2,3-allenol derivative

Although the iron-catalyzed synthesis of allenes from propargylic halides was reported by Pasto and coworkers in 1978 [67], little progress was achieved in this field until recently [68]. In 2003, Fiirstner and coworkers discovered propargylic epoxides as valuable substrates for the reaction with Grignard reagents in presence of catalytic amounts of Fe(acac)3 to generate 2,3-allenol derivatives (Scheme 5.24) [69]. 

Scheme 5.24 Synthesis of 2,3-allenol derivatives developed by Furstner and coworkers.

Fiirstner, A. Mendez, M. Iron-catalyzed crosscoupling reactions efficient synthesis of 2,3-allenol derivatives. Angew. Chem. Int. Ed. 2003, 42, 5355-5357. 

When MOM protected y-allenol derivatives 188a and 188b were used as starting materials for the Auln-catalyzed cycloisomerization, the 5-exo mode was... 

An interesting SN2 -syn addition of Grignard reagents to propargyl epoxides in the presence of Fe(acac)3 was reported by Fiirstner and Mendez (Scheme 7.19) [26], Based on earlier results from Pasto and coworkers [27], the method was developed into a powerful tool for the synthesis of optically active allenol derivatives. The... 

ALLENOLS DERIVED FROM NUCLEIC ACID BASES A NEW CLASS OF ANTI-HIV AGENTS CHEMISTRY AND BIOLOGICAL ACTIVITY... 

Scheme 72 [3,3] Sigmatropic rearrangement of a-allenol derivatives into 2-oxygenated dienes...

Friesen et al. reported that 2,3-allenols 340 can be converted to the corresponding carbamate derivatives 343, in which the terminal C=C bond of the allene moiety can be iodinated to afford diiodides 344. Under the catalysis by an Ag+ salt, compounds 344 react to give iminocarbonates 345 and oxazolindinones 346, leading to diols 347 and amino alcohols 348, respectively, after hydrolysis (Scheme 10.138) [160-162], A similar reaction was observed with trichloroacetimidates 350 [163],... 

Phosphine-catalysed annulation between aldehydes (RCHO) and ethyl allenolate (H2C=C=CHC02Et) gives 6-substituted 2-pyrones (52), proceeding via a zwitterionic (g) enolate.201 The product is derived from the -intermediate, which is favoured by the use of sterically demanding trialkylphosphines, such as tri(cyclopentyl). However, overdoing the phosphine bulk with, for example, the tri(r-butyl) derivative gives no yield. 

Allylindation of allenols also undergoes regio- and stereoselectively to afford 2,6-heptadien-l-ol derivatives via a hydroxy-chelated bicylic transition state (Scheme 74 and Table 13).292 The geometry of the carbon-carbon double bond in the products is E. 

Reactions of 2,3-allenols and their derivatives, particularly those leading to O-heterocycles 06CJO1468. 

By applying a new mode of cooperative catalysis involving the combination of a chiral Bronsted acid and a -symmetric biaryl saturated imidazolium precatalyst, Lee and Scheldt disclosed a highly enantioselective NHC-cata-lyzed [3 + 2] annulation reaction between a,p-alkynals and a-keto esters to generate the desired y-crotonolactones in high yields and excellent levels of enantioselectivity (up to 92% yield, 92% ee). The authors proposed that NHC-bound allenolate underwent addition to the a-keto ester activated by the chiral Bronsted acid derived co-catalyst (Scheme 7.43). 

Alcaide and Almendros have developed a novel palladium-catalyzed domino heterocyclization/cross-coupling reaction of various a-allenols and MBH acetates, furnishing [(2,5-dihydrofuran-3-yl)methyl]acrylate derivatives 489 and 490 and the acrylonitrile 491 in moderate to good yields (Scheme 3.216). " Ozonolysis of MBH adducts originating from aromatic aldehydes provides a-ketoesters 492 with different substitution patterns on the aromatic ring. Diastereoselective reduction of the a-ketoesters 492 affords the corresponding a,p-dihydroxy-esters 493 with excellent anti diastereoselectivity. This method provides an alternative approach for the synthesis of either a-ketoesters or a,p-dihydroxy esters (Scheme 3.217). ... 

Marek and co-workers found that magnesium-to-zinc transmetalation of the alkoxides derived from addition of acetylenic Grignard reagents to acyl silanes promoted the 1,2-Brook rearrangement. The resulting propargyl zinc intermediates (e.g., 37), in equilibrium with the silyl allenol ethers of type 38, underwent diastereoselective carbocyclization in suitable systems, providing cyclopentanol 39, for example, after acid quench and desilylation. ... 

The cycloisomerization of various skeletons via carbenoid intermediates has been achieved under transition metal-catalysis. Bis-nucleophilic propargyl ethers (88), ° as well as indole-based allenols (91), ° have been shown to be appropriate substrates for cycloisomerization under Pt(II)-catalysis, respectively furnishing bis-heterocyclic systems (89) and carbazole derivatives (92). While the formation of bis-heterocycles (89) mainly relies on the reactivity of the a, -unsaturated carbene (90) as key intermediate, the cyclization of (91) to carbazoles (92) has been suggested to proceed via (93) as the key carbene intermediate. Similarly to substrates (91), allenols (94) have been successfully cycloisomerized under Au(I)-catalysis, thus resulting in the formation of... 

Acetylene - allene isomerization of butynols 10a, 10c and lOd must be conducted under a strict control of reaction conditions to minimize side reactions. Thus, employing 1 M instead of 0.1 M NaOH led to formation of a different set of products - oxacyclo-pentenes 16a, 16c and 16d isolated in 17 - 38% yields (Scheme 1). It is likely that allenols 11a, 11c and lid are intermediates in this transformation. Thus, in a stronger base (1 M NaOH), ionization of the primary alcohol can provide a mwe effective driving force for cyclization. The reaction is an interesting example of how an q>en-chain derivative can be transformed in a simple fashion to a nucleoside-like compound. The molecular models indicate that a direct cyclization of 11a, 11c or lid is strongly disfavored. More probably, oxiranes 17a, 17c and 17d are formed first, and the formation of an oxacyclopentene skeleton of 16a, 16c and 16d is then the result of a [1,3] sigmatropic shift.32... 

S. Phadtare and J. Zemlicka, Nucleic acid derived allenols Unusual analogues of nuc-... 

In contrast, a Heck type of reaction will take place if a, P-unsaturated ester is used as the trapping reagent for vinylpalladium intermediates. For example, Alcaide et al. discovered a Pd-catalyzed cascade regioselective spirocyclization of a-allenols cross-coupling via oxopalladation and Heck reaction. Sonogashira and Suzuki reaction can also be incorporated in the sequence instead of the Heck reaction, affording the corresponding potentially bioactive spirocyclic lactam derivatives [117] (Scheme 6.90). 

SCHEME 6.95 Cross-coupling between a-allenols and derivatives. 

Selenenylation of the lactam-tethered allenols (54) can proceed either via oxycycliza-tion to produce spirocyclic derivatives (55) or with ring expansion to yield quinolones (56). The actual outcome can be controlled by the choice of the electrophile and the substituent (NPSP = /V-phenylselenophthalimide). ... 

The cyclization of allenols was applied successfully to the synthesis of different natural products (Krause 2007) (—)-isocyclocapiteUine [186], ( )-isochrysotricine [186], and furanomycin derivatives [187]. 

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