Synthesis of Coleon U

The recent publication by Matsumoto¹ of a synthesis of Coleon U²(1) prompts us to present our own preparation of this poly-hydroxy diterpene as the tri-O-methyl (12a) and tetra-O-methyl ethers (12b). In a previous communication³ we outlined our approach which is aimed at several similar natural products such as Coleon C⁴ (1b), Lycoxanthol⁵ (2), etc. and differs considerably from that of the Japanese group. Formally at least, the two syntheses start with the same material, (+) ferruginol methyl ether 5a. In our case the latter was prepared by recorded methods from methyl O-methyl podocarpate after introducing the iso-propyl sidechain⁶ (→4), transforming the C.4 methoxycarbonyl residue to a methyl⁷ (→5a, ferruginol methyl ether) which was oxidised at the benzylic position of the B ring to give sugiol methyl ether 5b.     

Convenient Synthesis of 2-Vinylindoles

A convenient, two-step synthesis of 2-vinylindoles is described from the easily accessible (E)-ethyl-α-allyl-2-nitrocinnamates. Ethylcinnamates (1a and 1b) on reaction with triethylphosphite provide ethyl-2-allylindole-3carboxylates (2a and 2b ) along with minor amounts of their N-ethoxyderivatives (4a and 4b). Alkaline hydrolysis of 2a and 2b provide (E)-2-vinylindoles 3a and 3b in 60 and 67% yield respectively.     

A Convenient Synthesis of 2,3-Diphenyl-2-cyanooxiranes

Several studies¹ have been reported on the synthesis of 2,3-diphenyl-2-cyanooxiranes. Kohler and Brown^la synthesized the oxirane in ca. 30% yield by reaction of desyl chloride with potassium cyanide in aqueous alcohol. However, the method which they employed seems to be rather complicated. Such reaction of desyl bromide with cyanide ion has not been studied in detail. We now report that cis- and trans-2,3-diphenyl-2-cyanooxiranes (2a-d and 3a-d) are conveniently obtained in good yields by reaction of 4′-substituted desyl bromide (1a-d) with 40% aqueous potassium cyanide in a mixture of dichloromethane and triethylbenzylammonium chloride (TEBAC); the total yield of 2c and 3c, for example, was as high as 86%. When cethyltriethylammonium bromide was used as a     

A New Synthesis of 2-Arylbenzothiazoles from 1,2,3-Benzodithiazole-2-Oxides

The reaction of 6-substituted-1,2,3-benzodithiazole-2-oxides (3a-3d) with aromatic aldehydes, carboxylic acids, and their chlorides in the presence of an organic base provides a new method for the synthesis of 6-substituted-2-arylbenzothiazoles (4a-4d) without involving the preparation of intermediate 2-aminobenzenethiols.     

Synthesis of γ-Lactone of 1R-CIS 2,2-Dimethyl-3-(2,2,2-tribromo-1-hydroxyethyl)cyclopropane Carboxylic Acid,A Key Intermediate for Deltamethrin,From (+)-3-Carene

1R-cis-2,2-Dimethyl-3-(2,2-dibromovinyl)cyclopropane carboxylic acid¹ (1), the acid moiety of the highly potent photostable pyrethroid deltamethrin (2) has been obtained either by a Wittig reaction on 1R-cis-caronaldehyde ester (3) employing 1, 1-dibromomethylenetriphenylphosphorane or from the bicyclic tribromo-lactone^2,3 (4) by reaction with zinc and acetic acid. Lactone (4) is thus an important intermediate in the deltamethrin synthesis.     

A General Synthesis of 2-Methoxy-2-Cyclohexenones

The preparation of octalinone 1 at an early stage of a recent synthesis of valeranone¹ required the use of a Robinson annelation with 1,4-dimethoxy-2-butanone (2a), a methoxymethyl vinyl ketone (3) equivalent. The following syntheses of 2-methoxy-2-cyclohexenones illustrate further examples of the heretofore unexploited reaction.²     

Useful Synthesis of Coumestans

A convenient synthesis of coumestans involving a combination of lithiation and Wittig reactions is described. Compounds 1a and 1b on reaction with n-butyllithium followed by treatment with diethyloxalate provide ketoesters 3a and 3b. Reaction of 3(a-b) with phosphorane generated from salt 4 gives 5(a-b) which on reaction with pyridine hydrochloride yield 7(a-b). DDQ oxidation of 7(a-b) gives coumestans 8(a-b).     

An Improved Synthesis of 2′-Hydroxy-3′,4′,6′-trimethoxyacylophenones

A wide variety of 2′-hydroxypolymethoxyacetophenones and propiophenones, e.g. 1a and 1b are used in the synthesis of flavone and ehromone natural products.¹ Repeated attempts to prepare 1a and 1b by reacting 1,2,3,5-tetramethoxybenzene 2 with acetyl or propionyl chlorides and AlCl₃ in ether² gave products which were difficult to purify.³ We traced the problem to ring-ethoxy contaminants which were isolated and tentatively identified as 3a and 3b.     

Total Synthesis of (±) Flavipucine

In 1972 we proposed¹ structure 3 for flavipucine, an antibiotic from an Aspergillus flavipes strain. Later we reported² a novel reaction of 6-methyl-4-hydroxy-2-pyridone with α keto aldehydes which provided 1a from isobutylglyoxal and it was stated that we believed 1a would serve as a key intermediate in the total synthesis of flavipucine 3.     

A Convenient Synthesis of 5-Bromo-2-Pentanone

During a series of studies aimed at the total synthesis of pentacyclic triterpenes¹ we have examined the reaction of enollactones of type 1 with a variety of Grignard reagents. ^1c,2 In one of our problems we required the organometallic reagent 2a derived from the title compound 2b. A previous literature report for the preparation of this compound involved the reaction of α-acetylbutyrolactone 3 with aqueous HBr followed by steam distillation.³ In our hands the yields of 2b via this route were non-reproducible and at best, less than 15%.     

The Synthesis of 4,5-Acetylenic Prostaglandins

The synthesis of cis-Δ⁴ prostaglandins has been reported.¹ The conversion of these Δ⁴ analogs to 4,5-acetylenic prostaglandins can be accomplished via the bromination-dehydrobromination procedure reported earlier.² A new approach to the synthesis of 4,5-acetylenic prostaglandins via readily available intermediate has been developed. We wish to report herein this general approach.³     

An Unusual Aminal Derivative from a Misdirected Gabriel Synthesis

N-(2-Bromoethyl)phthalimide (1) was reacted with sodium imidazolate in DMF to give the novel aminal N-[1-(1H-imidazol-1-yl)ethyl]phthalimide (4a) as well as N-vinylphthalimide (3) and the desired Gabriel intermediate 2. Aminal 4a as well as heterologues 4b - d form directly from reaction of 3 with the appropriate heterocyclic sodium salt.     

A Facile Synthesis of Tetracycles of the γ-Lycorane Type

When an attempted application of the general scheme of alkaloid synthesis, based on the partial hydrogenation of 1 -alkyl-3-acylpyridinium salts and acid-induced cyclization of the resultant 2-piperideines,² to the construction of an Amaryllidaceae alkaloid system failed in the cyclization step, i.e. the transformation of dihydroisoquinoline 4a (prepared by the treatment of ester 2a ³ with 5-bromo-2 -pentanone ethylene ketal, followed by hydrogenation of the salt over palladium-charcoal) into a tricyclic ketal ester,⁴ an alternate, route of synthesis still utilizing a previously prepared isoquinoline precursor (3b) was investigated. The initial observation of the easy conversion of 3b into N-methyl (1a) and O-ethyl products (2b) was helpful in this connection.     

The Synthesis of Ethyl 5-Vinyl-2-Quinuclidine Carboxylate

The synthesis of the minor indolic cinchona alkaloid, cinchonexine (1), from ethyl-5-vinyl-2-quinuclidine carboxylate (2) was reported in 1958¹ but the preparation of 2 was not described until several years later². No further reports on this problem have since appeared. Since 2 was previously obtained in very poor yield from the Beckmann rearrangement of quininene oxine² a more direct approach to its preparation was initiated in order to complete the total synthesis of cinchonexine from synthetically available precursors. Maroquinine (3a) which not only has been prepared in both racemic ³ and optically active^3b forms but is also readily available from quinine⁴ was selected as the starting material fro this synthetic sequence.     

Preparation and Pyrolysis of Cyclooctyl Phenyl Sulfoxide

We recently reported a facile synthesis for bicyclo-[n.2.0]alkanediols of the general structure 1. ¹ The recent demonstration² that cis-bicyclo[3.2.0]heptane-1,7-diol(3) can be converted to the novel, highly-strained trans-bicyclo[4.1.0]heptane system increases the interest in this class of compounds. Comparison of our diols with materials used by Paukstelis and Kao in the rearrangement studies² and further work in our laboratory has shown that the diols reported in our initial communication are trans-diols and should be assigned structures 4 and 5.     

Aminohaloborane in Organic Synthesis. V.1 An Aldol-Type Condensation of Acetonitrile and Phenylacetonitrile with Benzaldehydes Using Secondary Aminodichloroborane

3-Phenyl-3-sec-aminopropionitriles (1) are not found in literature. We describe here a simple synthesis of 1 from acetonitriles (2) and benzaldehydes (3) using sec-aminodichloroboranes (4)² and triethylamine (5).     

A Convenient Synthesis of 3-Methoxyphthalic Anhydride

Many antibiotics of the anthracycline family¹ possess structures for which 3-methoxyphthalic anhydride (1) would be a suitable synthon² in a total synthesis. A classic synthesis of (1) has employed 3-nitrophthalic acid³ but, in our hands, proceeded in low overall yield. Recent syntheses have utilized the Diels Alder reaction of dimethyl acetylenedicarboxylate (2) with 1-methoxy-1,3-cyclohexadiene,⁴ 1,4-diacetoxybutadiene,⁵ 2-acetoxyfuran,⁶ 2-methoxyfuran⁷ or furan⁸ to obtain 3-hydroxyphthalic acid or a derivative. We now wish to report a convenient Diels-Alder synthesis of (1) from 3-methoxy-2-pyrone (3).     

A New Synthesis of 3-Aryl-5-Arylmethylene-2(5H)-Furanones

A recent report about the synthesis of di and tri-substituted 2 (5H)-furanones starting from bromoaldehydes and potassium phenyl-acetate¹ prompts us to report our own studies on the preparation of 3-aryl-5-arylmethylene-2 (5H)-furanones (or butenolides) 1. We have earlier reported² a general method for the synthesis of 1 from phenylpropargyl aldehyde, 2 and arylacetic acids. Although several methods have been reported for the synthesis of the parent compound 1 (R = R₁ = Ph)^3–6, these methods have not been extended to other substituted furanones. Saikachi and Taniguchi⁷ prepared 1 (R = 5-nitro-2-thenyl, R₁ = 2-thenyl and 2-furyl) in 16–17% yields.     

Synthesis of Amimoalkaejediphosphonic Acids

Abstract

Recently we have reported the application of N-diisobutylaluminoimines, generated in situ from nitriles and diisobutylaluminium hydride (Dibal-H), for the synthesis of 1-aminoalkanephosphonic acids [l]. In this paper we would like to present our results on the synthesis of 1-aminoalkanediphosphonic acids. Thus, starting from halogenonit-riles 1 (X = F, C1, Br), and following the procedure presented schematically by eqns. 1 and 2, 1^?amino-halogenoalkanephosphonic acids 3A and 1-aminoalkanediphosphonic acids 4A have been obtained in moderate to good yields.     

Synthesis and Some Reactions of 4-Aroyl-3-Chloro-6-p-Tolylpyridazines

4-Aroyl-3-chloro-6-p-tolylpyridazines (3a &b) were prepared by the action of phosphorous oxychloride on (2). (3a &b) react with hydrazine hydrate to give the pyrazolinopyridazines (4a &b) and with hydroxylamine hydrochloride to give the isoxazolopyridazines (7a &b), respectively. (4b) was also synthesized by the action of phosphorous oxychloride on the hydrazone (5). The reaction of (3a &b) with primary amines in boiling ethanol gives (8a-e), while their reaction with primary aromatic amines in the presence of solvent gives the Schiff's bases (9a-c).