Aldehydes intramolecular cyclization

Thus, simple ketones or aliphatic aldehydes may be successfully used as starting materials in the CSIC (Carbanion mediated Sulfonate Intramolecular Cyclization) reaction. Ai-alkylsulfonamides could be also cyclized under CSIC conditions (99T(55)7625) affording the spiroisothiazoline 79. By treatment with TMSCl, Nal in acetonitrile at r.t., hydrolysis of the enamine and formation of the corresponding keto derivative 80 was obtained. 

Aziridinium ion-based click chemistry provides convenient access to pyrazolo[l,2-ajpyrazoles, active inhibitors of penicillin-binding proteins [58, 59]. Ring-opening of aziridinium ions 32 at the benzylic position with hydrazine, followed by intramolecular cyclization, gave pyrazolidin-3-ones 37 in excellent yields (Scheme 12.27). Heating of the hydrazides 37 with aromatic aldehydes at reflux in absolute... 

The intramolecular cyclization of diketo-enals and keto-enals was accomplished by the combination of a cationic Rh complex and fn(2-furyl)phos-phine (2 - Fur3P). The corresponding bicyclic hydroxy-aldehydes were produced in good to excellent yields, as demonstrated by the formation of 74,76 and 78 (Scheme 22) [36]. 

It is well known that in the cyclization of a y-hydroxy aldehyde to form the corresponding six-membered ring hemiacetal through intramolecular cyclization the hemiacetal form always predominates (48). This might account for the fact that no noticeable carbonyl absorption has been observed in the IR and NMR spectra of 54. However, the equilibrium between the hemiacetal and the aldehyde forms might shift in favor of the aldehyde form as the borane reduction proceeds until 54 is completely transformed to 55. 

There are two important rhodium-catalyzed transformations that are broadly used in domino processes as the primary step. The first route is the formation of keto carbenoids by treatment of diazo keto compounds with Rh11 salts. This is then followed by the generation of a 1,3-dipole by an intramolecular cyclization of the keto carbenoid onto an oxygen atom of a neighboring keto group and an inter- or intramolecular 1,3-dipolar cycloaddition. A noteworthy point here is that the insertion can also take place onto carbonyl groups of aldehydes, esters, and amides. Moreover, cycloadditions of Rh-carbenes and ring chain isomerizations will also be discussed in this section. 

An intramolecular azomethine ylide-mediated cyclization has been used to access the core 5 6 5 angular tricyclic structure of martinellic acid by Snider (Equation 113) <20010L4217>. Reaction of IV-benzylglycine 420 with the aldehyde 419 led to intramolecular cyclization, giving 421 in good yield. 

Differently substituted pyrrolopyrroles can be constructed from a 1,3-dipolar cycloaddition, between the adduct from glycines and aldehydes and maleimides. Then, for example, the initially formed iV-allyl-o-bromophenyl-substituted pyrrolopyrrole mixture, 223, + 224, can then undergo an intramolecular cyclization in the presence of catalytic palladium(O) to give the pyrroloindolizine 225 <1991TL1359> (Scheme 61). 

A series of new pyrazoloindolizinium salts has been prepared for their interest as dyestuffs. The amide 278 undergoes an intramolecular cyclization to the tricycle 279 upon heating in an ethanol/piperidine mixture. The methylene group of this can then react with different electrophiles, for example, aldehydes, to extend the chromo-phore <2002JCCS571> (Scheme 76). 

As can be seen in the scheme below, insertion reactions of aldehydes to the C-H bond of aromatic ketimines by using a rhenium catalyst provided benzo[c]furans via a mechanism involving consecutive steps of C-H bond activation, insertion of aldehyde, intramolecular nucleophilic cyclization, reductive elimination, and elimination of aniline <06JA12376>. 

The intramolecular cyclization of l,2-dien-7-ynes and l,2-dien-6-ynes regiospecifically affords the corresponding titanacycles, which react with protons, carbon monoxide, aldehydes, or imines to give single products, as shown in Eqs. 9.56 and 9.57 [102], As the formation of titanacycles and their subsequent reaction with externally added reagents such as carbon monoxide (Eq. 9.56) or an aldehyde (or imine) (Eq. 9.57) proceeds with excellent chirality transfer, this represents a new method for synthesizing optically active cyclopentane derivatives from optically active allenes [102]. 

Several characterized NRPSs utilize alternative methods for chain termination. In some synthetases, the TE domain of the final module is replaced by an NAD(P)H-dependent reductase domain. Reduction of a peptidyl-S-PCP substrate through a two-electron reaction leads to the formation of a transient aldehyde, which is subsequently converted into a cyclic imine or hemiaminal through intramolecular cyclization. This two-electron reaction is utilized in the biosynthesis of nostocyclopeptides, the saframycins, ° and anthramycin. Alternatively, a four-electron reduction to the primary alcohol is observed in the biosynthesis of mycobacterial peptidolipids, linear gramicidin," " the myxalamides, lyngbyatoxin, " and myxochelin A 75,76 alternative four-electron reduction pathway involving aldehyde formation, transamination, and reduction to a primary amine occurs in the biosynthesis of myxochelin B. ... 

Several 2-thiazolyl- (194) and 2-benzothiazolyl- (197) hydrazones of aromatic aldehydes undergo oxidative intramolecular cyclization to form 1,2,4-triazolo-bridgehead heterocycles 195 (95SC3363) (Scheme 53) and 198 [93JCR(S)244] (Scheme 54), respectively. In the case of 194, l-acetoxy,l-(4-aryl-2-thiazolyl)-2-aroylhydrazines (196) are formed as minor products (Scheme 53). 

Oxandrolone Oxandrolone, 17j3-hydroxy-17a-methyl-2-oxa-5-androstan-3-one (29.3.10), is made by oxidation of the C1-C2 double bond of 17j3-hydroxy-17a-methyl-l-androsten-3-one by a mixture of lead tetraacetate and osmium tetroxide with an opening of the A ring of the steroid system, which forms an aldehyde acid (29.3.9). Upon reducing the aldehyde group with sodium borohydride, intramolecular cyclization takes place, directly forming a lactone (29.3.10), which is the desired oxandrolone [31,32]. 

Ganter has developed three different approaches to tricyclo[5.2.1.0 ]decane (403), yet another of the nineteen isomeric hydrocarbons of adamantaneland As seen in Scheme XXXIII, the routes involve intramolecular cyclization of keto tosylate 399 followed by Wolff-Kishner reduction of the resulting ketone, thermo-cyclization of 400 and subsequent dechlorination, hydrogenation, and photocycli-zation of aldehydes 401. Majerski s approach involved hypoiodite cleavage of alcohol 402... 

In a similar manner, intramolecular cyclization of the O-stannyl ketyl derivatives 201 and 206, generated from the oxazolyl aldehydes 200 and 205, provides a facile method for the chiral synthesis of 3-hydroxy-2-(hydroxymethyl)-5-substimted-pyrrolidines 202 and 203 and the piperidine analogues 207 and 208 that can be successfully transformed into naturally occurring amino alcohols, (+)-bulgecinine 204 and (—)-desoxoprosopinine 209, respectively (Fig. 

Radical cyclizations are often used in ring formations and are an effective methodology in the synthesis of piperidines. The intramolecular cyclization of an oxime ether, such as 63 onto an aldehyde or ketone gives a new entry into cyclic amino alcohols <99JOC2003, 99H(51)2711>. Similarly, reaction of a terminal acetylene with BujSnH generates a vinyl radical, which will cyclize with an imine moiety to give 3-methylenepiperidine <99TL1515>. The indolizidine alkaloid ipalbidine was prepared by a sulfur-controlled 6-exo-selective radical cyclization of an a/p/ia-phenylthio amide <99H(50)31>. 

Furo[2,3- ]pyridines are generated in a cyano [4-1-2] reaction that uses tungsten alkynols and aldehydes which cyclize to 1,3-dienes prior to reaction with nitriles (Scheme 9) <1998JA4520>. The reaction, which is activated by photolysis or with Me3N0-H20, works with unactivated nitriles in both intramolecular and intermolecular reactions to give moderate to good yields of product. 

Aldehyde groups in C-formylazoles can participates in intramolecular cyclizations. Thus, reduction of l-(2-nitrophenyl)-imidazole-2-carbaldehyde (557) with sodium dithionite leads via amine (558) to imidazo[l,2-fl]quinoxaline (519) with good yield (71KGS570). 

BSB451). Metalated enamines (in the a-methyl group) easily react with aldehydes, and the new enamines thus formed undergo an intramolecular cyclization giving 2-pyrone derivatives (84T733) (Scheme 41). 

Alkyl-hexahydro-l,3,5-triazin-2-ones are prepared by the reaction between urea, formaldehyde and primary amines (73S243). The intermediate polycondensate (87) undergoes intramolecular cyclization on heating to yield the desired product (Scheme 52). By using substituted ureas (or thioureas) and/or different aldehydes, a wide variety of N-substituted 5-alkyl-hexahydro-l,3,5-triazin-2-ones (or 2-thiones) may be prepared. 

Intramolecular cyclization of keto aldehydes. The first synthesis of the sesquiterpene bicyclogermacrene (2) has been achieved by cyclization of 1 with TiCl3-Zn/Cu to give 2 and the isomer 3. 

Azomethine imine cycloadditions provide access to pyrazolidines, pyrazolines and pyrazoles. Intramolecular cyclizations were first reported in 1970.78 The main method for generation of azomethine im-ines involves reaction of a 1,2-disubstituted hydrazine with an aldehyde or an aldehyde precursor. 

In the course of the total synthesis of enmein, Fujita and co-workers (7) have discovered that the intramolecular cyclization of the enolate 23 of the corresponding tetracyclic keto-aldehyde at room temperature gave only ketol 24. However, when the same reaction is conducted at 60°C, thermodynamically controlled conditions prevail, and the epimeric product 25 is obtained. Inspection of molecular models indicates that the kinetically controlled product 24 is again the result of an anti peri planar arrangement of the enolate and the aldehyde double-bonds. Also, as in the previous examples, the isomer 25 comes from a synclinal arrangement of the reacting functional groups. 

The highly stereoselective synthesis of 2,3-fr,ms--3-hydroxytetrahydropyran and 2,3-/ra r-3-hydroxyoxepane was achieved by the Sml2-induced reductive intramolecular cyclization from acyclic compounds having an aldehyde and a /3-alkoxyacrylate fragments <2002CL148>. Based on this reaction, new effective iterative syntheses of trans-fused 6,6,6-tricyclic, 6,7,6-tricyclic, and 6,7,7,6-tetracyclic ethers were developed <2002T1853>. 

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