Bromo-lactones, reaction with

Allyl silanes react with epoxides, in the presence of Bp3-OEt2 to give 2-allyl alcohols. The reaction of a-bromo lactones and CH2=CHCH2Si SiMe3)3 and AIBN leads to the a-allyl lactone. " Benzyl silanes coupled with allyl silanes to give ArCH2—R derivatives in the presence of VO(OEt)Cl2 " and allyltin compounds couple with allyl silanes in the presence of SnCU. " Allyl silanes couple to the a-carbon of amines under photolysis conditions. ... 

As a final example in this section, the mechanistically interesting transformation of a, 3-unsaturated aldehydes containing a chloro or bromo atom in the 3-position into five-membered lactams or lactones is mentioned. In this transformation, which was developed by Riick-Braun and coworkers, an intermediate iron compound is formed by reaction with [C5H5(CO)2Fe]Na, which yields the products either by adding a primary amine and TiCl4 or a metalorganic alkane as RMgX or RLi [483],... 

A number of enantiomerically pure chiral building-blocks, such as 292-294, have been prepared (270,271) by zinc-copper cleavage of 5-bromo-5-deoxy-2,3-0-isopropylidene-D-ribono-1,4-lactone, followed by reduction. Similarly, from the 5-iodo lactone analogue the enoic acid 295 was obtained by reaction with zinc/silver-graphite (272). 

The 2,5-dibromo-2,5-dideoxy-D-xylono-1,4-lactone (6) (Scheme 2) can also be selectively reduced to give 5-bromo-2,5-dideoxy-D-fhreo-pentonolactone (7) by reaction with either aqueous hydrazine as mentioned above, or by consumption of 1 mole of hydrogen [ 14]. Further reaction with hydrogen and Pd/C leads to 3-hydroxypentanoic acid by an initial reductive elimination [15]. Reduction of the primary bromine in these cases can be obtained by means of tributyltin hydride [25] to give 8. 

This reaction has been used mostly to prepare iodo lactones, but bromo lactones and, to a lesser extent, chloro lactones, have also been prepared. In the case of -y.S-unsaturated acids, 5-membered rings (y-lactones) are predominantly formed (as shown above note that Mar-kovnikov s rule is followed), but 6-membered and even 4-membered lactones have also been made by this procedure. Thallium reagents, along with the halogen, have also been used.653 For a method of iodoacetyl addition, see 5-35. 

Only one example of a derivative of this ring system has been reported. This compound, 2,6-dimethyl-3,4-dioxo-2,3,4,6,7,8-hexahydropyridazino[4,3-c]pyridazine 4-(p-bromo-phenylhydrazone) (149), was obtained in the reaction of the lactone (148) with methyl-hydrazine. A proposed mechanism for this unusual reaction is shown (80JHC617). 

An intramolecular reductive addition of a,a-difluoro acetal radicals to olefins in a 5-exo-trig mode has been reported [95TL3531]. The reaction with the corresponding a-bromo-a,a-difluoroacetates gave no cyclized products. This method provides ready access to a,a-difluoro-y-lactones 34 in good yields. 

Reaction of C-5 activated pentonolactones 13) and of 2,7-diactivated heptonolactones lib, 13) with ammonia gave in both cases 6-membered imino sugars by similar formation of epoxide intermediates (Scheme 4). The 6-bromo-2,6-dideoxy-D-anz6z> 0-hexono- 1,4-lactone gave by reaction with ammonia the 7-membered lactam 14) (Scheme 4). 

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. 

Functionalized P-amino-a, -unsaturated lactones, esters and nitriles can be prepared by nucleophilic vinylic substitution of halogen atoms by amines on the corresponding 3-halo-a,3-unsaturated compounds (12), (13) and (15) (Scheme 9). 3-Bromo-2-butenoates ( )-(13) and (Z)-(13) reacted with secondary amines to give ( )-p-aminopropenoates ( )-(14) regardless of the initial stereochemistry, while the reaction with primary amines yielded a mixture of ( )- and (Z)-(14), when R = H, with the latter predominant. In contrast, the substitution of ( )- and (Z)-nitriles, ( )-(15) and (Z)-(15), with second-... 

The aldehyde was then used in an aldol reaction with the anion from 3-isopropylbut-2-enolide. [The lactone was prepared in the following way bromination of 3-methyl-2-butanone under kinetic conditions (-15 °C) afforded the 1-bromo derivative. The bromine was displaced by acetate on refluxing a solution in acetone with anhydrous KOAc. Reaction of the resulting keto-acetate with the anion from triethylphosphonoacetate afforded the desired butenolide in 55% yield.] The anion was generated in tetrahydrofuran from the butenolide and lithium diisopropylamide and was cooled to -78 °C before addition of the aldehyde. The temperature was maintained below -70 °C for 5h and the reaction was quenched with ammonium chloride at this temperature. Under these conditions (kinetic) the 22R23R intermediate (3) was obtained in 65% yield (26). 

Reformatsky reactions between saturated 3-ketones or 4-en-3-ones and a-bromo-y-butyrolactone afford hydroxy-lactones, e.g. (587), which dehydrate to mixtures of exo- and endo-cyclic olefins. 16-En-20-ones and, to a small extent 17-ones, also react with a-bromo-y-butyrolactone but saturated 20-ketones are unreactive. None of a series of such substituted androstane or pregnane lactones showed any significant hormonal activity. Dehydroisoandrosterone failed to undergo Reformatsky reaction with 2-bromo-6,6-dimethyl caprolactone. ... 

As mentioned in Sect. 2.3, Inanaga and co-workers have demonstrated that Barbier-type reactions of organic halides with carbonyl compounds are promoted by addition of HMPA [16]. They reported a mild convenient method for the direct synthesis of lactones from bromo esters and ketones or aldehydes by using a HMPA-promoted Barbier-type reaction with Sml2 (Scheme 13). They also found that the SmI2/THF-HMPA system was highly useful for the generation of... 

---