Ring construction synthesis

Martin JD, Perez C, Ravelo JL. Enantioselective ring construction synthesis of halogenated marine natural spiro[5.5] undecane sesquiterpenes. J. Am. Chem. Soc. 1986 108(24) 7801-7811. 

Remarkably few examples of this type of ring construction are available. The cobalt carbonyl hydride catalyzed hydroformylation of A/,A/ -diallylcarbamates has provided 3-pyrrolidinones (Scheme 61a) (81JOC4433). The pyrrole synthesis shown in Scheme 61b depends on Michael addition of ethyl a-lithioisocyanoacetate to ethyl a-isocyanocrotonate (77LA1174). 

The Balz-Schiemann reaction continues to attract attention, with much of it generated by the interest in fluoroquinolones, e.g., (7), which is a potential antibacterial. Two approaches to its synthesis are possible—introduction of fluorine prior to or post ring construction. Decomposition of the tetrafluoroborate salt was unsuccessful, whereas the PF6 salt (8) gave only a poor yield (84JMC292). A more successful approach was the introduction of F into the pyridine nucleus prior to formation of the 1,8-naphthyridine ring (84JHC673). A comparison of decomposition media showed that cyclohexane was the best with regard to yield and time. 

In contrast to the Johnson s D —> A-ring construction approach, Brown devised an A —> D-ring construction approach [22]. Starting from Wieland-Miescher ketone (30), a common source of the A, B-rings in the de novo synthesis of steroids, the C-ring was introduced via hydrazone allylation, ozonolysis, aldol condensation, and olefin isomerization (31 > 32). The D-ring was assembled by a reductive alkylation... 

At this point, we had exerted an immense amount of effort to overcome a number of difficult transformations and their unprecedented challenges (1) oxidation at C3 and C3a, (2) reduction at C8a, and (3) homologation at C5a. We learned to truly respect the unique structural topology that ABD-tricycle 2 possesses. What remained for the total synthesis was the C-ring construction, which posed serious challenge of its own. 

If ammonium thiocyanate is used, the ammonium ion can itself provide a nitrogen atom for heterocyclic ring construction. Such nitrogen and sulfur transfer is the basis of an elegant synthesis of isothiazoles (15) from 3-chloropropenals (16).18... 

Resin bound dipeptides have been used in the parallel synthesis of 3,4,7-trisubstituted 4,5,8,9-tetrahydro-3//-imidazo l, 2-a l, 3,5 triazcpinc-2(7//)-thioncs and Af-alkyl-4,5,7,8-tetrahydro-3//-imidazo[ 1,2-a][l, 3,5]triazepin-2-amines by ring construction methodology <06JCOl27>. 

This chapter deals with [2 + 2]cycloadditions of various chromophors to an olefinic double bond with formation of a four-membered ring, with reactions proceeding as well in an intermolecular as in an intramolecular pattern. Due to the variety of the starting materials available (ketones, enones, olefins, imines, thioketones, etc.. . .), due to the diversity of products obtained, and last but not least, due to the fact that cyclobutanes and oxetanes are not accessible by such a simple one-step transformation in a non-photo-chemical reaction, the [2+2]photocycloaddition has become equivalent to the (thermal) Diels-Alder reaction in importance as for ring construction in organic synthesis. 

The metal-catalyzed [5 + 2]-cycloaddition reaction of VCPs and 7t-systems provides a new concept for seven-membered ring construction that has been significantly advanced over the last decade in the areas of catalyst development, chemo-, diastereo-, and enantioselectivity, substrate scope, and applications to total synthesis. 

Move 3] This work surveys complementary routes for the synthesis of pyrazolo[f,5-a] pyrimidine-7-ones 1 and pyrazolo[l,5-a]pyrimidin-5-ones 2. The use of 1,3-dimeth-yluracil 3 as an electrophile for pyrimidine ring construction affords pyrazolo[f,5-a] pyrimidin-5-ones 2, contrary to literature reports. Novel use of trans-3-ethoxyacrylate 4 as an electrophile also afforded 2, and the isolated intermediates from this reaction support our proposed mechanism. (55 words)... 

Due to the plethora of bicyclo[5.3.0]ring systems in natural products and the limited number of efficient methods that facilitate the construction of seven-membered rings the synthesis of bicyclo[5.3.0]compounds based on a PK reaction has recently been a subject of intense interest. Generally, the preparation of larger ring systems [n.3.0] (n>4) has proven challenging with traditional PK reaction catalysts. One of the few examples reported is the Co2(CO)g catalyzed formation of the azabicyclo[5.3.0j-decenonone derivative 15 (X = OTBS) from the conformationally restricted substrate 14... 

Two major types of transformations are usually used for the synthesis of benzazepines with the fused pyrrole and indole rings. Construction of the... 

Stoodley developed an asymmetric synthesis of (5A)-2,3,4,5-tetrahydropyridazine-3-carboxylic acid (see Section 8.01.6.4). The ring construction was achieved via cycloaddition of dienes 295 bearing a tetraacetyl /3-D-glucopyranosyl moiety for chiral induction with azodicarboxylates (Equation 73) <1999J(P1)2591>. 

Deacetoxyalcyonin acetate 1 and cuncellin 2 are representative members of the euniccllin class of diterpenes. The synthesis of deacetoxyalcyonin acetate 2 by Gary Molander of the University of Pennsylvania (J. Am. Chem. Soc. 2004, /26,1642) illustrates the power of intramolecular organometallic carbonyl addition for ring construction. 

From aryl halide 110 From alcohol 156 Protection 100, 101, 144 Amino acid from hydroxy acid 40 Amphidinolide synthesis 50,94 Anatoxin synthesis 82 Aromatic ring construction 171,191 Aromatic ring substitution 10,18,19,21, 48, 54, 65,69, 104, 108, 110, 111, 120, 122,138, 149, 164, 171, 174, 175, 190,205... 

A dominant feature of the type c ring-construction approach to azepine systems has been ruthenium-catalyzed ringclosing metathesis reactions. Examples include the synthesis of the azepine derivative 157 from 156 using either the Grubbs type I catalyst 159 or type II 160. The diene precursor 156 was prepared in turn from 154 via 155, as shown in Scheme 21. Hydrogenation of the C-C double bond in 157 afforded the azepane 158 <2005SL631>. 

An asymmetric synthesis of 3,4,5-trisubstituted-tetrahydro-l-benzazepines has been reported based on a type a ring construction process mediated by triethylaluminium with a chiral amino ester followed by lactam reduction with borane <2006OL2667>. Dynamic thermodynamic resolution in a lithiation-substitution sequence was integral to the preparation of the amino ester. An acid-catalyzed ring construction approach to the asymmetric synthesis of 4,5,6-trisubstituted- and 3,4,5,6-tetrasubstituted azepanes based on chiral acyclic precursors has also been described <2006JA2178>. 

Further application of the powerful intramolecular reductive Heck reaction has been realized in the efficient microwave-assisted synthesis (Pd(PPh3)4, 3 mol%, HCOONa, 1.5 equiv, DMF HzO 3 1, 110 °G) of the important 3-benzazepine system. The precursors were A-ethynoyl derivatives of N-substituted n-bromophenethylamines, which afforded, via a type c ring construction, 3-benzazepin-2-ones with a substituted exocyclic methylene group at the Cl position <20070L3017>. 

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