Stereospecific dehydrative alkylation of bis-sulfones: synthesis of a lesser tea tortrix pheromone

Abstract

The intraand intermolecular condensation of alcohols with bis-sulfone methylenes, i.e., dehydrative alkylation, using DEAD and PhgP proceeds stereospecifically at room temperature under essentially neutral conditions affording good to excellent yields of alkylation/ annulation products.The classic Mitsunobu condensation2 of an alcohol with a carboxylic acid, mediated by dialkyl azodicarboxylate/ triphenylphosphine, involves the in situ generation of a highly reactive alkoxyphosphonium intermediate3 which undergoes nucleophilic displacement under mild, nearly neutral conditions with virtually complete inversion of configuration at the electrophilic site (eq 1). Numerous PPh3 ro2cn=nco2r HX OPPh3 V ' y (eq 1) X = RC02", RCOS", RN", ArO'JsO; R3S¡0" I", Br", Cl", F, CNT modifications4 of this protocol have extended its utility to other types of nucleophiles, inter alia, thiolacetate, halides, silanols, tosylate, phthalimide, and heterocycles. Our recent observation5 that DEAD/PhsP complex converts 7-nitroalkanols to -nitrocyclopropanes in good to excellent yields represents a rare example of participation by a carbon-centered nucleophile.6 However, all efforts to exploit the latter dehydrative alkylation of nitro paraffins to form larger rings or for intermolecular condensations failed and, thus, prompted us to evaluate other functionalities.7 Herein, we report that bis-sulfones are particularly effective for a wide variety of dehydrative alkylations/annulations8 as summarized in Table I. Cyclizations affording both small-(entries 1 and 2) and medium-sized rings (entry 3) were achieved with equal ease. Likewise, intermolecular alkylative dehydrations proceeded smoothly (entry 4) and, when applied to diols in the presence of excess reagent, provided

Enantioselective Organocatalytic Conjugate Addition of Aldehydes to Vinyl Sulfones and Vinyl Phosphonates as Challenging Michael Acceptors

“…Besides the obvious synthetic utility of the aldehyde moiety, we also considered the transformation of the sulfonyl groups. [36] After suitable reduction and protection of the primary alcohol 31 a as its TBDMS ether 32 a with reten- tion of the optical purity, freshly prepared samarium diiodide, [37,38] efficiently mediated reductive monodesulfonylation of g-gem sulfonyl protected alcohol 32 a to give a potentially nucleophilic reagent 33 a in good yield and with 82 % ee (Scheme 10).…”

A Mitsunobu route to C-glycosides

“…The coupling constant 3 J¼9. 3 Hz between the anomeric proton of 30, centered at 3.46 ppm and the proton on the endocyclic carbon confirmed the b-stereochemistry assigned to the C-galactoside 26. These materials 28-31 represent useful intermediates that can be employed, via further functionalization, in the preparation of more complex C-glycosides.…”

“…Inspired by Falck's report, 3 we investigated the use of bis(phenylsulfonyl)methane (2) as a possible nucleophile in the synthesis of C-glycosides. Thus reaction of 2,3,4,6-tetra-O-benzyl-a-D-glucopyranose (1) with 2 under Mitsunobu conditions with tributylphosphine provided the b-C-glucoside product 3 in 84% yield, using 1.5 equiv of reagents (Scheme 1).…”

“…2 A dehydrative alkylation of bis-sulfones, mediated by the redox couple triphenylphoshine and DEAD, was described by Falck and co-workers. 3 Similarly, a few other examples of carbon nucleophiles employed in C-alkylation under Mitsunobu conditions have been reported. 4 The chain elongation of primary alcohols of carbohydrates employing bis(2,2,2-trifluoroethyl)-malonate as a nucleophile under Mitsunobu conditions was described.…”

Spirastrellolide studies. Synthesis of the C(1)–C(25) southern hemispheres of spirastrellolides A and B, exploiting anion relay chemistry

“…Turning to the introduction of the C(14) methyl, substituent, Mitsunobu alkylation15 with bis(phenylsulfonyl)-methane proceeded smoothly, leading to bis -sulfone (+)- 42 , which was then fully reduced with LiDBB at −78 °C, employing t -BuOH as the proton source to furnish diol (+)- 43 15. Final application of the Fraser-Reid protocol8 on (+)- 43 completed construction of (−)- 7 , the C(10)–C(22) fragment of spirastrellolide A ( 1 ).…”