Lactones spiro

In spite of their intrinsic synthetic potential, addition reactions of metal enolates of non-stabilized esters, amides, and ketones to epoxides are not widely used in the synthesis of complex molecules. Following the seminal work of Danishefsky [64], who introduced the use of Et2AlCl as an efficient catalyst for the reaction, Taylor obtained valuable spiro lactones through the addition reaction of the lithium eno-late of tert-butyl acetate to spiro-epoxides, upon treatment of the corresponding y-... 

Deffieux D, Eabre 1, Courseille C, Quideau S (2002) ElectrochemicaUy induced spiro-lactonization of a-(methoxyphenoxy)alkonoic acids into quinone ketals. J Org Chem 67 4458-4465. 

Crabb and Schofield8 likewise reported formation of a spiro-lactone during the attempted epoxidation of certain benzocydo-... 

The third type of cycloaddition results from the reaction of cyclopropanones with activated olefins. For example, dimethylketene adds to methyl substituted cyclopropanones affording the spiro lactones 153 a—c. 96,n8,i22b) Similarly the ortho ester 154 is formed from 1,1-dimethoxy-ethylene and 2,2-dimethylcyclopropanone 154 dimerizes to 155 upon standing. ng>... 

As Scheme 59 illustrates, the reaction involves the hydrogen-lithium exchange of phenyl isonicotinamide 202, in the presence of H-BuLi 74/LiBr 203, followed by a reaction with ethyl-4-oxocyclohexanecarboxylate 204 to afford the target spiro lactone 201 as a mixture of cis/trans isomers. In the presence of any residual dilithiated intermediate 205, the spiro lactone 201 can undergo a second reaction to afford the by-product 206. Conducting the reaction in a microflow reactor, comprising of static mixers and... 

Scheme 59 Selective synthesis of a spiro lactone derivative 201 achieved using continuous flow methodology.

Table 30 Summary of the results obtained for the continuous flow synthesis of a spiro lactone 201...

Hydroxyalkanoic acids are easily dehydrated to either spiro or fused /3-lactones. Sulfonyl chlorides have been the traditional reagents employed for this transformation <1996S586, 2001CC753>. However, as illustrated in Equation (38) for a cyclization used as part of a synthesis of lactacystin/omuralide (see also Section 2.06.12.4), bis(oxazolidi-none) phosphinyl chloride (BOP-C1) has proven an effective agent for application in sensitive structures note also the selectivity for introduction of the fused (vs. spiro) lactone <2006JOC1220>. 

These reductions can be combined with other transformations as exemplified by cyclopropane 120, which has been converted to the nitrile 122, the spiro lactone 123, and the functionalized spiro tetrahydrofuran 121 61). All products are eventually derived from cyclohexane carbaldehyde. 

The preparation of spiro-lactone intermediates of the current invention is described (1)... 

Benzenesulfenyl chloride can convert unsaturated acids to lactones. The unsaturated acid (7) is treated with benzenesulfenyl chloride, followed by Raney nickel, to afford the y-lactone (8) in excellent overall yield (equation 5). Another acid (9) has been lactonized to produce the spiro- -lactone (10) which rearranges on silica gel to y-lactone (11 equation 6). 8-Lactones have been also prepared using this approach. An additional advantage of this approach is that the phenyl sulfide moiety can be manipulated into a variety of functional groups to facilitate cyclization. In summary, successful cyclization reactions... 

The course of the reaction may be considered to follow either path a or path b. By analogy to the proposed mechanism of formation of the spiro-lactone of dioxindolepropionic acid (XCI — XCIII), the concerted displacement reaction (path a) is preferred to the displacement of a C-bromo atom in a tribromodienone (path b). 

The spiro-ether (tetrahydrofuran) (57) is oxidized by t-butyl chromate to give the spiro-lactone (58). ... 

Irradiation of the 5-hydroxyoestra-l(10),3-dien-2-one (518) in benzene afforded the spiro-lactone (519). ... 

Several steroidal spiro-lactones have been prepared by treatment of a 17-keto-steroid, such as 3jS-acetoxyandrost-5-en-17-one (212), in a Reformatsky reaction with a bromo-ester, which gave an isomeric pair of 17-spiro-lactones, such as (213). Similar results have been obtained in the oestratriene series. 

The synthesis of spiro y-lactones has been extended to the synthesis of spiro -lactones. This one-pot transformation of 1,3-dienes reacted with epoxides, mediated by Rieke magnesium to spiro -lactones in good isolated yields, was recently reported [15]. Much work has been done to elucidate novel synthetic routes for these types of molecules [16]. In particular, -substituted 5-lactones have recently attracted considerable attention, mainly because molecules of this class include many natural products that exhibit substantial biological activity [17]. However, most methods for the synthesis of these molecules require... 

Scheme 6 illustrates a route for the spiro -lactone synthesis from the magnesium complex of l,2-bis(methylene)cyclohexane 2. 

This convenient, one-pot process for the synthesis of spiro -lactones from 1,3-dienes and epoxides, mediated by Rieke magnesium, provides a proficient route to this class of complex organic molecules in good isolated yields. 

The basic nature of methylenetriphenylphosphorane caused D-homoannulation of 17a-acetyloestr-4-en-17/3-ol (294) before effecting a Wittig condensation the mixed 17-methylene-D-homoandrostanes (295) were formed. When the 17/3-OH group was protected by acetylation, an intramolecular Claisen condensation occurred in polar solvents under Wittig conditions, giving the spiro-lactone (296) and a... 

SPIRO LACTONES Allyltrimethylsilyl-zinc chloride. Grignard reagents. 

The spiro-lactone structure of isopropylidene 1,1-cyclopropanedicarboxylates 7 increases the electrophilic character of the cyclopropane ring. When isopropylidene 1,1-cyclopropanedi-carboxylate was heated in aqueous acetone, water was added across the proximal C-C bond of the ring followed by the formation of y-lactone 8 and hydrolysis of the second ester function. The corresponding bicyclo[4.1.0]heptanedicarboxylate reacted in the same fashion to afford the tra 5-lactone as a result of an inversion of configuration upon the nucleophilic attack by water. °... 

The use of Z-ray diffraction to assign structures to unusual steroid derivatives has been briefly reviewed.3 It includes reference to brassinolide (3), a steroidal plant growth hormone. Another unusual product assigned its structure by the X-ray method is the spiro-lactone (4), derived by thallium triacetate oxidation of 5a-cholestane-3,4-dione.4... 

INTERESTING SPIRO LACTONE FRAGMENT OF NEUROPEPTIDE Y (MILLIMETER-SIZE SINGLE-CHANNEL REACTOR)... 

Scheme 10.5 Hydrogen-lithium exchange reaction of phenyl isonicotinamide and subsequent reaction with a ketone to synthesize spiro lactone...

Table 10.1 Synthesis of a spiro lactone in a pilot-scale batch plant...

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