Dieckman cyclizations

A route for the asymmetric synthesis of benzo[3]quinolizidine derivative 273 was planned, having as the key step a Dieckman cyclization of a tetrahydroisoquinoline bis-methyl ester derivative 272, prepared from (.S )-phcnylalaninc in a multistep sequence. This cyclization was achieved by treatment of 272 with lithium diisopropylamide (LDA) as a base, and was followed by hydrolysis and decarboxylation to 273 (Scheme 58). Racemization could not be completely suppressed, even though many different reaction conditions were explored <1999JPI3623>. 

Cyclooctanone has been prepared by distilling the calcium and thorium salts of azelaic acid, by heating azelaic acid with barium oxide in the presence of iron, by the action of nitrous acid on l-(aminomethyl)-cycloheptanol, by Dieckman cyclization of azelaic acid dimethyl ester and diethyl ester, and by ring expansion of cycloheptanone with diazomethane. ... 

Michael adducts between the hydrazines and dimethyl acetylenedicarboxylate (DMAD), and Dieckman cyclization of l,l -bipyrroletetraacetic ester have been used in the synthesis of 1,2-diazepines <1996CHEC-II(9)113>. 

A mechanism consisting of consecutive Dieckman cyclizations, possibly through an anhydride intermediate even in the polyacid case appears in accord with the observations. 

Cycloadditions. The anion of the methyl cyclopcntanccarboxylate I when treated with methyl acrylate undergoes sequential Michael-Michael-Dieckman cyclization to form the spirobicyclic cyclohexanone /3-keto ester 2 as a mixture of two diastcrcomcrs (41% yield). Decarboxylation of 2 followed by addition of CH,MgBr... 

The strategy was based on a Huisgen pyrrole synthesis to build the B and C rings followed by a Dieckman cyclization to form ring A. The acetoxy acid (428) available in two steps from 4-hydroxy-... 

Two routes to the pentacyclic yohimbine skeleton carrying ester groups at C-16 have been described. Dieckman cyclization " (Scheme 8) of (37), a synthetic precursor of (38), leads to a major product in which closure occurs in the desired sense, in contrast to a comparable reaction on (38). 

In a related process, Dieckman cyclization of the l,r-bipyrroletetraacetic ester (138) affords [10A,10c]diazapyracehetylene derivatives (139) and (140) (Scheme 19) <85TL5425,85TL5429). 

Reactions involving other alkali metals are not as numerous. The properties of colloidal alkali metals have been known for many years but they remain unexploited in synthesis due to the difficulties associated with their preparation. Luche and co-workers observed that small lumps of potassium could be dispersed in a few minutes by sonication in toluene or xylene at 10 °C in a cleaning bath [83], The colloid generated was used in a number of reactions for instance, a Dieckman cyclization could be effected within 5 min (Scheme 40). 

Stork and Raucher described the first synthesis of a natural prostaglandin (PGA2) (66) from the simple sugar erythrose (60) which is distinguished because it avoids totally the need for separation of enantiomers. The route, outlined in Scheme 19, includes two Claisen rearrangements, one to produce the is-geometry of the (13,14-) double bond (61) -> (62), the other to transfer chirality of the C—O bond to that of a non-adjacent C—C bond, viz. (63) (64), and uses the Dieckman>, cyclization... 

A few reduced systems have been prepared by conventional condensations. A Dieckman cycli-zation gave pyrrolopyrazinone (224) (Equation (84)) <92JCS(P1)1035>, a similar condensation the pyrrolothiazinone (225) (Equation (85)) <9lEUP4l52ll>, and treatment of the dibromide (226) with sulfinate caused cyclization to pyrrolopyrimidinones (227) (Equation (86)) <88CPB3887>. 

In subsequent studies, Szantay s group further improved their syntheses of yohimbine (4) and j5-yohimbine (5). In addition, the ketone 260 was resolved, thus effecting a chiral synthesis of these alkaloids (Scheme 3.43) (55). The levorotatory enantiomer of ketone 260 was converted to the a, -unsaturated ester (-h)-261 which was then cyclized by the Dieckman method to afford (—)-271. Treatment of this unsaturated ketone with sodium borohydride in the presence of nickel chloride afforded a 2 1 mixture of (—)-j -yohimbine (( —)-5) and ( + )-yohimbine ((-h)-4). Furthermore, the ( + )-ketone ((-h)-260) was carried through the aforementioned sequence to yield a mixture of (-l-)-j8-yohimbine ((-h)-5) and ( —)-yohimbine ((—)-4). 

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