Tribromide, boron cyclization

Dimethyl-4-bromo-27/-chromenes are accessible via a boron tribromide induced cyclization of phenol derivatives 31 (Scheme 9). The reaction is proposed to proceed via O-deprotection and subsequent elimination of hydroxide to form the intermediate zwitterionic species 32. Addition of bromide, pyran ring closure and protonation provides 4-bromo-2/7-chromenes in moderate yield (Scheme 9) < 1997H(45) 1131 >. 

An improved procedure for the rapid synthesis of aryl dihydrobenzofurans with a boron tribromide-mediated cyclization was discussed and is shown below <03HCA343>. In the second total synthesis of diazonamide A, the late key step accounting for the dihydrobenzofuran formation was a DIBAL-H mediated lactam reduction and cyclization <03AG(E)1753>. 

An interesting cyclization is brought about in the two-step synthesis of compound 140 from the tribromide 141 (Scheme 56). The resolution of these complexes represents one of the first examples of optical resolution of triarylboranes. The crystal stmcture of 140b (R = Me, R = H) has been determined B-C distances are in the range 155.0-157.4 pm and the environment about the boron atom is close to trigonal-planar <1991TL6363>. 

The synthesis12 of indochrome A involved cyclization, catalyzed by boron tribromide, of the acyclic intermediate 242, treatment of the resulting deazauridine 243 with benzenediazonium chloride, hydrogenation of the product, and autoxidation of the resulting 5-ben-... 

Ether cleavage of 4-heptyl-3-methylveratrole 121 using boron tribromide affords 4-heptyl-3-methylcatechol 122 (Scheme 38). Oxidation of the catechol 122 with o-chloranil to 4-heptyl-3-methyl-l,2-benzoquinone 123 and subsequent immediate addition of aniline leads to 5-anilino-4-heptyl-3-methyl-l,2-benzo-quinone 124. Unlike the very labile disubstituted ort/zo-quinone 123, compound 124 is stable and can be isolated. Palladium(II)-mediated oxidative cyclization of the anilino-l,2-benzoquinone 124 provides carbazoquinocin C 51. 

The relay compound 1025 required for the synthesis of all of these 7-oxygenated carbazole alkaloids was obtained starting from commercially available 4-bromo-toluene (1023) and m-anisidine (840) in two steps and 72% overall yield. Buchwald-Hartwig amination of 4-bromotoluene (1023) with m-anisidine (840) furnished quantitatively the corresponding diarylamine 1024. Oxidative cyclization of 1024 using catalytic amounts of palladium(ll) acetate afforded 3-methyl-7-methoxycarbazole (1025). Oxidation of 1025 with DDQ led to clauszoline-K (98), which, on cleavage of the methyl ether using boron tribromide, afforded 3-formyl-7-hydroxycarbazole (99) (546) (Scheme 5.149). 

Oxindole 89 was cleanly demethylated upon treatment with boron tribromide. The resulting oxindole 90 was subjected to the prenylation conditions, and the desired alkylated product 91 was obtained in 52% yield. The epoxidation/Lewis acid-mediated cyclization proved to be successful on this substrate. The epoxide product was directly treated with SnCl4 in THF to provided the desired 92. When oxindole 92 was treated with NaBHt (1.6 equivjand BF3 OEt2 (3.5 equiv) in THF, the desired 93 was obtained. The indole 93 was treated with TBDMSC1 and imidazole in DMF, to provide the required O-silylated indole, which was easily converted to the gramine 94 through the well known Mannich procedure. 

The dithiane derivative 60 (Scheme 14) is such a compound, it being made from 2,3 5,6-di-0-isopropylidene-D-mannose by treatment with 2-lithio-l,3-dithiane to give a heptose dithioacetal that was refunctionalized at C-2-C-3 by way of the C-l anion and then converted to the 6,7-epoxide following selective acid-catalyzed cleavage of the 6,7-acetal ring. Treated with n-butyllithium it gives, in 70% yield, the cyclized 61, which is efficiently convertible into validatol 62, a component of validamycin A, by desulfurization with Raney nickel and de-O-protection by use of boron tribromide in dichloromethane [31]. 

The /3-aminoester 385, synthesized by coupling of a chiral imine with a ketene acetal, cyclized toward cis-3-hydroxy-4-phenylazetidin-2-one 386 in the presence of boron tribromide (Scheme 57) <1998BML1619>. 

Cyclization of enone (9) in hexane with boron trifluorideetherate in presence of 1,2-ethanedithiol, followed by hydrolysis with mercury (II) chloride in acetonitrile, yielded the cis-isomer (10) (16%) and transisomer (11) (28%). Reduction of (10) with lithium aluminium hydride in tetrahydrofuran followed by acetylation with acetic anhydride and pyridine gave two epimeric acetates (12) (32%) and (13) (52%) whose configuration was determined by NMR spectroscopy. Oxidation of (12) with Jones reagent afforded ketone (14) which was converted to the a, 3-unsaturated ketone (15) by bromination with pyridinium tribromide in dichloromethane followed by dehydrobromination with lithium carbonate and lithium bromide in dimethylformamide. Ketone (15), on catalytic hydrogenation with Pd-C in the presence of perchloric acid, produced compound (16) (72%) and (14) (17%). The compound (16) was converted to alcohol (17) by reduction with lithium aluminium hydride. 

Intramolecular acylations of pyrroles and indoles are useful synthetically, for example, A-glutamyl-substituted pyrrole 94 gives 95, regioselectively, with retention of configuration, on brief treatment with methanolic hydrogen chloride or boron tribromide. A seven-membered ketone 97 was produced from 96 no cyclization onto the indole 4-position was observed <1999T4341>. 

A new synthesis of dibenzoboroles by reductive cyclization of arylboron dibromides opens up access to several derivatives of this ring system (Scheme 6) <1996JA7981>. MonoaryIboron dibromides 61 and 62 were prepared by reaction of the appropriate aryl lithium compound 60 with boron tribromide in hexane. Reductive cyclization of arylboron dibromide 61 with an excess of lithium metal in diethyl ether gave bislithium dibenzoborole complex 63. At the time of writing, compound 63 was the first dibenzoborole dianion to be structurally characterized by X-ray... 

Quinazolinones 1 bearing a methoxy substituent in the benzene ring, readily obtained by cyclization of the appropriate precursors (cf. Section 6.3.1.1.1.), are transformed into the corresponding hydroxyquinazolinones 2 on treatment with hydrobromic acid, - hydriodic acid, aluminum trichloride,or boron tribromide. Similarly, quinazoline-2,4-diamines bearing a methoxy group at position 6 or 8 are demethylated with boron tribro-mide in dichloromethane, sodium methanethiolate in dimethylacetamide or by pyridini-um hydrochloride fusion at 200... 

These two milestone syntheses were soon followed by others, and activity in this field continued to be driven by interest in the biologically active esters of cephalotaxine. In 1986, Hanaoka et al. (27) reported the stereoselective synthesis of ( )-cephalotaxine and its analog, as shown in Scheme 4. The amide acid 52, prepared by condensation of ethyl prolinate with 3,4-dimethoxyphenylacetyl chloride, followed by hydrolysis of the ethyl ester, was cyclized to the pyrrolobenzazepine 53 by treatment with polyphos-phoric acid, followed by selective O-alkylation with 2,3-dichloropropene (54) in the presence of sodium hydride. The resulting enol ether 55 underwent Claisen rearrangement on heating to provide C-allylated compound 56, whose reduction with sodium borohydride yielded the alcohol, which on treatment with 90% sulfuric acid underwent cationic cyclization to give the tetracyclic ketone 57. Presumably, this sequence represents the intramolecular version of the Wichterle reaction. On treatment with boron tribromide, ketone 57 afforded the free catechol, which was reacted with dibromometh-ane and potassium fluoride to give methylenedioxy derivative 58, suited for the final transformations to cephalotaxine. Oxidation of ketone 58... 

Intramolecular reaction with nucleophilic groups can also lead to heterocycles. For example, good yields of 3-acylbenzofurans result from cyclization caused by intramolecular substitution of the tertiary amino group by a phenol formed by cleavage of a phenol ether by boron tribromide (equation 182). o-Hydroxybenzyl alcohols were used to obtain 4 f-chromenes by their reaction with 4-morpholino-3-buten-2-one in acetic acid-acetic anhydride . 

The utility of the RBR in the synthesis of crovrded trisubstituted alkenes is demonstrated by the synthesis of ampelopsin D (Scheme 8.201. The thioether 48 was generated by acid-promoted cyclization of alcohol 46 and attack by thiol 47 on the benzylic cation. This conpound had a trans-relationship between the aryl branches on the indane system and was produced as a 1 1 mixture of epimers at the thioether linkage. In preparation for the RBR, the thioether 48 was oxidized to sulfone 49, which was treated with base and carbon tetrachloride to produce the RBR product 50 in 52% yield, along with 15% of its (Z)-isomer. Meyers conditions were found to be optimal for stereoselectivity in the RBR, with other methods producing poorer selectivity and unreliable results. The natural product ampelopsin D (51) was obtained after global deprotection with boron tribromide. 

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