Rhodium octanoate

In the Sepracor synthesis of chiral cetirizine di hydrochloride (4), the linear side-chain as bromide 51 was assembled via rhodium octanoate-mediated ether formation from 2-bromoethanol and ethyl diazoacetate (Scheme 8). Condensation of 4-chlorobenzaldehyde with chiral auxiliary (/f)-f-butyl sulfinamide (52) in the presence of Lewis acid, tetraethoxytitanium led to (/f)-sulfinimine 53. Addition of phenyl magnesium bromide to 53 gave nse to a 91 9 mixture of two diastereomers where the major diasteromer 54 was isolated in greater than 65% yield. Mild hydrolysis conditions were applied to remove the chiral auxiliary by exposing 54 to 2 N HCl in methanol to provide (S)-amine 55. Bisalkylation of (S)-amine 55 with dichlonde 56 was followed by subsequent hydrolysis to remove the tosyl amine protecting group to afford (S)-43. Alkylation of (5)-piperizine 43 with bromide 51 produced (S)-cetirizine ethyl ester, which was then hydrolyzed to deliver (S)-cetirizine dihydrochloride, (5)-4. 

In CHEC-II(1996), carbene insertion reactions into the N-H bond to form a fused-ring azetidinone warranted a separate section. In the last decade, the popularity to this approach to bicyclic systems seems to have markedly declined. Nevertheless, dirhodium tetraacetate and rhodium octanoate were used to generate the corresponding bicyclic compounds from the diazo compounds 241 (R2 = H and /3-Me), respectively, via the carbene intermediates. In the latter case, the produced enol was esterified and then the ester group replaced with a hydroxymethyl substituent to give derivatives 242 in a one-pot process <2001JCM166, 1999TL427>. 

In the Sepracor synthesis of chiral cetirizine dihydrochloride (4), the linear side-chain as bromide 51 was assembled via rhodium octanoate-mediated ether formation from 2-bromoethanol and ethyl diazoacetate (Scheme 8). Condensation of 4-... 

Rhodium-catalysed cyclization of oc-diazoacylanilines to 3-acetylindol-2-ols can give high yields. Rhodium octanoate, followed by chlorodiphenyl phos-... 

The first total synthesis of the intricate Stemona alkaloid (+ /—)-isostemofoline (224) was reported by Kende and coworkers 81) starting from 1,2-hexanediol (225) which was straightforwardly converted to 227 (Scheme 22) 82). Reductive cycUzation with sodium hydrosulfite in refluxing aqueous ethanol, and protection of the unstable pyrrole as tert-butyl carbamate, afforded 228 in five steps with 12% overall )deld. The key bicyclic ketone 231 was assembled by [4 + 3] cycloaddition of pyrrole 228 and diazoester 229 promoted by rhodium octanoate dimer, followed by enol silane deprotection, exo-specific hydrogenation, and nucleophilic decarboxylation (47% overall yield). Sodium methoxide-catalyzed aldol condensation of ketone 231 and furfural provided the Q-j/i-unsaturated ketone 232 whose olefin configuration was established by nOe studies. Allylation of 232 provided a 2.4 1 mixture of ketone 234 and the corresponding allylic enol ether 233, which could be converted to the former via a stereoselective Claisen rearrangement. 

Scheme 22. Reagents and Conditions (i) aq. NaOCl, HOAc (65%) (ii) MOMCl, /-Pr2NEt, CH2CI2, 0°C to rt (93%) (iii) Me2NN=CHCHO, KOEt (80%) (iv) Na2S204, EtOH, H2O, 90°C (35%) (v) (Boc)20, DMAP, CH3CN (72%) (vi) 229, rhodium octanoate dimer, pentane, reflux (90%) (vii) BU4NF, THE (65%) (viii) H2, 5% Pd/C, MeOH (90%) (ix) H2O, DMSO, 150°C (90%) (x) furfuraldehyde, NaOH, MeOH, H2O, reflux (90%) (xi) LiHMDS, DMPU...

The formation and intramolecular dipolar cycloaddition of azomethine ylides formed by carbenoid reaction with C=N bonds has recently been studied by the authors group.84 Treatment of 2-(diazoace-tyl)benzaldehyde O-methyl oxime (176) with rhodium(II) octanoate in the presence of dimethyl acetylenedicarboxylate or N-phenylmaleimide produced cycloadducts 178 and 179, respectively. The cycloaddition was also carried out using p-quinone as the dipolarophile. The major product isolated corresponded to cycloadduct 180. The subsequent reaction of this material with excess acetic anhydride in pyridine afforded diacetate 181 in 67% overall yield from 176. The latter compound incorporates the basic dibenzofa, d -cyclohepten-5,10-imine skeleton found in MK-801,85 which is a selective ligand for brain cyclidine (PCP) receptors that has attracted considerable attention as a potent anticonvulsive and neuro-protective agent.86,87... 

The formation and intramolecular dipolar cycloaddition of azomethine ylides formed by carbenoid reaction with C-N double bonds has recently been studied by the author s group [66]. Treatment of 2-(diazoacetyl)benzaldehyde O-methyl oxime (118) with rhodium (II) octanoate in the presence of dimethyl acetylenedicarboxylate or iV-phenylmaleimide produced cycloadducts 120 and... 

Rhodium(II) octanoate-catalyzed decomposition of the vinyldiazomethane 190 in refluxing hexane in the presence of iV-Boc-pyrrole results in the formation of tropanes 191, the products of a tandem 2,3-cyclopropanation/Cope rearrangement <1991JOC5696, 1995TL7205>. 

Side reactions became even more prevalent when 2-methyl-A -BOC-pyrrole 1046 was used as substrate (the addition of the methyl group increased the electronic density on the pyrrole and this led to enhanced formation of products derived from zwitterionic intermediates) (Equation 247). Thus, rhodium(ll) octanoate-catalyzed decomposition of diazoalkane 1042 in the presence of pyrrole 1046 resulted in the formation of three types of products two isomeric tropanes, 1047 (38% and 56% for R = Me and R = EtC02CH2, respectively) and 1048 (16% and 8% for R = Me and R = EtC02CH2, respectively), as well as two other products, the l,3a,6,6a-tetrahydrocyclopenta[ ]pyr-role 1049 (10% and 8% for R = Me and R = EtC02CH2, respectively) and the 7-azabicyclo[4.2.0]octa-2,4-diene 1050 (27% and 12% for R = Me and R = EtC02CH2, respectively) <1995TL7205>. 

A series of enantiomerically enriched tropanes 1057 was synthesized by the rhodium(ll) octanoate-catalyzed reaction of various N-BOC-protected pyrroles 1055 with vinyldiazomethanes 1056 (Equation 249) <1997JOC1095>. 

Slow addition of the vinyldiazomethanes 1059 to a stirred solution of rhodium(ll) octanoate and 2-substituted iV-BOC-pyrroles 1058 in refluxing hexane resulted in the formation of the tropanes 1060 in 53-70% de (30-82% yield) (Equation 250) <1997JOC1095>. Unlike the results seen with the prolinate catalysts (Equations 246 and 247), no [3.3.0]- or [4.2.0]-bicyclic products are formed in these reactions in most cases. Furthermore, the tropane regioselectivity is greater than 10 1 favoring the products derived from initial cyclopropanation at the unsubstituted double bond of the pyrrole. 

The dramatic influence of the 1-siloxy group to enhance tropane formation was observed in the reaction of the compound having the vinyldiazomethane tethered to the 3-position of pyrrole. Rhodium(ii) octanoate-catalyzed decomposition of pyrrole 1066 resulted in the formation of the tropane 1067 that was isolated in 53% yield (Equation 252) <1996JOC2305>. 

The carbene generated by copper-catalyzed decomposition of diazoketone 283 adds intramolecularly to the aromatic carbon-carbon bond of the phenoxy group, affording a norcaradiene derivative that then ring-opens to produce a cycloheptatriene framework fused to the y-lactone in 284 (86T4319). Rhodium(II) octanoate-catalyzed decomposition of 3,4-... 

Rhodium(II) octanoate-catalyzed decomposition of diazo esters 52, involving in the first stage a reaction of a carbenoid with the pyrrole double bond, furnishes polycyclic lactones 53 (34-79% R = H, Me R = H, Ph) (94TL5209) as shown in Scheme 18. 

Wolff rearrangement. Silyl ketenes are readily formed from a-silyl-a-diazoketones on exposure to rhodium(II) octanoate. ... 

Ducept and Marsden described a general synthesis of 5-ethoxy-2-substituted 4-(triethylsilyl)oxazoles 176 from the rhodium(II)octanoate-catalyzed diazo-transfer reaction of ethyl (triethylsilyl)diazoacetate 175 and nitriles (Scheme 1.48). The reaction conditions tolerate a wide variety of functional groups on the nitrile, including alkyl, aryl, heteroaryl, vinyl, carbonyl, sUyloxy, and dialkylamino. Desilylation of 176 with TBAF afforded the corresponding 2-alkyl(aryl)-5-ethoxy-oxazoles 177, which are normally inaccessible from diazoesters using conventional rhodium-carbene methodology. The authors noted that carbonyl groups in the 2 position of 176 are not compatible with TBAF deprotection. 

Asymmetric cyclopropanation. Asymmetric cyclopropanation of styrene can be effected with chiral vinyl or-diazo esters with Rh2(OAc)4 or rhodium(ll) octanoate as catalyst. The products can be converted into optically active cyclopropylamino acids. Of several chiral auxiliaries, (R)-(—)-pantolactone is the reagent of choice. 

Tricyclic dihydropyrrolizinesj The reaction of N-acyl-2-(l-diazoacetyl)-pyrro-lidines (1) with a catalytic amount of a rhodium(II) carboxylate, particularly rhodium(Il) octanoate and a dipolarophile (DMAD), results in a tricyclic dihydropyrrolizine 3 as the major product. The expected product (2) is formed only in traces (10%). Apparently the intermediate carbonyl ylide a rearranges to the more stable azomethine ylide b. 

The synthetic utility of the [3+4] annulation was demonstrated in a short stereoselective synthesis of ( )-tremulenolide A (30, Scheme 11). Rhodium(II) octanoate catalyzed decomposition of the cy-clopentenyldiazoacetate 27 in the presence of the E,Z diene 28 results... 

The intramolecular version of the reaction of vinylcarbenoids with a benzene ring is interesting because several isomeric structures can be formed, and the isolated product is very dependent on the reaction conditions. Rhodium(II) octanoate catalyzed decomposition of 118 at 0 °C, results in forming the norcaradiene 119 in 48% yield (Scheme... 

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