Cyclopentanols synthesis

The Brook 1,4-rearrangement is useful in cyclopentanol synthesis. For example, Schaumann and co-workers demonstrated that lithiated or-silyl dithiane 112 was useful for construction of cyclopentanol 115. Addition to epoxytosylate 113 followed by 1,4-silyl migration provided lithiodithiane 114 for closure of the five-membered ring. ... 

Another example of a [2s+2sh-1c+1co] cycloaddition reaction was observed by Barluenga et al. in the sequential coupling reaction of a Fischer carbene complex, a ketone enolate and allylmagnesium bromide [120]. This reaction produces cyclopentanol derivatives in a [2S+2SH-1C] cycloaddition process when -substituted lithium enolates are used (see Sect. 3.1). However, the analogous reaction with /J-unsubstituted lithium enolates leads to the diastereoselective synthesis of 1,3,3,5-tetrasubstituted cyclohexane- 1,4-diols. The ring skeleton of these compounds combines the carbene ligand, the enolate framework, two carbons of the allyl unit and a carbonyl ligand. Overall, the process can be considered as a for-... 

The synthesis of the cyclopentanol 8 was racemic and required chiral resolution. 

Krische and coworkers [44] developed a Rh-catalyzed asymmetric domino Michael/aldol reaction for the synthesis of substituted cyclopentanols and cyclohex-anols. In this process, three contiguous stereogenic centers, including a quaternary center, are formed with excellent diastereo- and enantioselectivity. Thus, using an enantiopure Rh-BINAP catalyst system and phenyl boronic acid, substrates 2-108 are converted into the correspondding cyclized products 2-109 in 69-88% yield and with 94 and 95% ee, respectively (Scheme 2.24). 

If no y-H atom is available, or if for sterie reasons abstraction of a 6-H atom is facilitated, this latter reaction occurs with formation of a cyclopentanol. A series of such sequences has been used in the synthesis of dodecahedrane 409a,b>. 

This protocol is also effective for the cyclization of an allenylaldehyde, the synthetic utility of which has been demonstrated in the synthesis of (+)-testudinariol A (Scheme 16.89) [97]. Cyclization of an allenylaldehyde provides a ris-cyclopentanol bearing a 2-propenyl group at the C2 position. The reaction mechanism may be accounted for by coordination of Ni(0) with both the aldehyde and the proximal alle-nyl double bond in an eclipsed fashion with a pseudo-equatorial orientation of the side chain, oxidative cyclization to a metallacycle, followed by Me2Zn transmetalla-tion and reductive elimination. 

Substrates include benzyl (2 g) and cinnamyl (2.7 g) alcohols to acids cyclopentanol (1 g), benzhydrol (3.9 g), benzoin (4 g), pantolactone (2.6 g) to ketones (RuCy TCCA/( Bu N)Br/aq. Kj(C03)/CH3CN) (Fig. 2.14) [25] [[2-[2-hydroxypropyl) amino]-l,2-dioxoethyl]amino]acetic acid ethyl ester (6.21 kg) to [(l,2-dioxo-2-oxopropyl)amino]ethyl)amino] acetic acid ethyl ester, part of the industrial-scale synthesis of thrombin inhibitor (RuCyaq. Na(BrOj)/CH3CN) [166] (H-)-dihydroc-holesterol (8 g) to cholest-3-one (RuO /aq. K(10 )/(BTEAC)/CHCl3) [308] ... 

We already know from part (a) how to convert / runs-2-methy I c yc I ope n tanol to ris-2-methyl-cyclopentyl acetate. So all that is really necessary is to design a synthesis of frans-2-methyl-cyclopentanol. Therefore,... 

Christoph, G. Hoppe, D. Asymmetric synthesis of 2-alkenyl-l-cyclopentanols via Sn-Li exchange and intramolecular cycloalkylation. 

Tetronates derived from l,3-divinyl-2-cyclopentanol were employed to study the possibility of a differentiation of enantiotopic or diastereotopic double bonds in their [2 + 2]-photocydoaddition [140]. It was found that tetronate 148 underwent a selective [2 + 2]-photocydoaddition (r.r. = 75/25) at one of the two possible double bonds to deliver product 149 in 67% yield (Scheme 6.52). The reaction was analyzed regarding the preferred conformations of the cyclopentanol, with the notion that the tetronate resides in a pseudoequatorial position, and the vinyl group in a pseudoaxial position of the envelope conformation. Intermediate 149 served as starting material for the first total synthesis of the tetracydic sesquiterpene (T)-punctaporonin C (150) [141]. 

The generation of ketyl radicals and their intramolecular addition to tethered olefin to obtain cyclopentanol derivatives have also been achieved by Pandey et al. [102] by using such as those shown in Figures 8.2. An interesting application of this strategy is demonstrated by the synthesis of C-furanosides 231 (Scheme 8.64). 

Belotti, D., Cossy, J., Pete, J.P., and Portella, C. (1986) Synthesis of bicyclic cyclopentanols by photoreductive cyclization of 8,e-unsaturated ketones. Journal of Organic Chemistry, 51, 4196-4200. 

The synthesis of bicyclic cyclopentanols (46) via photoreductive cyclization of 5,8-unsaturated ketones (45) has been realized by Belotti et al. using hexamethylphosporic triamide (HMPA) or triethylamine (TEA) as electron donor [46]. The photocyclization proceeded remarkably efficient when HMPA was used as donor and solvent (Sch. 24). Furthermore, only one stereoisomer was obtained carrying methyl and hydroxy groups in trans-configuration. In contrast, the yields for cyclization dropped significantly when TEA in a polar solvent such as acetonitrile was used. As an example, the yield for 46 (n= 1) decreased from 81% in HMPA to 50% in TEA/ MeCN. 

The norephedrine-derived Masamune asymmetric aldol reaction was utilized in the total synthesis of (+)-testudinariol A (12), a triterpene marine natural product that possesses a highly functionalized cyclopentanol framework with four contiguous stereocenters appended to a central 3-alkylidene tetrahydropyran6 (Scheme 2.2f). The norephedrine-derived ester 13 was enolized with dicyclo-hexylboron triflate and triethylamine in dichloromethane and then treated with 3-benzyloxypropanal to afford the aldol adduct (14) as a 97 3 mixture of anti/syn diastereomers in 72% yield. Diastereoselectivity within the anti -manifold was 90 10. Protection of alcohol as the methoxyethoxymethyl (MEM) ether followed by conversion of the ester to an aldehyde by LiAlELt reduction and subsequent Swem oxidation gave the aldehyde 16 in 64% yield over three steps. 

In DMF containing lithium perchlorate, reduction of o -bromopropiophenone at mercury gives l,4-diphenyl-2,3-dimethylbutan-l,4-dione in 65% yield [236]. However, electrolysis of a-bromopropiophenone in the presence of benzoyl chloride affords only l,3-diphenyl-2-methylpropan-l,3-dione. Other studies involving reduction of phenacyl bromides include the electrosynthesis of 4-aryl-2-methylfurans [237] and the regioselective synthesis of enol carbonates [238] semicarbazones of phenacyl bromide can be converted into 3,7-diaryl-2/7-imidazo[2,l-Z>][l,3,4]oxadiazines [239]. Reduction of 1,2-dibenzoyl-chloroethane at mercury in DMF containing lithium perchlorate affords mixtures of phenyl tribenzoyl cyclopentanols and diphenyl dibenzoyl butanediones [240]. 

The Barbier reaction has been used for the synthesis of alcohols that were difficult to prepare by normal Grignard reagent techniques. This is particularly true for the preparation of cyclic alcohols from halogenated ketones. Several researchers [49-51] have shown that cyclobutanols and cyclopentanols can be prepared in good yields from <5- and y-iodo- and bromoketones in either solvents with Mg or Mg/HgCl2 [Eq. (17)]. 

Cp2Ti(CO)2 reacts with with 2 equiv. of cr,/ -unsaturated ketones to yield the nine-membered titana-2,9-dioxacy-clonona-3,7-dienes, which can be used for the selective synthesis of substituted cyclopentanols, diketones, or cyclopentenes. X-ray crystal structures and ab initio calculations have been reported.1544... 

Cyclopentyl chloroformate, C5H9OCOCI. Mol. wt. 148.59, b.p. 69-70,5°/25 mm. The reagent is prepared by the reaction of cyclopentanol with phosgene and has found some use in peptide synthesis for introducing the carbocyclopentyloxy group as... 

Starting with optically active c -2-[A -cyanomethyl-A -(15-phenethyl]-l-[(3,4-methylenedioxy)phenylethynyl]cyclopentanol (365), 3-[(3,4-methy-lenedioxy)phenyl] -N- [(lS-phenethyl[hexahydroindolin-4-one (366) was synthesized in a manner similar to that noted previously. Thus, the synthesis of (-)-pancracine (339) was achieved in 25% overall yield through 366 by a sequence of reactions similar to those noted for ( )-339 (180b) (Scheme 39). Also, the same intermediate 364 employed for the synthesis of ( )-339 was transformed to ( )-desmethyl-a-isocrinamine (3 ) by way of the 3a-acetoxy derivative 367. 

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