Diisobutylaluminum hydride reductive cyclization

Perlmutter used an oxymercuration/demercuration of a y-hydroxy alkene as the key transformation in an enantioselective synthesis of the C(8 ) epimeric smaller fragment of lb (and many more pamamycin homologs cf. Fig. 1) [36]. Preparation of substrate 164 for the crucial cyclization event commenced with silylation and reduction of hydroxy ester 158 (85-89% ee) [37] to give aldehyde 159, which was converted to alkenal 162 by (Z)-selective olefination with ylide 160 (dr=89 l 1) and another diisobutylaluminum hydride reduction (Scheme 22). An Oppolzer aldol reaction with boron enolate 163 then provided 164 as the major product. Upon successive treatment of 164 with mercury(II) acetate and sodium chloride, organomercurial compound 165 and a second minor diastereomer (dr=6 l) were formed, which could be easily separated. Reductive demercuration, hydrolytic cleavage of the chiral auxiliary, methyl ester formation, and desilylation eventually led to 166, the C(8 ) epimer of the... 

The crucial cyclization of 129 was accomplished by oxidation with pyri-dinium chlorochromate (PCC) and acetylation, providing two cyclohexane derivatives (130 and 131) in the ratio of 10 1. Thermal decarboxylation of 130 resulted in formation of the cyclohexene derivative 132, with concomitant elimination. Reduction of the ester group with diisobutylaluminum hydride converted 132 into 133. Hydroboration-oxidation of 133 gave the carba-sugar derivative 134 as a single product. 

Vertaline (61) was synthesized through two routes that involve an W-acylimin-ium ion cyclization (20) and an intermolecular [3 + 2] cycloaddition (21,22) as the key steps, respectively. Model studies (20, 24) for assembling the quinolizi-dine moiety by the W-acyliminium ion cyclization are shown in Scheme 7. The benzyl alcohol 65 was converted to glutarimide 66 by the Mitsunobu procedure in 55% yield. Reduction of imide 66 with diisobutylaluminum hydride afforded 67, which was subjected to V-acyliminium cyclization to give the lactam 68 in 40% overall yield from 66. Lactam 68 possesses the correct stereochemistry at all chiral centers required for vertaline (61). 

Synthesis of P-Keto Sulfoxides. Optically active p-keto sulfoxides are very useful building blocks (eq 4) because they can be stereoselectively reduced to afford either diastereomer of the corresponding p-hydroxy sulfoxide under appropriate conditions (Diisobutylaluminum Hydride or Zinc ChloridefDlBALf and thus give access to a wide variety of compounds chiral carbinols by desulfurization with Raney Nickel or LithiumJethyhmme ini the case of allylic alcohols epoxides via cyclization of the derived sulfonium salt butenolides by alkylation of the hydroxy sulfoxide 1,2-diols via a Pummerer rearrangement followed by reduction of the intermediate. ... 

A more stereoselective reaction was seen in the ring closure of 7-silylthiol 70 (91) (eq. [53]). Since diisobutylaluminum hydride is known to cause reduction with complete retention at silicon (146), the intramolecular cyclization of ( )-(-)-70 must occur with at least 90% retention of configuration. 

In two separate routes the aminoepoxides were obtained by highly stereoselective methods. Chlorination of iV -benzoylquinotoxine (5) with iV -chlorodiisopropylamine in 100% phosphoric acid in the dark gave an amorphous mixture of the epimeric a-chloroketones 85 and 86 (Scheme 8) [10). Reduction with sodium borohydride or with lithium tri-i-butoxyaluminum hydride afforded stereoselectively a mixture of the threo chlorohydrins 87 and 88. Treatment of 87 and 88 with aqueous potassium hydroxide at 20°C gave smoothly a mixture of the erythro iV-benzoylepoxides 89 and 90. The benzoyl groups were removed reductively with diisobutylaluminum hydride to give the aminoepoxides 81 and 82 which were cyclized in refluxing toluene-methanol (100 1). This reaction yielded 9-ep -quinine (12) and 9-epi-quinidine (13) in a ratio of 2 1. The overall yield of 12 and 13 from 87 and 88 was 50%. Only traces of the erythro products quinine and quinidine were observed. 

Chiral 1,2,3,4-tetrahydroisoquinolines are accessible from 0-carbamyl lactates via N-oxaacyliminium cyclization (Scheme 31). The precursor for the generation of the chiral N-oxaacyliminium ion 220 is prepared by reaction of (5)-methyl lactate (97) with azide 217 followed by partial reduction of 218 with diisobutylaluminum hydride. Cyclization of 219 with formic acid at room temperature for 14 h gives the oxazolo[4,3- 2]isoquinoline (221) without racemization [78]. Reductive cleavage of the oxazoline ring with lithium aluminum hydride furnishes the corresponding l-hydroxyalkyl-l,2,3,4-tetrahydroisoquinoline in 98% yield. 

Peltier and Ellman reported on an asymmetric synthesis of 2,4,6-trisubstituted piperidines 258 with excellent stereoselectivity. The starting chiral sullinamide 255 was prepared by the Michael addition of ketimine and a,(3-unsaturated ketone. Treatment of 256 with L-Selectride followed by Dess-Martin periodinane (DMP) oxidation produced iy -A7-sulfinylamino ketone 257 with a high diastereomeric ratio, whereas NaBH4-Ti(OEt)4 reduction of 256 followed by DMP oxidation afforded the anti isomer of 258 with 87 13 diastereomeric ratio. 257 underwent alkylative cyclization by acidic treatment followed by diisobutylaluminum hydride (DIBt L-H) reduction to afford 2,4,6-trisubstituted piperidines 258 with excellent diastereoselectivity (Scheme 40.57). 

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