Annulation cascade

Thus, Nilsson reported an interesting approach for the assembly of tetracyclic benzofuran derivatives via the Cu( I)-mediated cydization-annulation cascade reaction of o-alkynylphenol 1 and o-iodophenol 3 (Scheme 9.1). The formation of benzofuran 4 was rationalized by the proposed involvement of a nucleophilic benzofuranylcopper intermediate 2. The latter, upon coupling and subsequent lactonization with 3, furnished the corresponding polycyclic product 4 [78]. 

Scheme 37 Brpnsted acid-catalyzed redox-neutral indole annulation cascades...

Ruan, J., Iggo, J. A., Xiao, J. (2010). Direct synthesis of 1-Indanones via Pd-catalyzed olefination and ethylene glycol-promoted aldol-type annulation cascade. Organic Letters, 13,268-271. 

In a very nice titanium-mediated annulation cascade, Cheng and Micalizio [80] synthesized functionalized, bicychc [3] dendralenes 133 in situ as intermediates that were trapped via a subsequent DA reaction (Scheme 1.18). The report includes one example of a DA dimerization product, seven examples of intermolecular metallocycle-mediated annulation followed by intermolecular [4-1-2] cycloaddition reaction to afford (135), and one example of an isolated, acyclic substituted [3]dendralene 137. 

Zhang ZW, Li WDZ. A facile total synthesis of hainanensine via an unusual rearrangement-annulation cascade. Org. Lett. 2010 12(8) 1649 1651. 

In an alternative approach to annulation across the indole 2,3-tt system, Padwa and coworkers have reported approaches to the pentacyclic and hexacyclic frameworks of the aspidosperma and kopsifoline alkaloids respectively that involve as the key step a Rh(II)-promoted cyclization-cycloaddition cascade <06OL3275, 06OL5141>. As illustrated in their approach to ( )-aspidophytine 150, Rh2(OAc)4-catalyzed cyclization of a diazo ketoester 148 affords a carbonyl ylide dipole that undergoes [3+2]-cycloaddition across the indole 2,3-tt bond to generate 149 <06OL3275>. 

The radical carboazidation of alkenes has been achieved in water using triethylborane as initiator [118]. This efficient process is complete in one hour at room temperature in an open to air reaction vessel (Scheme 54, Eq. 54a). These new tin-free carboazidation conditions are environmentally friendly and allow to run reactions with an excess of either the alkene or the radical precursor. They are also suitable for simple radical azidation of alkyl iodides as well as for more complex cascade reactions involving annulation processes (Eq. 54b). In both reactions (Eq. 54a and 54b), an excess of triethylborane (3 equivalents) is required to obtain a good yield. This may be an indication that the chain process, more precisely the reaction between the phenylsul-fonyl radical and Et3B, is not efficient. 

Intramolecular Allylboration. In one rare but impressive example involving a masked aldehyde, a domino hydroformylation/allylboration/hydroformyla-tion reaction cascade has been designed to generate bicyclic annulated... 

The number of similar cyclizations, including tandem and cascade sequences where an SnH reaction is a key step, has been considerably increased. As a rule, they are easily performed allowing at times the synthesis of complex polynuclear heterocycles in one step. The present paper, which summarizes about 130 articles on this topic, shows SnH cyclizations to be a very promising strategy for heterocyclic ring annulations. 

On the basis of preceding experience in the synthesis of methylenecyclopentanes, Curran discovered a cascade reaction proceeding via a 4 + 1 radical annulation mechanism that led to a new synthesis of cyclopenta-fused quinolines [60] (Scheme 16.15). 

A highly efficient cascade reaction of propargyl 2-bromoallyl ethers with a tethered 3-oxoalkyne has been described to give efficient access to tricyclic [c]-annulated furans <2007JOC1395>. [f]-Annulated furans have also been made... 

In addition to cationic cyclizations, other conditions for the cyclization of polyenes and of ene-ynes to steroids have been investigated. Oxidative free-radical cyclizations of polyenes produce steroid nuclei with exquisite stereocontrol. For example, treatment of (259) and (260) with Mn(III) and Cu(II) afford the D-homo-5a-androstane-3-ones (261) and (262), respectively, in approximately 30% yield. In this cyclization, seven asymmetric centers are established in one chemical step (226,227). Another intramolecular cyclization reaction of iodo-ene poly-ynes was reported using a carbopaUadation cascade terminated by carbonylation. This carbometalation—carbonylation cascade using CO at 111 kPa (1.1 atm) at 70°C converted an acycHc iodo—tetra-yne (263) to a D-homo-steroid nucleus (264) [162878-44-6] in approximately 80% yield in one chemical step (228). Intramolecular aimulations between two alkynes and a chromium or tungsten carbene complex have been examined for the formation of a variety of different fiised-ring systems. A tandem Diels-Alder—two-alkyne annulation of a triynylcarbene complex demonstrated the feasibiHty of this strategy for the synthesis of steroid nuclei. Complex (265) was prepared in two steps from commercially available materials. Treatment of (265) with Danishefsky s diene in CH CN at room temperature under an atmosphere of carbon monoxide (101.3 kPa = 1 atm), followed by heating the reaction mixture to 110°C, provided (266) in 62% yield (TBS = tert — butyldimethylsilyl). In a second experiment, a sequential Diels-Alder—two-alkyne annulation of triynylcarbene complex (267) afforded a nonaromatic steroid nucleus (269) in approximately 50% overall yield from the acycHc precursors (229). 

Curran s photocatalytically induced radical [4+1] annulation of phenyl isocyanide (13) and bromopyridone (14) represents the key step of the campto-thecin synthesis [80, 81]. The remarkable one-step synthesis of the tetracyclic heterocyclic system starts with photolytic cleavage of hexamethylditin to form the Me Sn radical, which then cleaves the C-Br bond in 14. This new radical reacts with the isonitrile carbon to form 15 which yields the final 16 via two subsequent radical intermediates (eq. (8)) (cascade or domino reaction [65, 66]). 

As depicted below, a procedure for the iodocyclization of acetoxy-containing 2-(l-alkynyl)anisole and subsequent direct palladium-catalyzed earbonylatiori/lactonization was reported as an efficient entry to naturally occurring eoumestan and coumestrol <05IOC9985>. A novel Pd(II)-mediated cascade carbonylative annulation of substituted o-hydroxyphenylacetylenes to give benzo[fo]furan-3-carboxylie adds was achieved in a one-pot reaction <050L2707>. 

Benati L, Calestani G, Leardini R, Minozzi M, Naimi D, Spagnolo P, Strazzari S, Zanardi G (2003) Cascade radical reactions via a-(arylsulfanyl)imidoyl radicals competitive [4-1-2] and [4+1] radical annulations of alkynyl isothiocyanates with aryl radicals. J Org Chem 68 3454-3464... 

Based on enantioselective epoxidation and subsequent ring opening and closing, the so-called Achmatowicz reaction was developed. This is an organocatalytic one-pot cascade for the annulation of a,(J-unsaturated aldehydes, hydrogen peroxide, p-carbonyl compounds and NBS, which furnish optically active 3-pyrones. Other chiral heterocycles were also assembled by organocatalytic cascade reactions using diaiylprolinol silyl ethers as catalysts. ... 

In 2008, the Bode group documented a highly enantioselective cis-cyclopentene-forming annulation of enals and -4-oxo-2-butenoate using a chiral triazolium salt. A cascade sequence involving a catalytic, asymmetric... 

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