From chloroalkyl esters with

Zinc-copper couples are used in reactions of a Zn derivative of an a-bromoester with an aldehyde or ketone, or even with a-chloroalkyl esters , and in reactions of CH2I2 and Zn in cyclopropane formation from alkenes, CH2I2 and Zn. In the CH2l2-Zn-Cu reactions the organozinc trapped by MejSnX is IZnCH2l, whereas in the CH2l2-Zn dust-MejAl reaction the trapped species is (IZn)2CH2-... 

One of the limitations of (a-chloroalkyl)boronic ester chemistry has been that the chiral directors are difficult to cleave from boron, and boronic esters are inert in some of the useful transformations of trialkylboranes and alkyldihaloboranes. The vigorous conditions that will remove pinanediol from any pinanediol boronic ester, treatment with boron trichloride [12], leave the pinanediol as tarry ruins and with it any sensitive functionality on the boronic ester. The much milder cleavage by transfer of pinanediol or other chiral diol to phenylboronic acid in a two-phase system works well if the boronic acid to be isolated is water soluble [26]. Other cleavage methods include reduction of pinanediol boronic esters with lithium aluminum hydride or alkylation to borinic ester intermediates [73]. 

The reaction of (a-chloroalkyl)boronic esters with silicon tetrachloride does not epimerize (a-chloroalkyl)boron groups. As a test, (S)-DICHED (1-chloropentyl)-boronate (142) with potassium bifluoride was converted into potassium (1-chloro-pentyl)trifluoroborate (143), which was treated with silicon tetrachloride in THF to form (l-chloropentyl)dichloroborane (144). The dichloroborane was converted into the stable pinacol ester 145, which was transesterified to the (R)- and (5)-pinanediol esters 146 and 147, respectively (Scheme 8.33). H NMR spectra of these two di-astereomers differ sufficiently to show that each was pure and free from more than 1-2% of the other. Compound 144 was shown to react readily with diethylzinc followed by base and finally hydrogen peroxide to yield the expected (S)-3-heptanol, but this chemistry awaits further development to achieve efficient synthetic procedures. 

Pentabromodiphenyl Oxide. Pentabromodiphenyl oxide [32534-81-9] (PBDPO) is prepared from diphenyl oxide by bromiaation (36). It is primarily used as a flame retardant for flexible polyurethane foams. For this appHcation PBDPO is sold as a blend with a triaryl phosphate. Its primary benefit ia flexible polyurethanes is superior thermal stabiUty, ie, scorch resistance, compared to chloroalkyl phosphates (see Phosphate esters). 

Isoprene reacts with a-chloroalkyl ethers in the presence of ZnCl in diethyl ether from 0—10°C. For example,a-chloromethyl methyl ether at 10°C gives a 6 1 ratio of the 1,4-adduct, (F)4-chloro-l-methoxy-2-methyl-2-butene, to the 1,2-adduct, 2-chloro-l-methoxy-2-methyl-3-butene. Other a-chloroalkyl ethers react in a similar manner to give predominately the 1,4-addition product. A wide variety of aHyUc chlorides and bromides and a-chloroethers and esters add primarily 1,4- to isoprene in the presence of acid catalysts (8). 

Trichlorotitanium enolates are directly prepared from a ketone, TiCU, and a tertiary amine [122,123] and undergo aldol reactions with aldehydes [124-129], ketones [129], and imines [130,131], Intramolecular condensation with esters is also known [132-137], Although these reactions, based on a titanium enolate [16], which often results in high diastereoselectivity in aldol and related reactions [122], will not be discussed in detail in this article, the success of the alkylation of this titanium enolate with SNl-active electrophiles should be discussed owing to the high Lewis acidity of the metal center [123], Equation (37) shows stereoselective alkylation with an orthoacetate, which is usually inert to alkali metal enolates [138], Aminoalkylation of trichlorotitanium enolates with (a-chloroalkyl)amine has been performed analogously [139,140],... 

The early literature describes examples of elimination reactions of a rather forcing nature which have not been explored further. For example, the elimination of HCl from (2-chloroethyl)phosphonic dichloride occurs over BaCl2 at 330 and dechlorination of (l,2-dichloroethyl)phosphonic diesters occurs on heating with zinc dust. Dehydrochlorination of a (2-chloroalkyl)phosphonic acid occurs on simple pyrolysis but the preferred procedure consists in the treatment of the acid diester with Et3N in warm benzene, a procedure also used for analogous (2-chloroethyl)phosphinic esters ". The dehydro-halogenation of isopropyl (2-haloethyl)phenylphosphinate by a chiral tertiary amine, such as quinine, quinidine, 1 -phenylethylamine or A-methylephedrine, in a less than equivalent quantity, affords an enrichment of one enantiomer of the ethenylphenylphosphinic... 

The interaction of a alk-l-ene and phosphorus pentachloride to form a complex of the general composition RCH=CH2 2PCl5, now recognized as having the phosphonium salt structure 73, has been known for some time. Very many examples are now known of the decomposition of such complexes with SO2 (or in some cases with P40io ) under controlled conditions when the products are (2-chloroalkyl)phosphonic dichlorides (74) or derivatives thereof. The acids from but-l-ene and pent-l-ene hex-l-ene and hept-1-ene and oct-l-ene and dec-l-ene ° have all been reported. The stability of the initial adducts appears to very considerably, and dehydrochlorination may occur readily if the reaction is carried out with insufficient control. Vinyl and isopropenyl esters of carboxylic... 

Although arsinoacetic acid is readily produced from chloroacetic acid and an excess of sodium arsenite, the analogous reaction does not take place with sodium phosphite. Sodium salts of phosphorous and chloroalkyl acids when brought into contact react with a partial conversion of the phosplioms into the quinquevalent state, and, apparently, the production of an unstable ester-like derivative of glycolhc and phosphorous acids which cannot be isolated. Methyl iodide and sodium phosphite yield the readily hydrolysed methyl phosphite unaccompanied by methylphosphimc acid. 

The use of optically pure a-chloroalkyl boronic esters as electrophiles, e.g. the dicyclohexyl boronate 18 obtained from Matteson s elegant methodology [41], lends access to a-alkyl substituted allylboronates (e.g., 19) with very high diastereomeric purity by way of a net inversion of configuration (Equation 9) [42]. Likewise, alkenylmetal fragments react with chiral dichloromethylboronate 20 to afford optically pure a-chloroallylboronates such as 21 (Equation 10) [43]. Subsequent addition of these a-substituted reagents to aldehydes is highly stereoselective. Furthermore, the chloride... 

The first synthesis of an (a-haloalkyl)boronic ester [8], a free radical addition of a tetrahalomethane, was followed by mechanistic studies that indicated the potential for stereospecific alkylation with Grignard reagents via borate intermediates [9], if only there had been a way to obtain asymmetric examples. The discovery of the efficient reaction of (dichloromethyl)lithium with boronic esters to form (a-chloroalkyl)boron-ic esters by insertion of a CHCl group into the B-C bond opened a new opportunity [10]. Boronic esters of pinanediol, prepared from (+)-a-pinene by osmium tetroxide catalyzed oxidation, were soon found to undergo the insertion reaction with a strong asymmetric bias, with diastereomeric selectivities frequently in the 90-95% range [llj. It was subsequently found that anhydrous zinc chloride promotes the reaction and increases diastereoselectivity to as high as 99.5% in some cases [12]. 

A limitation of pinanediol boronic esters (15) results from the difference between the two diastereotopic faces of the trigonal boron atom. The sequential double di-astereodifferentiation observed with chiral directors having C2-symmetry is not possible. Borate anion 16 derived from 15 rearranges to (a-chloroalkyl)boronic esters 17 and 18 in a ratio that usually exceeds 50 1 (Scheme 8.3) [12]. Alkylmetallic reagents attack 17 from the less hindered side to form 19, in which the chloride to be displaced is not in a comparable steric environment to that in 16 (28). The major diastereomer 20 is produced in about the same proportion as its precursor 17 (Scheme 8.3). 

The chiral amino ester 1999, previously used in a synthesis of (—)-indolizi-dine 209B (1876) by Bardou et al. in 1998, was the starting material in the synthesis of both (—)-1876 and (—)-indolizidine 207A (1554) by Back and Nakajima (Scheme 252). The chloroalkyl amine (+)-2000, made in three steps from 1999, reacted readily with the alkynylsulfones 2001 or 2002 to give the unsaturated indolizidines (—)-2003 and (—)-2004, respectively. In this example, the six-membered ring is formed by C-6/C-7 bond formation. Diastereoselective reduction of the conjugated double bond in the... 

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