Spiro decane synthesis

The general features of the monensin synthesis conducted by Kishi et al. are outlined, in retrosynthetic format, in Scheme 1. It was decided to delay the construction of monensin s spiroketal substructure, the l,6-dioxaspiro[4.5]decane framework, to a very late stage in the synthesis (see Scheme 1). It seemed reasonable to expect that exposure of the keto triol resulting from the hydrogen-olysis of the C-5 benzyl ether in 2 to an acidic medium could, under equilibrating conditions, result in the formation of the spiroketal in 1. This proposition was based on the reasonable assumption that the configuration of the spiroketal carbon (C-9) in monensin corresponds to the thermodynamically most stable form, as is the case for most spiroketal-containing natural products.19 Spiro-ketals found in nature usually adopt conformations in which steric effects are minimized and anomeric effects are maximized. 

Sattelkau and Eilbracht90 have exploited the Claisen rearrangement of allyl vinyl ethers in their synthesis of several spiro compounds. As shown below in equation 62, 7,9-dimethyl-l,4-dioxa-spiro[4,5]decan-8-one, 118, was converted to a ,/J-unsaturated ester 119 which was reduced to allyl alcohol 120906. Allyl vinyl ether 121 underwent a rhodium-catalyzed Claisen rearrangement to afford 7r,13r-dimethyl-l,4-dioxa-(8rC9)-dispiro[4.2.4.2]tetradecan-10-one (122) in 36% yield. 

Studies directed toward the synthesis of bicyclomycin have resulted in the discovery of efficient routes to the construction of the 2-oxa-8,10-diazabicyclo[4.2.2]decane system (160). Thus, the monolactim ether (155) with a hydroxypropyl side chain at position 3, on oxidation with 2,3-dichloro-5,6-dicyano-l,4-benzoquinone (DDQ), gave the product (156) in good yield, presumably via an iminium species (Scheme 51). No trace of the spiro compound (157) could be detected in this reaction. The formation of (156) is probably kinetically controlled. Prior protection of the alcohol as a silyl ether, followed by DDQ oxidation, gave the pyrazinone (158) subsequent deprotection and acid treatment gave the thermodynamically preferred spiro compound (159). The method has been extended to the synthesis of (160), having an exocyclic methylene this compound is a key intermediate in the total synthesis of bicyclomycin [88JCS(P1)2585]. 

Wichmann, J., Adam, G., ROver, S., Hennig, M., Scaione, M., Cesura, A.M., Dautzenberg, F.M., Jenck, F. Synthesis of (1S,3aS)-8-(2,3,3a,4,5,6-hexahydro-1H-phenalen-1-yl) -1-phenyi-1,3,8-triaza-spiro[4.5]decan-4-one, a potent and selective orphanin FQ (OFQ) receptor agonists with anxiolytic-like properties, Eur. J. Med. Chem. 2000, 35, 839-851. 

An excellent review of the isolation, structural elucidation, total synthesis, and postulated biosynthesis of sesquiterpenoids based on the spiro[4,5]decane (vetis-pirane) skeleton has been published." Further studies on the development of alternative routes to the vetispirane sesquiterpenoids have been described. In one report100 the spirocyclic acetal (217), previously used as an intermediate in the synthesis of (—)-a-acorenol (218),101,102 has been converted into (—)-agarospirol (219) and (-)-/3-vetivone (220) by the reaction sequence outlined in Scheme 26. 

Banks, M. R., Cadogan, J. I. G., Gosney, I., Grant, K. J., Hodgson, P. K. G., Thorburn, P. Synthesis of enantiomerically pure (5S)-4-aza-2-oxa-6,6-dimethyl-7,10-methylene-5-spiro[4.5]decan-3-one, a novel chiral oxazolidin-2-one from (-)-camphene for use as a recyclable chiral auxiliary in asymmetric transformations. Heterocycles 1994, 37,199-206. 

Kuroda, C.. and Hirono. Y. Synthesis of spiro[4.5]decane ring system through allylsilane promoted spiroannulation, Tetrahedron Lett., 35, 6895, 1994. 

On the basis of both synthetic and degradative studies, Marshall and co-workers have shown that the structure of -vetivone based on a bicyclo-[5,3,0]decane skeleton is untenable and subsequent work dictated the structure (326) incorporating a spiro[4,5]decane skeleton, and this they have confirmed by total synthesis. The method employed was the selective introduction of an isopropylidene group in a stepwise fashion starting with the keto-olefin (327), which was obtained via photolysis of the known dienone (328). 

The photocyclization of the enone (7) to yield (8) has been used as an approach to the synthesis of the spiro(4,5)decane system. The tetracyclic product (9a) is obtained from the photo-induced intramolecular cyclization of the pyridone (10a) Increase in the chain length involving (10b) resulted in the formation of... 

A new strategy for the synthesis of spiro[4,5]decane sesquiterpenoids has been developed which relies upon the activating and meta-directing effects of the tricarbonylchromium group in 7r-anisoletricarbonylchromium complexes with cyano-stabilized nucleophiles. This new methodology is nicely illustrated in the synthesis of acorenone (175) and acorenone B (176), which combine both inter- and intra-molecular variants of the process (Scheme 21). 

Li, J.-T., Zhai, X.-L. and Chen, G.-F. 2010c. Ultrasound promoted one-pot synthesis of 3-aza-6,10-diaryl-2-oxa-spiro[4.5]decane-l,4,8-trione. Ultrason. Sonochem. 17 356-358. 

The synthesis of l-oxa-3,8-diazospiro[4,5]decan-2-ones 749 from 4-pyridones by addition of trimethylsilyl cyanide, reduction with LAH, and cyclization of the thus obtained amino alcohol with triphosgene has been reported [538]. l-Oxa-3,8-diazo-spiro[4,5]decan-2-ones are structurally related to the antihypertensive agent Indor-amine, a known postsynaptic ai adrenoceptor blocker. 

The synthesis of (+ )-sesquifenchene (450) and of ( )-epi-P-santalene (451) from the common intermediate (449), derived from endo-dicyclopentadiene, has been detailed. Conversion of (449) into the precursor of (450) makes use of the skeletal rearrangement that occurs during solvolysis of active 2-norbornyl esters. In a synthesis of (-H )-hinesol (452) and 10-epi-(-l-)-hinesol, interesting use has been made of a fragmentation reaction.The tosyl derivative (453), which was obtained in several steps from ( —)-P-pinene, was converted into the spiro[4,5]decane (455) on treatment with sodium hydride in DMSO the essential stereoelectronic changes are summarized in the intermediate (454). 

The synthesis of agarospirol (epihinesol) portrays an efficient stereoselective approach to spiro[4-5] decanes based on the intramolecular keto-carbene insertion reaction (A— B) and cleavage of the derived cyclopropyl alcohol (C) to give a spiroketone. 

Recently Yamada et afi described a facile method of preparing the properly functionalized spiro[4-5] decane system by acid catalyzed cyclization of cyclohexenone derivatives, and applied it to the synthesis of / -vetivone. The clever use of proximity effects is a noteworthy feature of this ingenious synthesis. 

Another approach to the spiro[4-5] decane skeleton is illustrated by the exceptionally simple stereospecific synthesis of /3-vetivone based on a novel spiroannelation reaction of cyclic 1,3-diketone enol ethers developed at Columbia. ... 

For a route to spiro[4-5] decanes based on intramolecular keto-carbene insertion in substituted cyclohexenes, see M. Mongrain, J. LaFontaine, A. Belanger and P. Deslongchamps, Canad. j. Chem., 48, 3273 (1970) and P. M. McCurry, Tetrahedron Lett., 1845 (1971). An interesting synthesis of spiro systems by o, a annelation of enamines has been developed by D. J. Dunham and R. G. Lawton, J. Amer. Chem. Soc., 93, 2074 (1971). 

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