William S. Johnson

Biomimetic polyene cyclizations: A review

Abstract It has been shown that certain polyenic substances, having trans olefinic bonds in the 1,5 relationship, can be induced to undergo stereospecific, nonenzymic, cationic cyclization to give polycyclic products with the all trans (“natural”) configuration. These transformations appear to mimic in principle the biogenetic conversion of squalene into polycyclic triterpenoids, e.g., lanosterol. Acetal as well as allylic alcohol functions have proved to be effective initiators for such cyclizations, many of which proceed to a remarkable degree of completion giving mainly totally cyclized products. Thus, it has been possible to convert, in a single step, an open chain tetraenic acetal having no chiral centers, into a tetracyclic product having seven such centers. The process is highly stereoselective giving only two of 64 possible racemates. Methylacetylenic and also styryl end groups are particularly useful cyclization terminators as they provide a means of realizing five-membered ring formation. Systems with these terminators have been developed for effecting the total synthesis of the steroid nucleus in a single step starting from a substrate containing only one ring. The mechanism of these biomimetic as well as of the enzymic cyclizations is open to question, but the balance of the evidence is somewhat in favor of a synchronous process.

Asymmetric synthesis via chiral acetal templates. 7. Further studies on the cyanation reaction. The use of acetals derived from diols with one chiral center

New examples of the cyanation reaction are described, including one that affords the cyanochydrin 8, an intermediate for synthesizing pyrethroid insecticides. Also tile reaction with acetals derived from S-1,3-butanediol has been examined.

Asymmetric synthesis via acetal templates. 12. Highly diastereoselective coupling reactions with a ketene acetal. An efficient, asymmetric synthesis of R-(+)-α-lipoic acid☆

TiCl4 catalyzes the essentially quantitative coupling of chiral acetals 1 with 1-t-butoxy-1-t-butyldimethylsilyloxyethene 2 to generate β-alkoxycarboxylates in which the new asymmetric center is formed with excellent diastereoselection. β-hydroxycarboxylic acids of high ee result from removal of the chiral auxiliary. The procedure has been applied to the synthesis of R-(+)-α-lipoic acid 10.

Asymmetric synthesis via acetal templates. 15. The preparation of enantiomerically pure mevinolin analogs

Abstract An efficient asymmetric synthesis of the hydroxylactone moiety of mevinolin 1 is described. The key step is the TiCl 4 -catalyzed coupling reaction of acetals 3a and 3b derived from (R)-1,3-butanediol with 1,3-bis(trimethylsilyloxy)-1-methoxybuta-1,3-diene 4 to give the δ-alkoxy-β-keto ester 5 .

Asymmetric synthesis via acetal templates. 9. Further studies of the allylation reaction. Preparation of (−)-dihydromyoporone

Abstract A procedure has been developed for the high-yield coupling of chiral acetals 1 with allyltrimethylsilane (2, R′=H) as well as with methallyltrimethylsilane (2,R′=ME) to afford the hydroxy ethers 3 in which the new chiral center is formed highly enantioselectively. Homoallylic alcohols 4 of high ee are produced by removal of the chiral auxiliary.

Asymmetric synthesis via chiral acetal templates. 8. Reactions with organometallic reagents

Abstract The titanium tetrachloride catalyzed coupling of organometallic reagents with chiral acetals 1 is shown to provide a convenient route for the preparation of a variety of chiral alcohols 4 of high optical purity.

Asymmetric Synthesis via Acetal Templates. 14.1 Preparation of Enantiomerically Pure (3S,4S)- and (3S,4R)-Statine Derivatives

Abstract Several (3S,4S)- and (3S,4R)-statine derivatives have been prepared by attack of nucleophiles on crystalline, epimeric N-BOC-lactams 7a and 7b . The key step in the synthesis of the lactams was the TiCl 4 -catalyzed coupling reactions of acetals derived from (R)-1,3-butanediol with allyltrimethylsilane. Several enantiometrically pure (3 S ,4 S - and (3 S , 4 R )-statine derivatives were made by sodium cyanide-catalyzed reaction of nucleophiles with the lactams 3a and 3b which were synthesized by the scheme 1 → 2 → 3 .

The configuration of cevine

Abstract The alkaloid cevine has been shown to have configuration II. The configurations of nine (C3, C4, C5, C9, C10, C12, C14, C17, C25) of the fourteen asymmetric centers were established by earlier work. Hydrogenation of 16-dehydrocevine 3,4-diacetate (XIII) over platinum proceedeb stereoselectively to cevine 3,4-diacetate (XIV). Sodium borohydride reduction of 16-dehydrocevadine-D-orthoacetate-4-acetate (XVII) afforded a mixture of cevadine-D-orthoacetate 4-acetate (XVIII) and 16-epicevadine-D-orthoacetate 4-acetate (XVI). Both XVIII and XVI were submitted to alkaline hydrolysis followed by acid treatment to give cevagenine C-orthoacetate (XX) and 16-epicevagenine-C-orthoacetate (XIX). XIX consumed lead tetraacetate faster than XX, thereby indicating β-orientation for the C16 hydroxyl of cevine. Arguments are presented for assignment of configurations at C8, C13 and C20. Oxdiation of veracevine-D-orthoacetate triacetate (XXII) with N-bromosuccinimide gave a bridged oxide (XXIII) which, in turn, afforded a formamido ketone (XXIV) on chromic anhydride-pyridine oxidation. The bridged β-oriented oxide structure of XXIII requires that the hydrogen at C22 be α-oriented.

RADIATION‐ENHANCED DIFFUSION OF BORON IN SILICON

Boron was predeposited in silicon substrates by conventional diffusion techniques and then redistributed by bombarding the substrates with 10‐ and 50‐keV protons. The substrates were held at a fixed temperature in the range 500 to 700°C for the duration of the bombardment. The resulting impurity profiles were determined. The low‐energy impurity profiles are characterized by very abrupt junctions while the high‐energy impurity profiles are characterized by long tails. No variation of either the 10‐ or the 50‐keV impurity profiles with temperature was seen over the range given above.

Epoxide-initiated cationic polyene cyclisations

The Lewis acid (2-propoxy)titanium trichloride is an efficient reagent for epoxide-initiated polyene cyclisations. Thus, 4 underwent tricyclisation to yield tricyclic products 5–7 in 73 % yield. The tetraene epoxide 1 gave pentacycle 15 in 21 % yield. The latter is the first example of a cationic pentacarbocyclisation.