cnyl)-hydroxylamine followed by intramolecular 1,3-dipolar cycloaddition, was easily converted into the polyhydroxylated quinolizidine 192 by removal of the isopropylidene group and hydrogenolysis of the N-O bond in the presence of Raney-nickel accompanied by intramolecular reductive amination (Scheme 35) <2001CC915>. 

Protected pyrazoline derivatives 429 can be transformed by conventional ozonolysis methodology to the corresponding aldehydes 430, then the Cbz protecting group is removed and the intramolecular reductive amination using... 

A third method for the synthesis of cycl[3.2.2]azines, from iV-(aroylmethyl)pyridinium salts via indolizines, involves intramolecular (reductive) McMurry coupling of the latter. For example, 3,5-dibenzoylindolizines, obtained from 2-benzoyl-iV-phenacylpyridinium bromide as shown (Scheme 91), are cyclized using zinc and titanium(iv) chloride to give the 3,4-diphenylcyclazines 352 in high yield (>90%). The reaction cannot be applied, however, to... 

The grem-dibromocyclopropanes 152 bearing a hydroxyalkyl group, prepared by the addition of dibromocarbene to allylic or homoallylic alcohols, undergo an intramolecular reductive carbonylation to the bicyclic lactones 153. bicyclic lactone derived from prenyl alcohol is an important precursor for the synthesis of ris-chrysanthemic acid. (Scheme 54)... 

Xie and co-workers developed a simple route for the synthesis of 3-aryl-l,2,3,4-tetrahydroquinolines 79 using a direct intramolecular reductive ring closure strategy <06TL7191>. The yields for the key reductive ring closure were moderate however, the simplicity of their route leads to an efficient synthesis of a variety of tetrahydroquinolines 79. 

S ilylation-intramolecular reduction, ketone-alcohol reduction, 78-79 Single-electron transfer (SET) process, alkyl halides and triflate reduction to alkanes, 28-31... 

Intramolecular reductive cross-coupling of unsymmetrical dibenzylidene sulfamides 149 generated the corresponding cyclic sulfamides 150 in good yield (Scheme 23) <1996TL2859>. 

One of the most convenient ways to form benzocinnolines 183 is the intramolecular reductive coupling of 2,2 -dinitrobiphenyls 182 exemplified by the work of Kaszynski and Sandhu <00JCS(P1)67>. The reaction is general, effected by most typical reducing agents with good to excellent yields . 

Krische and co-workers have revealed efficient reductive generation of rhodium enolates under hydrogenation conditions.403 40311-403 Both inter- and intramolecular reductive aldol reactions proceed smoothly and stereoselec-tively, although intermolecular reactions generally show low diastereoselectivity (Equations (52) and (53)). 

Diene, intramolecular, reductive Only Ni(0) 427,427a,427c,427e-427g... 

For use of conjugated enones as nucleophilic partners in catalytic intramolecular reductive couplings to aldehydes, see ... 

Xenovinine 195, a natural alkaloid, was obtained by catalytic hydrogenolysis of carbamate 194 and subsequent intramolecular reductive amination of the in /-////-generated A-deprotected ketopyrrolidine <1999T8915>. Enantiodivergent synthesis of 195 with the same reductive amination as final step was also reported (Scheme 45) <1998EJO 955>. 

Catalytic reduction (Raney-Ni, H2) of the nitroso acetal-mesylate 243 resulted in reductive cleavage of both N-O bonds followed by intramolecular reductive amination and finally intramolecular iV-alkylation providing the masked 7-epiaustraline alkaloid 244 (Scheme 65) <1998JA7357>. 

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