Improved Method for the Synthesis of β-Carbonyl Silyl-1,3-Dithianes by the Double Conjugate Addition of 1,3-Dithiol to Propargylic Carbonyl Compounds

Abstract

Base-mediated double conjugate addition of 1,3-propane dithiol to various silylated propargylic aldehydes and ketones allows for an efficient and scalable synthesis of β-carbonyl silyl-1,3-dithianes.Polyketide-based natural products show a tremendous variety of biological activity and structural diversity, and thus the development of new synthetic methods for their efficient syntheses has been a highly pursued goal in organic chemistry. 1 Most general and effective methods for the construction of typical polyketide motifs include an aldol reaction between enolates and aldehydes, 2 asymmetric allylation and crotylation of aldehydes, 3 and opening of epoxides with 2-lithiodithianes. 4 In our plan to develop a modular approach for the construction of polyketides, we dsunglee@uic.edu. Supporting Information Available: General procedures and characterization data of new compounds. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public Accessdesired to take advantage of the capacity of olefin metathesis. 5 Thus, allylation or a crotylation product derived from bifunctional aldehyde 1 can be directly joined with another polyketide motif without any functional group manipulation. Also, it was envisioned that these processes could be further streamlined by a tandem allylation (crotylation)-epoxide opening via 1,4-Brook rearrangement, further improving the economy of polyketide synthesis (Eq 1). Such a streamlined synthesis can also be envisaged for the corresponding ketones 2 via an asymmetric aldol, 6 Evans-Tishchenko reduction 7 and anion relay chemistry (ARC) 4 sequence (Eq 2). The effectiveness of this concept was amply demonstrated in our recent formal synthesis of cochleamycin A (Scheme 1), 8 where, triethylsilyldithiane aldehyde 1 was converted to the β- Through this streamlined sequence, various polyketide motifs are expected to be synthesized in an unusually effective manner, which, however, is contingent upon a secure supply of carbonyl compounds 1 and 2 (Scheme 2) containing γ,3-dithiane and trialkylsilyl moieties.Conceptually, two general approaches (Path A and B) to these compounds are envisioned, and along these lines, several procedures 10,11,12,13 were already reported in the literature. From the standpoint of substrate scope and functional group tolerance, 11,12 the latter involving a double Michael addition of 1,3-propanedithiol to α,β-acetylenic aldehydes and ketones seems to be most attractive. However, the isolation of a silylated hemiacetal by Ley and coworkers under their base-mediated conjugate addition to silyl-substituted propargylic aldehydes (Eq 3) calls for an alternative procedure for silyl-substituted acetylenic aldehydes. Herein, we report on the development of a general, efficient and scalable method for the synthesis of β-carbonyl silyl-1,3-dithianes (1 and 2) carrying various silyl groups.It was expected that the aldehyde 4 and ketone 6 could be garnered via formylation 14 or acylation 15 of the corresponding silyl acetylides. However,...

(Z)-Selective Enol Triflation of α-Alkoxyacetoaldehydes: Application to Synthesis of (Z)-Allylic Alcohols via Cross-Coupling Reaction and [1,2]-Wittig Rearrangement

“…IR (neat): 3029, , 1104 Ethyl 2-( prop-2-yn-1-yl)oxy)acetate. To a solution of 3-(triisopropylsilyl)prop-2-yn-1-ol 29 (3.19 g, 15 mmol) and HMPA (10.4 mL, 60 mmol) in THF (15 mL) was added MeMgBr (15 mL of 1.0 M solution in THF, 15 mmol) dropwise at 0 °C under N 2 atmosphere. After 10 min of stirring, ethyl bromoacetate (2.51 g, 15 mmol) in THF (5 mL) was added, and the resulting solution was warmed 50 °C, and stirred for 1 h. The reaction mixture was quenched with a satd aq solution of NaHCO 3 (5 mL).…”

Copper(II)- and Palladium(II)-Catalyzed Enantioselective Claisen Rearrangement of Allyloxy- and Propargyloxy-Indoles to Quaternary Oxindoles and Spirocyclic Lactones

“…CH 3 CN, CH 2 Cl 2 , TMEDA, and toluene were distilled from CaH 2 . The alcohols and some indole precursors − , were prepared following the literature protocols.…”

Transition‐Metal‐Free Synthesis of Enantioenriched Tertiary and Quaternary α‐Chiral Allylsilanes

“…The authors have cited additional references within the Supporting Information. [17][18][19][20][21][22][23][24][25][26][27] Table 2. Optimization of conditions for the preparation of enantioenriched quaternary α-chiral allylsilanes.…”